H-pylori infection and dermatologic diseases (including lymphoma) http://bit.ly/2JXMPF 

Anxiety screening test  http://bit.ly/13xVBV  

helps  "determine whether you might have an anxiety disorder that needs professional attention. This screening measure is not designed to make a diagnosis of an anxiety disorder or take the place of a professional diagnosis or consultation."

Second SCT for lymphoma patients who relapse after autotransplantation?  Freytes CO, Lazarus HM. Bone Marrow Transplant. 2009 Aug 24.  

Primary central nervous system mucosa-associated lymphoid tissue lymphoma: case report and literature review.  Razaq W, Goel A, Amin A, Grossbard ML. Clin Lymphoma Myeloma. 2009 Jun;9(3):E5-9. PMID: 19525185 

Phase I of AR-12, a PDK-1 Inhibitor Targeting the PI3K/Akt Pathway   http://bit.ly/13CT7p  

‘‘America’s Affordable Health Choices Act of 2009’’ H. R. 3200   http://bit.ly/EAPTw 

Financial Management During a Medical Crisis http://bit.ly/LnWLy  

By Linda Foster, MA  Medically reviewed by Cynthia Haines, MD ... When your loved one has a medical crisis, the last thing you want to — or can —  think about is money. Sound financial planning will give everyone peace of mind.  

Autologous transplantation for relapsed or primary refractory peripheral T-cell lymphoma. http://bit.ly/yYvN9 

Technical: How lymphoma cells may become resistant to Rituxan  http://bit.ly/ClWzy 

Transformation of medicine from a 'one size fits all' to one much more narrowly focused. http://bit.ly/3H8TH 
 

Responses to the panobinostat (pan HDAC inhibitor) in refractory Hodgkin Lymphoma  http://bit.ly/11whFy   | Open studies http://bit.ly/1hGznY

Dr. J. Leonard, 2007 audio: Clinical use of radioimmunotherapy 

Access to Investigational Lymphoma or Cancer Drugs Outside of a Clinical Trial (Expanded Access) http://bit.ly/K6Cor 

HOWEVER: "Manufacturers may not always be willing or able to provide access to a drug outside of their clinical trials. Physicians may not always be able to seek expanded access for patients, depending on a patient’s medical history and the risks associated with taking an investigational drug. The physician must determine that the probable risk from the drug is not greater than the probable risk from the disease."

Also See Our Resource on Compassionate Use

When to Consider Clinical Trials for lymphoma? (and other cancers): 
based on clinical circumstances? PAL 

Comment: New clinical practice policy is needed ... indeed it might be unethical to 
not discuss clinical trials in some clinical circumstances? ~ KarlS

Zelenitz, 2007 Treatment strategies for patients with mantle-cell lymphoma

Elements of evidence: C-P-R: Credibility, Plausibility, Reproducibility. http://bit.ly/evidenceCPR 

Comment:  Very nice and easy-to-remember principles, with a familiar example of causality based on reproducibility: "Touching a hot stove burner always results in a burned hand. No matter how frequently you test this causal relationship, the result will be similar."

Experts on Health Care Reform 2009 at http://healthcarereform.nejm.org/ 

"A growing series that currently includes almost 100 Journal articles and online features, a diverse group of authors representing all parts of the health care system and all points of view have wrestled with the issues the country faces. The articles provide thoughtful commentary on universal coverage, comparative-effectiveness research, outcomes research, health information technology, economic challenges and cost containment, and new delivery systems." nejm.org 
 

Why We Need Science: “I saw it with my own eyes” Is Not Enough 

"For many centuries doctors used leeches and lancets to relieve patients of their blood. They KNEW bloodletting worked. Everybody said it did. When you had a fever and the doctor bled you, you got better. Everyone knew of a friend or relative who had been at death’s door until bloodletting cured him. Doctors could recount thousands of successful cases."

Results from a Study of Arzerra (Ofatumumab) in Rituximab Refractory Follicular NHL ad-hoc-news  

Comment: Not impressive but certainly not surprising - since the participants were refractory to the same class of drug (rituxan).  Mindful that in a 10% response rate, 90% did not respond and got only the toxicity ... could have been better off treated differently.   (If we had a biomarker predicting response to ofatumumab in this population .... that would be a horse of a different color!) What remains to be seen is if ofatumumab is equivalent or better than rituxan in previously untreated or once-treated FL patients. My expectation is  that it will be at least equivalent (and this study seems to support that belief), so I do hope it finds a path to approval. I'm not confident this is it ... but perhaps it will succeed for relapsed CLL ~ KarlS

Favorable clinical outcome in patients with small intestinal NHL  
Leuk Lymphoma. 2009 Aug 10:1-7. PMID: 19672778

"... all patients who underwent complete resection of the small intestinal lesion had extremely favorable results. Further studies are warranted to establish optimal therapeutic strategies."

High rate of survival in transformed lymphoma after autologous stem cell transplant: pathologic analysis and comparison with de novo diffuse large  B-cell lymphoma. http://www.ncbi.nlm.nih.gov/pubmed/19672775 

n = 56 "select" patients with transformed lymphoma (25) or de novo DLBCL (25)

Comment: encouraging news given the prognosis of transformed lymphoma, but the study is small (n = 25 transformed) and the participants  were selected by investigators using unspecified criteria ... key factors such as age and having chemo-sensitive disease, untreated/previously treated, etc. were not described in the abstract.

Expert and Fact-based Perspective on Health Care Reform PAL 

Added content: Health Insurance Reform - FACT CHECK whitehouse.gov  

Sponsor reports Positive Phase II Results Using PROCHYMAL™ for the Treatment of Acute Graft vs. Host Disease osiristx.com  pdf 

Phase II study using PROCHYMAL for the treatment of acute Graft vs. Host Disease or GVHD. In the study, 29 of 31, or 94% of evaluable patients responded after receiving two infusions of PROCHYMAL. More significantly, 23 patients, or 74% achieved a complete response, meaning the patients had experienced total clinical resolution of the disease. Currently, PROCHYMAL is being evaluated in a Phase III trial for the treatment of steroid refractory GVHD.

Clinical Trials for Graft versus Host Disease

Allogeneic Transplantation with Reduced Intensity Conditioning (mini): Importance of Histology for Outcome  pubmedcentral.nih.gov 

Biol Blood Marrow Transplant. 2009 (Full text) Philippe Armand, MD, PhD,1 Haesook T. Kim, PhD,2 Vincent T. Ho, MD,1 Corey S. Cutler, MD,1 John Koreth, MD,1 Joseph H. Antin, MD,1 Ann S. LaCasce, MD,1 Eric D. Jacobsen, MD,1 David C. Fisher, MD,1 Jennifer R. Brown, MD, PhD,1 George P. Canellos, MD,1 Arnold S. Freedman, MD,1 Robert J. Soiffer, MD,1 and Edwin P. Alyea, MD1

"These results emphasize the importance of lymphoma histology for patients undergoing RIC SCT, as well as the lack of relevance of donor chimerism for outcome in this patient population"

FDA Final rule for Expanded Access to Investigational Drugs for Treatment Use (PDF - 603KB) 

AND Charging for Investigational Drugs (PDF - 394KB)

Research to Practice - Interviews with Lymphoma Experts (2005-7) researchtopractice.com 

Gemcitabine and Bortezomib in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma clinicaltrials.gov/ 

This phase I/II trial is studying the side effects and best dose of bortezomib when given together with gemcitabine and to see how well they work in treating patients with relapsed or refractory B-cell or T-cell non-Hodgkin's lymphoma.

Follicular Lymphoma: Experimental Vaccine Extends Disease-Free Survival oncology-times.com 

Dr. Levy noted that in the time since patients were recruited, rituximab has added a powerful advantage in improving the treatment of follicular lymphoma. 

There still could be a role for vaccination, but there need to be trials in which the vaccine Is given before and/or after treatment with chemotherapy plus rituximab, he said.

Also needed are methods to produce the vaccine more quickly. Dr. Levy's conclusion: a qualified yes that the trial is a positive result. But, he said, much more work needs to be done.

See also PAL comment

Patients with certain blood cancers [Mantle Cell] eligible for Quick Disability Determination examiner.com 

Cancer cells protected by immune system  sciencedaily.com 

Comment: This item appears to address why immune-boosting has not worked, and would not work as cancer treatment.  A key to using this information will be figuring out how to suppress regulatory t-cell function in a way that's specific to the tumor and does not lead to autoimmune disease.  ~ KarlS

UK study: Rituxan vs. observation in asymptomatic follicular lymphoma ClinicalTrials.gov 

Role of Stem Cell Transplant in the Management of Follicular Lymphoma theoncologist.alphamedpress.org

Orac on Cancer research and clinical trials 

"...  we absolutely can't make any progress against cancer without well-designed clinical trials that accrue enough patients to have the statistical power to tell if a new treatment is working better than the standard of care."

The World Health Organization's ranking of the world's health systems.  photius.com | 
Original report by WHO: PDF 

# 1 = France .... see also Health Care Lessons From France npr.org 

New PAL topic: Types of Protocols: 

Standard  | On Label | Off-label | Off-Protocol | Investigational - Expanded Access | Alternative?

Part of coming to terms with the diagnosis of a lymphoma (or any cancer) is the challenge of understanding the language of our doctors as it relates to our medical choices and even what is covered by insurance and why. 

Lack of Study Volunteers Hobbles Cancer Fight nytimes.com/

Comment:  We wholeheartedly agree... that patient participation in trials is the most significant obstacle to progress ....

Hey Arnie, as per usual I think you're on to something ... fixing the system rather than blaming any of the parties. It could be important to such a system that the compensation not be tied to any recommended investigational protocol,, instead basing it on the appropriateness of the study to the patients diagnosis and clinical circumstance ... we do not want a conflict 
of interest to influence the referral to a study. Do you agree? ~ KarlS

Arnie: It strikes me that a partial solution to the problem of inadequate number of patient volunteers to make clinical trials viable is to realign the financial contingencies oncologists face when attempting to recruit  patients for trials. Instead of being financially punished for their efforts  to recruit volunteers, why not financially reward oncologists IF a patient 
is accepted into a clinical trial. Doctors are the logical focus and source  for patient volunteers, who must meet the study's public criteria for  acceptance into the study. I have to also believe they recognize the need  and value of cancer research. They likely know which of their patients are  best qualified for a study and therefore would be highly probable to be 
accepted. An accepted patient should be remunerative enough to make an  oncologist likely to continue making referrals in the future. The knowledge  gained from the completed trials will hopefully justify the expense  involved. Can it be any more expensive than what pharma [is trying now].

Betsy: Discouraging...depressing....sad. |  First post: Kind of discouraging, isn't it?


See our ongoing project: http://www.lymphomation.org/clinical-trials-participation.htm  ~ KarlS

BiTE Receives European Orphan Drug Designation for Treatment of Acute
Lymphoblastic Leukemia (ALL)  prnewswire.com | About BiTE 

Comment: Good news for ALL patients ... and for ALL of us ... approvals for one indication generally paving the way for broader use for other cancer types that are targeted by the drug. In this case, cd19 is commonly expressed on b-cell lymphomas. ~ KarlS

Testimony of Wendell Potter, Before the U.S. Senate Committee on 
Commerce, Science and Transportation pbs.org  

Most cancer patients try nontraditional treatments ctv.ca 

"Yet they are extremely popular with cancer patients, who crave control over their disease and want to do everything they can to be healthy -- emotional needs that make them vulnerable to clever marketing and deceptive claims."

Antibodies Kill Leukemia, Lymphoma Cells via Lysosomal Toxins oncologystat.com 

Therapeutic effect of CD137 immunomodulation in lymphoma bloodjournal.hematologylibrary.org 

Comment: If ever there was an approach to root for it would be how to prevent immune tolerance of tumor cells following treatment ... T-regs being a suspect in explaining the disappointing results with vaccines to activate immunity against tumors. ~ KarlS

Anti cd137 is already being studied in patients with advanced melanoma, so we should learn from this about any safety issues, which would likely be applicable across cancer types. ~ KarlS

Rituximab monotherapy for primary cutaneous B-cell lymphoma: response and follow-up in 16 patients 
ingentaconnect.com

"On the basis of our results, single-agent treatment with i.v. rituximab appears to be feasible and safe and results in a high rate of durable remissions. Judging from our data, it appears to be an attractive treatment option and should be directly compared with local radiotherapy."

More on FIT study to compare the efficacy and safety of Zevalin consolidation versus no 
further treatment (control) in patients with advanced-stage follicular NHL responsive to first-line chemotherapy  cancerconferences.org .pdf

See page 11 and 12 for details on protocols given prior to Zevalin

Gene linked to increasingly common follicular lymphoma eurekalert.org/ 

"Dr. Brown said individuals who had the A variant were nearly twice as likely to develop follicular lymphoma. ... To reduce the potential for complicating factors, the more than 3,000 samples in the UC Berkeley-TGen study were from individuals who were HIV negative."

Finding & Evaluating Online Medical & Support Information  PDF

a presentation by Karl Schwartz, President, Patients Against Lymphoma

ASCO 2009: Prolonged Rituximab [monotherapy] Extends Remission in Follicular Lymphoma 
medscape.com (free login req.)

"Of the 202 patients enrolled in the study, 151 were randomized. The median age of the patients was 57 years, 85% of the cohort had stage III or IV disease, 50% had bone marrow involvement, and two thirds had been previously treated with chemotherapy. All participants received rituximab at the standard dose of 375 mg/m2 weekly for 4 weeks, and were re-evaluated at week 12. Patients who responded to the therapy or who had stable disease were then randomized to either no further treatment, which was standard at that time (observation group; n = 78), or to 4 additional doses of rituximab given at 2-month intervals (extended-rituximab group; n = 73).   At a median follow-up of 8.9 years, among surviving patients who had been followed for at least 5 years, the median event-free survival (time to progression, relapse, second tumor, or death) was 13 months in the observation group and 24 months in the extended-rituximab group (P = .0012)."

Secondary malignancies after therapy of indolent NHL 
Haematologica 2008 93: 336-338., Jonathan W. Friedberg - full text haematologica.org 

Is it Reputable?  a checklist for judging the credibility of online information  PDF

Bring List -  to foster timely, efficient, coordinated care PDF

Radioimmunotherapy: FIT to be applied?  Randomized study shows improved PFS by 2 yrs in follicular lymphoma when given as consolidation for chemotherapy  Medscape.com ( login req.)

n = The trial compared a single Zevalin treatment with observation in 414 patients with advanced (stage 3 or 4) follicular lymphoma who had achieved partial or complete remission after first-line chemotherapy. The choice of which chemotherapy regimen to use for induction was left to the physicians' discretion, and various combinations were used, including CVP, CHP, fludarabine, chlorambucil, and rituximab.

Comparison of CT, PET, and PET/CT for Staging of Patients with Indolent NHL
full text: pubmedcentral.nih.gov

R-CHOP versus R-CVP in the treatment of follicular lymphoma: a meta-analysis and critical appraisal of current literature  pubmedcentral.nih.gov 

ASCO 2009: Expert Video Perspective on Lymphoma James O. Armitage, MD  medscape.com/ 

Study Suggests New First-line Treatment Option for Follicular Lymphoma cancer.gov 

Updated Phase II Results With Radiolabeled Epratuzumab in Non-Hodgkin's Lymphoma drugs.com 

n = 62 

The overall objective response rate (partial and complete responses) in 62 evaluable patients was 64%, with 49% of patients having a complete response. Both the objective and complete response rates appear to correlate with cumulative doses. In 16 patients unresponsive to last therapy, 75% responded to Y-90 epratuzumab tetraxetan with 56% complete responses. More importantly, responses were seen across all different types of NHL.

Understanding Clinical Trial Design: PDF A Tutorial for Research Advocates

Authored by Jane Perlmutter, PhD
for Research Advocacy Network’s Advocate Institute

Allogeneic stem cell transplantation in children and adolescents with recurrent and refractory Hodgkin's lymphoma Claviez A, Canals C, Dierickx D, Stein J, Badell I, Pession A, Mackinnon S, Slavin S, Dalle JH, Jurado Chacon M, Sarhan M, Wynn RF, Suttorp M, Dini G, Sureda A, Schmitz N. 
Blood. 2009 Jun PMID: 19498021

Background for professionals: Optimal Use of Prognostic Factors in NHL  
asheducation book.hematologyl ibrary.org

Reports and background on novel gene-based immunotherapy, ISF35

Intra-nodal injection of adenovirus encoding recombinant CD40-ligand (Ad-ISF35) in patients with CLL (ASCO 2009). http://www.abstract.asco.org/AbstView_65_33602.html 

Abstract on chemo-sensitizing properties (ASCO 2009):
http://www.abstract.asco.org/AbstView_65_35718.html 

Technical details on ISF35 technology - Patent information: 
http://www.faqs.org/patents/app/20080318886 

ABT-263 activity and safety in patients with relapsed or refractory lymphoid malignancies in particular chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). 
http://www.abstract .asco.org/ AbstView_ 65_30712. html

ABT-263 showed favorable PK and safety profiles with anti-tumor activity in relapsed/refractory CLL/SLL and follicular lymphoma. Identification of optimal dose and schedule for phase II trials continues.

ABT-263 studies recruiting: ClinicalTrials.gov

Comparing R-CHOP 14 and R-CHOP 21 for the treatment of patients with newly diagnosed DLBCL. 

n = 1,080 randomized to CHOP-R x14 (dose dense schedule) vs. CHOP-R 21 day schedule

Comment: Very encouraging overall results: 2-year failure-free survival rate for the entire cohort of 74% .  Important study because of the size (n >1,000) and that it was randomized.  Curious that the protocols compared were not given with an equal number of  rounds? x6 vs. x8.   Small increased trend  in cardiac toxicity with dose dense CHOP-R x 6 - 2% vs 0.4%

The "autophagy pathway" could be a very important nut to crack, so it bears watching. http://www.ncbi.nlm.nih.gov/pubmed/19216910  

This pathway appears to shut down treatment-stressed cells so that they survive in a dormant-like state, or in hypoxic (low oxygen) conditions.  This cell survival pathway might explain resistance to Rituxan http://www.abstract.asco.org/AbstView_65_33619.html  

For technical background on autophagy, Autophagy in Cancer: Good, Bad, or Both?: http://cancerres.aacrjournals.org/cgi/content/full/66/19/9349 

Idiotype vaccine therapy (BiovaxID) in follicular lymphoma in first complete
remission: Phase III clinical trial results.  abstract .asco.org 

n = 234 pts  enrolled; 177 (76%) achieved CR/CRu and were randomized. 
Of 177 randomized pts, 117 maintained CR/CRu ≥ 6 mo per protocol requirement and then received at least one dose of vaccine, 55 relapsed before vaccination, 4 were vaccine manufacturing failures, and 1 violated protocol.

Comment: This report from a controlled study appears to support that idiotype vaccines are active and have the potential to provide meaningful clinical benefit.  However,  this analysis is for a "modified intent-to-treat population" ... representing roughly half of the patients who started in the study, and these outcomes with PACE and vaccine  may not compare well with Rituxan-based chemotherapy, the new standard of care.  So the key going forward will be if the improvement in outcomes can be reproduced following Rituxan-based chemo.  

Progressive multifocal leukoencephalopathy [PML] after Rituxan therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project  bloodjournal.hematologylibrary.org

In conclusion, rituximab administration may increase risks of developing PML, although the absolute risk of developing PML is probably low. As use of rituximab expands to diverse clinical settings, clinicians and patients should be aware of the potential for PML after rituximab therapy. Awareness and reporting of rituximab-associated PML cases to the FDA are essential to improve our understanding of risk factors, natural course, and alternative therapeutic approaches. Despite widespread public health advisories describing 2 patients with SLE and 1 patient with rheumatoid arthritis who were diagnosed with rituximab-associated PML, we identified 22 previously unreported cases associated with lymphoid malignancies and immunologically mediated cytopenias. Early diagnosis of PML will prompt efforts at immune reconstitution, which may be beneficial in improving survival rates. Finally, early diagnosis before irreversible neurologic damage has occurred will be crucial for evaluation of the efficacy of new antiviral treatments.

Efficacy and tolerability of currently available therapies for the mycosis fungoides and Sezary syndrome variants of cutaneous T-cell lymphoma. Whittaker SJ, Foss FM. Cancer Treat Rev. 2007 Apr;33(2):146-60. Epub 2007 Feb 1. Review. PMID: 17275192

Efficacy of lenalidomide (Revlimid) oral monotherapy in relapsed or refractory indolent NHL: 
Final results of NHL-001. abstract.asco.org 

Oral lenalidomide monotherapy can produce durable responses with manageable side effects in relapsed or refractory indolent NHL

Complete remissions with weekly dosing of SGN-35, a novel antibody-drug conjugate (ADC) targeting CD30, in a phase I dose-escalation study in patients with relapsed or refractory Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (sALCL).  abstract.asco.org

SGN-35 was generally well tolerated and induced CRs in 7 of 8 evaluable pts at the two highest doses in heavily pretreated patients. Pivotal trials of this antibody-drug conjugate will initiate in early 2009.

YM155 shows activity in relapsed and refractory DLBCL. abstract.asco.org 

Targets Survivin - inhibitor of apoptosis proteins (IAPs)

Additional Evidence That Antibiotics Are Effective Against Gastric MALT Lymphomas http://patient.cancerconsultants.com 

Rituximab Maintenance for the Treatment of Patients With Follicular Lymphoma: Systematic Review and Meta-analysis of Randomized Trials medscape.com (free login req.)

Phase I Trial of Daily Oral Polyphenon E in Patients With Asymptomatic Rai Stage 0 to II Chronic Lymphocytic Leukemia

http://jco.ascopubs.org/cgi/content/short/JCO.2008.21.1284v1?rss=1

Epigallocatechin-3-gallate (EGCG) was administered using the standard phase I design with three to six patients per dose level (range, 400 to 2,000 mg by mouth twice a day).

The Sponsor and FDA are negotiating an indication statement for ARZERRA (ofatumumab) in the treatment of chronic lymphocytic leukemia (CLL) under the provisions of accelerated approval based on studies that have investigated response rate, a surrogate endpoint for clinical benefit. 

Briefing documents:

Advisory board:
http://www.fda. gov/ohrms/ dockets/ac/ 09/briefing/ 2009-4444b1- 01-FDA.pdf

GSK:
http://www.fda. gov/ohrms/ dockets/ac/ 09/briefing/ 2009-4444b1- 02-GSK.pdf

Wrong Way in the War on Cancer alternet.org  

"The result is that many of the nation’s 30,000 oncologists are engaged in what could be described as an unobserved and uncontrolled science experiment, especially when it comes to treating the 560,000 Americans who die each year from the more than 100 forms of the disease. As these patients’ cancers advance, their physicians try regimens they read about in journals or hear about from colleagues. The outcomes are never gathered. The data is never analyzed. And the findings are never disseminated."

Beyond Monoclonal Antibodies: 
New Therapeutic Agents in Non-Hodgkin's Lymphomas

http://theoncologist.alphamedpress.org/cgi/content/full/14/5/511 

[Rituxan] Linked To Often Fatal Brain Virus [PML] sciencedaily.com

"But concerns about the drug's association with PML first surfaced in 2006 when two patients with lupus developed the illness after taking rituximab and other immunosuppressive treatments."

Study Shows Disruption Of Immune-System Pathway Key Step In Cancer Progression  medicalnewstoday.com  

"Silencing an inter-cell signaling mechanism called the interferon pathway may be one way newly developing cancers gain the upper hand. It may also explain the immune dysfunctions seen in many cancer patients and why cancer immunotherapies are often ineffective."

Two Targeted Therapies (Rituxan and Epratuzumab) Yields Very Good Results in Patients with Aggressive Lymphoma bio-medicine.org/ 

researchers say that adding the targeted therapy epratuzumab to a regimen known as R-CHOP resulted in an overall 12-month survival of 88 percent in 78 patients. While they call that a very good outcome, the researchers were especially encouraged because the survival rate was 85 percent in patients with high-risk disease.

Technical and preclinical: Ribavirin (anti-viral drug) suppresses eIF4E-mediated oncogenic transformation
2004 Dec 15. PMID: 15601771

Ribavirin and its derivatives offer a pharmacologic means to interrupt networks of tumor suppressors and oncogenes that maintain and enhance neoplasia and malignancy.

Vaccine Concept: Recognition of live labeled tumor cells by dendritic cells: a novel approach to immunotherapy of skin cancer. Shurin MR, Potapovich AI, Tyurina YY, Tourkova IL, Shurin GV, Kagan VE.  Cancer Res. 2009 Mar 15;69(6):2487-96. Epub 2009 Mar 10. PMID: 19276376 

Dendritic cells (DC) loaded with tumor antigens from apoptotic/necrotic tumor cells are commonly used as vaccines for cancer therapy. However, the use of dead tumor cells may cause both tolerance and immunity, making the effect of vaccination unpredictable. To deliver live tumor "cargoes" into DC, we developed a new approach based on the "labeling" of tumors with a phospholipid "eat-me" signal, phosphatidylserine.

Highly increased familial risks for specific lymphoma subtypes. 
Goldin LR, Björkholm M, Kristinsson SY, Turesson I, Landgren O. Br J Haematol. 2009 May 4. PMID: 19438470

Relatives were at the highest risk for developing the same lymphoma subtype as the case. DLBCL was increased 10-fold among relatives of DLBCL patients, FL was increased fourfold among relatives of FL patients and HL was increased fourfold among relatives of HL patients. These results imply that germline susceptibility genes are specific to lymphoma subtype.

Home Diet and Exercise May Benefit Long-Term Cancer Survivors oncologystat.com 

A home-based diet and exercise program reduced the rate of functional decline in a study of more than 600 overweight and older cancer survivors, according to a report in the May 13 issue of JAMA. 

Ginger Eases Nausea From Chemo healthday.com  

Participants were randomized to receive either a placebo or one of three doses of ginger supplement: 0.5 grams, 1 gram or 1.5 grams for three days before the start of chemo and three days after for the next two cycles. All also received traditional antiemetic drugs on the first day of treatment.

Placebo-Controlled Phase III Trial of Patient-Specific Immunotherapy With Mitumprotimut-T  (Fav-Id) and Granulocyte-Macrophage Colony-Stimulating Factor After Rituximab in Patients With Follicular Lymphoma.
J Clin Oncol. 2009 May 4 PMID: 19414675

TTP was shorter with mitumprotimut-T/GM-CSF compared with placebo/GM-CSF. This difference was possibly due to the imbalance in FLIPI scores.

Genetic variation in caspase genes and risk of NHL: a pooled analysis of three population-based case-control studies.  Blood. 2009 May 4.  PMID: 19414860

"It is noteworthy that genetic variants in CASP8 were associated with risk of all major NHL subtypes. Our findings suggest that genetic variation in caspases may play an important role in lymphomagenesis."

Late-onset neutropenia (LON) following RCHOP chemotherapy in diffuse large B-cell lymphoma 
Am J Hematol. 2009 Mar 31. PMID: 19415727

"it is reassuring that LON is self-limiting and unassociated with life-threatening infection. A watchful waiting approach is appropriate in majority of patients who develop LON following RCHOP.

Extranodal marginal zone lymphoma of the ocular adnexa bloodjournal.hematologylibrary.org 

"Besides radiotherapy and chemotherapy, a variety of new treatment options have emerged in the management of patients with ocular adnexal MALT lymphoma, especially monoclonal antibody therapy and antibiotic therapy against Chlamydia psittaci, which has been associated with the pathogenesis of ocular adnexal lymphomas in some parts of the world. In this review, we are presenting a state of the art summary on ocular adnexal MALT lymphomas."

Diffuse large B-cell lymphoma: reduced CD20 expression is associated with an inferior survival bloodjournal.hematologylibrary.org 

"In conclusion, we have demonstrated that discordant CD20 expression by FCM (flow cytometry) using diagnostic DLBCL biopsies may be a novel biomarker that could identify a subgroup of high-risk patients treated with R-CHOP. Moreover, this biomarker could be identified using flow cytometry, a technique that is already used in most clinical laboratories.

A Phase I Study of a Bispecific Chain Immunotoxin for the Treatment of CD19(+), CD22 (+) B-Lineage Leukemia or Lymphoma ClinicalTrials.gov 

"Immunotoxins, such as DT2219ARL, can find certain cancer cells and kill them without harming normal cells.

PURPOSE: This phase I trial is studying the side effects and best dose of DT2219ARL immunotoxin in treating patients with B-cell leukemia or lymphoma that has relapsed or not responded to treatment."

PERSPECTIVE: A re-examination of radioimmunotherapy in the treatment of NHL: prospects for dual-targeted antibody/radioantibody therapy Robert M. Sharkey1, Oliver W. Press2, and David M. Goldenberg1  bloodjournal.hematologylibrary.org

Discusses potential of clearing normal b-cells with non-competing antibody to optimize the effect of the radiolabeled antibody - so that all the cd20 receptors are available to the "hot" antibody. Also discusses fractionated dosing to improve safety without compromising efficacy.

Early: Molecular 'Key' To Successful Blood Stem Cell Transplants Discovered sciencedaily.com  

... identified a molecule called S1P that can tell the thymus to "open the gates" and accept more stem cells. "This discovery gives us a handle on determining whether the thymus will be receptive to migrating stem cells," says Ziltener, a professor in the Dept. of Pathology and Laboratory Medicine.

How Should Doctors Break Bad News? parade.com  

"A recent study in the journal Radiology suggests that the waiting period itself can be bad for your health. Researchers measured the level of the stress hormone cortisol in 130 women who were awaiting their breast biopsy results. They found that the levels of cortisol in patients who had not yet received their results after five days were “essentially indistinguishable” from those found in women with an actual diagnosis of breast cancer."

Swine Flu?  Immune-compromised persons should take special precautions to reduce risk of
exposure and contact their doctors should symptoms present.

Here are links to CDC information:

* Things you can do: http://www.cdc.gov/flu/protect/habit...k_internal_003

* Treatment: http://www.cdc.gov/swineflu/recommendations.htm

* Travel: http://wwwn.cdc.gov/travel/contentSwineFluMexico.aspx

* Updates (investigation): http://www.cdc.gov/swineflu/investigation.htm

Spontaneous regression of chronic lymphocytic leukemia: clinical and biologic 
features of 9 cases  bloodjournal.hematologylibrary.org 

We describe 9 CLL patients who underwent a spontaneous clinical regression over an 11-year follow-up, in spite of a residual neoplastic clone detected by flow cytometry.

Study: SAR3419 in Patients With Relapsed or Refractory B-Cell NHL http://clinicaltrials.gov/ct2/show/NCT00539682 

Background on agent: 
"SAR3419 is an immunoconjugate consisting of an anti-CD19 monoclonal antibody conjugated to the maytansinoid DM4, a derivative of the cytotoxic agent maytansine (DM1), with potential antineoplastic activity. Anti-CD19-DM4 conjugate SAR3419 targets the cell surface antigen CD19, found on a number of B-cell-derived cancers. Upon antibody/antigen binding and internalization, the immunoconjugate releases DM4, which binds to tubulin and disrupts microtubule assembly/disassembly dynamics, resulting in inhibition of cell division and cell growth of CD19-expressing tumor cells." Cancer.gov 

AACR 2009: Oncologists Should Recommend Exercise, But Not Supplements medscape.com

there is accumulating evidence to show that it can improve both prognosis and quality of life

Revlimid® Active for Treating Mantle Cell Lymphoma  cancerconsultants.com

n = 15 patients with mantle cell lymphoma who had failed prior therapy, including stem cell transplantation in five. 

The overall response rate was 53% with 20% (n=3) having a complete response. The median duration of response was 14 months, and the median progression-free survival was 5.6 months. Four of the five patients who had failed stem cell transplantation responded.

CLL Aggressiveness May Be Predicted By New Biomarker medicalnewstoday.com 

They found that high levels of a particular enzyme PDE7B) in the blood are an indicator that chronic lymphocytic leukemia (CLL) - the most common form of adult leukemia - will be aggressive and in need of immediate treatment.

Population-based study of autoimmune conditions and the risk of specific
lymphoid malignancies interscience.wiley.com 

n = 44,350 lymphoid malignancy cases .. vs. 122,531 population control.

These results support a mechanism whereby chronic antigenic stimulation leads to lymphoid malignancy.

Strong preclinical validation of Btk as a target in lymphoma was generated using PCI-32765 in a mouse model of B-cell receptor-driven lymphoma and in spontaneous B-cell lymphoma in companion canines. Source: prnewswire.com   

Immune mediated autologous cytotoxicity against hematopoietic precursor cells in patients with myelodysplastic syndrome  haematologica.org pdf  

Baby broccoli appears to control H-pylori (gut bug)'  news.bbc.co.uk/ 

n = 50

In those who ate broccoli sprouts, levels of a marker of H. pylori in human stools called HpSA was cut by over 40%.

NCCN Adds Cutaneous B-Cell Lymphoma Guidelines  oncologystat.com  

allo SCT: CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation.  Blood. 2009 Feb 12;113(7):1581-8. Epub 2008 Oct 30.  PMID: 18974373  

n = Twenty-nine patients with malignancies that were recurrent or progressive after allo-HCT

Three patients with lymphoid malignancy developed objective disease responses following ipilimumab: complete remission (CR) in 2 patients with Hodgkin disease and partial remission (PR) in a patient with refractory mantle cell lymphoma.

aggressive NHL: Pixantrone Combination Regimen Produces High Rates of Complete Remission 
for Patients With Aggressive NHL Who Fail CHOP Therapy  Docguide.com 

n = 64 pts with relapsed aggressive NHL

"These data suggest that in the relapsed setting, substituting pixantrone for doxorubicin can offer patients a high probability of achieving a complete remission not available with standard chemotherapy regimens and underscores the rationale for studying the CPOP regimen versus the CHOP regimen in first-line treatment of aggressive NHL,"

Quiz: Know your nodes: http://www.lymphoma.ca/kyn/en/default.htm 

Technical background: T Lymphocyte Therapy of Cancer PDF  

"The aim of this article is to review the possibilities, limitations and recent clinical experience with this novel anticancer treatment, namely with adoptive immunotherapy using antigen-specific T cells. "

Patient's guide to getting a second opinion  Web

Dr. Rosenbaum, why are second opinions so important?

"There are actually two types of second opinions. The first is when you want a second opinion. You’ve already been given a diagnosis, and treatment is about to start. It’s important to know that rarely does treatment have to start tomorrow. You’d like it to start tomorrow, but at the same time you have time to think it out and get some additional advice because there are many choices in treatment. Should you have surgery first then radiation then chemotherapy? Or should you have chemotherapy first and radiation and then get surgery?

The second type of second opinion is going to a tumor board. Now, most oncologists participate in tumor boards, either locally at their community hospital or at a university hospital where there are radiotherapists, chemotherapists, pathologists, maybe 10 or 20 people all discussing a case, not all agreeing but coming out with a consensus. So those are the two types of second opinions which are possible. And the tumor boards usually do not cost money because they’re a service, although sometimes they do. The second opinions could vary between $300 and $600.

Hepatitis B Testing Urged for Non-Hodgkin's Lymphoma Treatment: Presented at NCCN DocGuide

NCCN: Cutaneous B-Cell Lymphoma Guidelines Debut MedpageToday.com 
 
Primary cutaneous B-cell lymphoma is unlikely to reduce a person's life expectancy, but even with definitive therapy, the disease is likely to recur, doctors said in unveiling new guidelines for treatment of the disease.

About 1,000 to 1,500 cases of cutaneous B-cell lymphoma occur each year in the U.S., said Steven M. Horwitz, M.D., of Memorial-Sloan Kettering Cancer Center in New York and a member of the guideline panel. But because the disease is rarely fatal, there are tens of thousands of people living with it.

Resource: What You Should Know about Pain Management jointcommission.org pdf 

Resource:  Immunization in persons with compromised immunity  cdc.gov 

Resource: Decide for Yourself: A guide to Healthcare Directives: haponline.org pdf 

How Follicular Lymphoma is treated in US: First Report of the National LymphoCare Study.
Friedberg JW, Taylor MD, Cerhan JR, Flowers CR, Dillon H, Farber CM, Rogers ES, Hainsworth JD, Wong EK, Vose JM, Zelenetz AD, Link BK.  J Clin Oncol. 2009 Feb 9. PMID: 19204203 

Initial therapeutic strategy was: observation, 17.7%; rituximab monotherapy, 13.9%; clinical trial 6.1%; radiation therapy, 5.6%; chemotherapy only, 3.2%; chemotherapy plus rituximab, 51.9%. Chemotherapy plus rituximab regimens were: rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone, 55.0%; rituximab plus cyclophosphamide, vincristine, and prednisone, 23.1%; rituximab plus fludarabine based, 15.5%; other, 6.4%.

CNS lymphoma: Is Single-Agent Temozolomide the Treatment of Choice for Recurrent Primary Central Nervous System Lymphoma? medscape.com (free one-time subscription req.)

The authors conclude that in a heavily pretreated population, temozolomide shows potential in the treatment of PCNSL, with modest toxicity. The authors suggest that temozolomide should be further developed as induction, consolidation and maintenance therapy for primary lymphomas.

Drug Dispensary of Hope: Locate by location  dispensaryofhope.org

Physicians' offices, distributors, and manufacturers send their donated medications to the program's distribution center, which receives prescription requests from the dispensing partners and forwards the medications as needed. 

Meta-analysis: Rituximab Should Be Used for Maintenance in Follicular Lymphoma
http://www.medscape.com/viewarticle/588413  (free subscription req.)

Requires confirmation ... peer review.

Please read! One in Five Cancer Clinical Trials Is Published: 
A Terrible Symptom—What's the Diagnosis? theoncologist.alphamedpress.org 

So, while perhaps only one in five cancer clinical trials is ever published,
of those unpublished, a significant percentage probably died for lack of accrual ... See also our related project

A re-examination of radioimmunotherapy in the treatment of non-Hodgkin lymphoma: Prospects for dual-targeted antibody/radioantibody therapy.  PMID: 19182204 

Combining an unconjugated anti-CD20 antibody therapy with a radioimmunoconjugate binding to a non-competing antigen might improve responses by allowing optimal uptake of each agent.

Mechanisms of activity: Rituximab immunotherapy results in the induction of a lymphoma idiotype-specific T-cell response in patients with follicular lymphoma: support for a "vaccinal effect" of rituximab.  PMID:19196657 

We analyzed the response against the immunoglobulin expressed by the FL before and after rituximab monotherapy in five FL patients and found an increase in FL idiotype specific T-cells post-rituximab in 4/5 patients.

Attitude! Are You Going to Finish Strong? Inspiring Video

Experts: Selection from: Assessing the Standard of Care for Indolent Lymphomas / CLL
James O. Armitage, MD Bruce D. Cheson, MD Owen A. O'Connor, MD, PhD

medscape.com/ (one-time, free subscription req.)

Auto SCT vs. CHVP + interferon in untreated follicular lymphoma: Blood 2009 113: 995-1001

n = 172 previously untreated pts with follicular lymphoma, transformed excluded

randomized for either immunochemotherapy or high-dose therapy (HDT) followed by purged ASCT.

Alert: Green Tea May Negate the Effects of a Common Cancer Therapy prnewswire.com/
 
"the team was surprised to find that the EGCG compound seemed to prevent bortezomib (Velcade) from fighting the disease by blocking its proteasome inhibitory function -- the two compounds effectively contradicted one another in the cell, leaving nearly 100 percent of the tumor cells intact. "

Hodgkins outcomes: Increased Progression Free Survival did not lead to improved Overall Survial in
HD2000 trial hemonctoday.com

n = patients with advanced Hodgkin’s lymphoma. All patients underwent radiation treatment after chemotherapy.

Transformation data: Population-based analysis of incidence and outcome of transformed non-Hodgkin's lymphoma.  PMID: 18838711 

n =  600 patients with newly diagnosed FL met the inclusion criteria.

See for detail:  News: About Transformation 

PET SUV and transformation? The majority of transformed lymphomas have high standardized uptake values (SUVs) on positron emission tomography (PET) scanning similar to diffuse large B-cell lymphoma (DLBCL). PMID: 19139176 

n = 40

"CONCLUSIONS: Like de novo aggressive lymphomas, the majority of transformations have a high SUV(study-max) for a given pretreatment staging study, although many do not have very high values. Transformation should be suspected in indolent lymphoma with high SUVs on FDG-PET. Biopsies should be directed to the site of greatest FDG avidity."

orbital MALT: Treatment with the Zevalin(R) Therapeutic Regimen as Sole Therapy Produces 83 Percent Complete Response Rate in Mucosa-Associated Lymphoid Tissue (MALT) Orbital Lymphoma http://news.prnewswire.com  

n = 9 patients with MALT lymphoma of conjunctiva or orbit and 3 patients with low grade follicular lymphoma

Review: Radio-Immunotherapy with Zevalin®: Updates from the 2006 American Society of Hematology Meeting  http://professional.cancerconsultants.com  

Review: CLL diagnosis and prognosis: implications of the IWCLL guidelines
Roger Owen, Haematological Malignancy Diagnostic Service (HMDS)  2009

lymphomaforum.org.uk 

"It is important to recognize that the value of the cellular prognostic markers detailed above is very much determined by the clinical context in which they are demonstrated. "

Commentary on Homeopathy: The side effects of inert "remedies"  PDF 

Biospecimen-based study: Impact of the tumor microenvironment on prognosis in follicular lymphoma is dependent on specific treatment protocols 

http://www.haematologica.org:80/cgi/content/full/94/1/70 

n = Pre-treatment biopsy samples of 61 pts with follicular lymphoma treated in an EORTC/BNLI study

Editorial: Clinicobiological, prognostic and therapeutic implications of the tumor microenvironment in follicular lymphoma 

http://www.haematologica.org/cgi/content/full/94/1/16 

On science-based medicine: Natural versus “natural” in CAMworld  
 
Published by David Gorski under Cancer, Clinical Trials, Science and Medicine 

This is what Swayze said:  If anybody had that cure out there, like so many people swear they do, 
you’d be two things. You’d be very rich, and you’d be very famous. Otherwise, shut up.

Recruiting: Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Cancer This study is currently recruiting participants.

RATIONALE: Giving low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving a monoclonal antibody, such as alemtuzumab, before transplant and tacrolimus and methotrexate after transplant may stop this from happening.

http://clinicaltrials.gov/ct2/show/NCT00818961

Preclinical: Grape Seed Extract Kills Laboratory Leukemia Cells, Proving? Value of Natural Compounds

The real news in this story is how the lead researcher responsibly tempers the interpretation of his 15 October report in Clinical Cancer Research. Grape seed extract 

CLL Flavopiridol Confirmed Active for Treatment of Relapsed CLL with Adverse Cytogenetics 

http://professional.cancerconsultants.com 

n = 62 patients with relapsed CLL treated with flavopiridol...  pretreated with dexamethasone to block the effects of IL-6 release during therapy.

Potential Breakthrough For T-Cell Lymphoma Patients With Drug That Mimics Folic Acid

http://www.sciencedaily.com/releases/2008/12/081209155010.htm 
 
n = 109 patients with peripheral t-cell lymphoma

"These results indicate that pralatrexate produces a major durable response in patients for whom numerous prior treatments have been unsuccessful," says Dr. Owen A. O'Connor

Statin Use and Prognosis in Patients with Follicular and Diffuse Large B Cell Lymphoma

http://ash.confex.com/ash/2008/webprogram/Paper8512.html 

n = 293 newly diagnosed FL patients and 228 newly diagnosed DLBCL patients

Conclusions: Statin therapy does not appear to be associated with inferior clinical outcome in DLBCL treated with rituximab and CHOP or CHOP-like therapy. Therefore direct inhibition of rituximab binding to CD20 may have limited clinical significance or/and may be overcome by inhibitory impact of statins on cell signaling. The latter possibility is supported by our observation that statin use is associated with improved event-free survival in follicular lymphoma. 

CLL outcomes: FCR Versus FC Improves Response Rates and Progression-Free Survival of Previously Untreated [and fit] Patients with Advanced CLL

n = 817 pts with good physical fitness - median CIRS score was 1 (range 0-8), median age was 61 years (range 30 to 81), The overall incidences of trisomy 12 and abnormalities of 13q, 11q23, and 17p13 detected by FISH were 12%, 57%, 25%, and 8%, respectively, with no statistically significant differences between treatment arms.

http://ash.confex.com/ash/2008/webprogram/Paper9237.html

CLL outcomes: Allogeneic Hematopoietic Stem-Cell Transplantation for Chronic Lymphocytic Leukemia With 17p Deletion: A Retrospective European Group for Blood and Marrow Transplantation Analysis 

oncologystat.com 

n = 44, majority of 17p deletions were detected via fluorescence in situ hybridization analysis; the median percentage of deleted cells was 63%. 98% had previously received fludarabine, more than half (60%) had fludarabine- resistant disease. [AGE not specified in abstract] .. participants had median of 3 previous lines of chemotherapy. One third of the patients underwent an auto HSCT; half were not in remission at the time of transplantation. 

NHL outcomes: Sustained Response Duration Seen after Treatment with Single Agent Blinatumomab (BiTE) in the Ongoing Phase I Study in Patients with Relapsed NHL

http://ash.confex. com/ash/2008/ webprogram/ Paper9115. html

n = 39 Relapsed NHL patients requiring treatment were included. Most patients were pre-treated, with a median of 3 previous chemo/immunotherapy regimens.

Travel: Tips for Traveling when you have a cancer cancer.net

CLL/SLL: Flavopiridol Induces Durable Responses in Relapsed CLL Patients with High-Risk Cytogenetic Abnormalities

http://ash.confex.com/ash/2008/webprogram/Paper11242.html

n = 117 pts with relapsed CLL (n=107) or small lymphocytic lymphoma (n=10) , median age 60 years, 116 pts had received prior purine analog therapy, and 85 pts (73%) were refractory to (n=82) or intolerant of purine analog (n=3).  Ninety-three pts were Rai stage III/IV (79%), and 85 pts had bulky lymph nodes ³ 5 cm (73%).

Alert: Some patients taking Rituxan may experience bowel obstruction 

aol.mediresource.com 

"Patients taking Rituxan who experience abdominal pain, especially early in treatment, should contact their physician immediately," Health Canada advised. The average time for patients on the medication to develop bowel perforation was six days from the beginning of therapy."

An Oral Inhibitor of Syk (Fostamatinib Disodium (FosD), Is Well-Tolerated and Has Significant Clinical Activity in DLBCL and SLL/CLL

http://ash.confex.com/ash/2008/webprogram/Paper5094.html 

n = 68 pts with relapsed/ refractory NHL in 3 separate disease cohorts: DLBCL (23); FL (21) and other B-cell NHL (24) including SLL/CLL (11), MCL (9) marginal zone/MALT (3) and lymphoplasmacytic NHL (1).  Median age was 61 (range 41-87); with  median of 5 prior therapies, including ASCT (16; 12 with DLBCL) and radioimmunotherapy (8). 

DLBCL prognosis: Variations in Gene Activity Can Predict the Survival of Patients With DLBC Lymphoma docguide.com 

"Our findings reveal new biological variations in DLBCL that influence whether a patient is likely to be cured by chemotherapy," said Dr. Staudt. "These biological variations are significant in patients treated with the current standard of care, R-CHOP. Our results provide many fresh ideas about how existing drugs might be utilised to overcome the remaining resistance of some DLBCL tumours to our current therapy."

MCL outcomes: Confirmation of the Efficacy and Safety of Lenalidomide Oral Monotherapy in Patients with Relapsed or Refractory Mantle-Cell Lymphoma: Results of An International Study (NHL-003) 

n = 39 relapsed or refractory MCL and measurable disease ≥2 cm after at least 1 prior treatment regimen were eligible. 

http://ash.confex.com/ash/2008/webprogram/Paper13353.html

The ORR with lenalidomide was 
41% (16/39), including 
13% (5/39) complete response (CR)/unconfirmed CR, and 
28% (11/39) partial responses. 
Ten (26%) patients had stable disease. 

Revlimid mechanisms? Direct Inhibitory Effects of Lenalidomide on the Proliferation and VEGF Production of NHL Cells Are Associated with Increased SPARC Expression

http://ash.confex.com/ash/2008/webprogram/Paper10294.html  

n = preclinical

Mechanistic studies indicated that lenalidomide strongly increased the gene expression of the tumor suppressor genes p21cip1 and SPARC to varying degrees.

CLL perspectives Opinions & Reports from Dr. Michael Keating The CLL Treatment Surge

  http://www.cllglobal.org:80/prescorner.htm

For example:  Theme 5 – Stroma CLL Interaction

This concept may prove difficult to fully explain. All CLL cells exist in a matrix of different tissues. There are supporting cells, blood vessel cells, fat cells, and very specific cells which maintain the integrity and survival of the CLL cells. This complex interaction is the reason why CLL cells will last for 100 days in the body but will die in 3 – 6 days when taken out of the body. A number of separate approaches will be used to evaluate how we can modify this matrix to improve CLL therapy.

CNSL outcomes :  Addition of Systemic High-Dose Methotrexate to Intrathecal Chemotherapy for Central Nervous System Prophylaxis Substantially Reduces CNS Recurrence Rates in Patients with at-Risk Aggressive Lymphoma: A Historically Controlled Prospective Study

http://ash.confex.com/ash/2008/webprogram/Paper4036.html

Monday, December 8, 2008

n = 85 pts with newly diagnosed aggressive NHL with CNS risk factors such as multiple extranodal sites and elevated LDH

CLL: Ofatumumab (HuMax-CD20), a Novel CD20 Monoclonal Antibody, Is An Active Treatment for Patients with CLL Refractory to Both Fludarabine and Alemtuzumab or Bulky Fludarabine-Refractory Disease: Results from the Planned Interim Analysis of An International Pivotal Trial

Monday, December 8, 2008: 11:45 AM

http://ash.confex.com/ash/2008/webprogram/Paper5918.htm l

n = 138 previously treated CLL patients (Double refractory, n=59; Bulky fludarabine refractory, n=79

The bottom line here, as I see it anyway, is a next generation rituxan-like antibody with low toxicity was active and achieved responses in this very difficult context: The overall response rate (ORR) to salvage therapy (of any type) for such patients is approximately 20%

For Ofatumumab: the overall response rate was 51% in this study.

Also rituxan monotherapy is not often very effective in CLL even in more favorable circumstances. So this bodes well for Ofatumumab approval I hope, and it could lead to much better outcomes in CLL when Ofatumumab is combined with chemo and used earlier.

Stress: Good tips on managing it  cancer.net 

follicular NHL Bexxar outcomes for first-line treatment, an update webmd.com 

n = 76 previously untreated with follicular NHL.

Results showed that 95% of the patients responded to the treatment; 75% had a complete disappearance of the signs of their cancer. At follow-up, the estimated eight-year overall survival rate was 86%. Fifty percent of patients continued to show no signs of cancer. Of the 57 patients who had a complete remission, two-thirds remained in remission.

follicular lymphoma: Strategies Have Neither Clinical or Survival Benefit Following High-Dose Chemotherapy and Progenitor Cell Rescue in Follicular Lymphoma 

 http://ash.confex.com/ash/2008/webprogram/Paper10156.html  
 
n = Ninety-nine consecutive pts. who received HDT (cyclophosphamide and total body irradiation) with autologous stem cell rescue for recurrent FL 

... annual surveillance investigations do not help to identify pts. that require treatment and do not improve the outcome of this population. They should therefore be abandoned. Time to relapse based on data from pts. on annual surveillance should be interpreted with caution because of the poor correlation with time to next treatment and OS.

Statins Use and Prognosis in Patients with Follicular Lymphoma (FL) and
Diffuse Large B Cell Lymphoma (DLBCL)

n = 393 newly dx FL, and 228 newly dx DLBCL
 
http://ash.confex.com/ash/2008/webprogram/Paper8512.html 

DLBCL: The Role of Radiotherapy to Bulky Disease in the Rituximab Era: Results from Two Prospective Trials of the German High-Grade NHL Study Group for Elderly Patients with DLBCL

http://ash.confex.com/ash/2008/webprogram/Paper11600.html  

n = 166 elderly patients with DLBCL

In the rituximab era additional radiotherapy to bulky disease has no role for elderly patients in CR/CRu after completion of 6xR-CHOP-14 immunochemotherapy, but (unlike 2 additional chemotherapy cycles in the 8xR-CHOP-14 arm of R-CHOP-Rx) appears to be beneficial for patients with bulky disease achieving a PR. 

follicular: Durable Responses in Patients Treated with Galiximab (Anti-CD80) in Combination with Rituximab for Relapsed or Refractory Follicular Lymphoma: Long-Term Follow-up of a Phase II Clinical Trial Saturday, December 6, 2008

http://ash.confex.com/ash/2008/webprogram/Paper6805.html 

n = 64 pt with fNHL, mean age was 59 yrs., least 1 prior lymphoma therapy; 42% were rituximab naïve, rituxan refractory were excluded. FLIPI low (27%),  intermediate (39%), and high (34%).

Patient guidance: Cancer Patients Often Forget Details of Doctor Visit cancerpage.com 

Communicating prognosis requires careful tailoring to individual patient's preferences for more or less information and balancing the needs for clear information while maintaining hope," the researchers write.

RIT consolidation:  Effect of Adding Zevalin Consolidation to Three Cycles of CHOP Plus Involved-Field Radiotherapy for Limited-Stage Aggressive Diffuse B-Cell Lymphoma (SWOG 0313) Dec 8, 2008

http://ash.confex.com/ash/2008/webprogram/Paper4856.html 

n = 40 pts with limited stage DLBCL with least one adverse risk factor (age > 60 years, elevated LDH and a performance status of 2) OR non-bulky stage II disease. 

Estimated 2-year progression-free survival is 91% (95% CI: 81%-100%) and 
2-year OS is  95% (95% CI: 87%-100%). 

Toxicity has been reversible with no treatment related deaths. 

There were 9 grade 3 and 10 grade 4 hematologic events, but only 3 episodes of febrile neutropenia and only one patient requiring platelet support. Other grade 3 toxicities were mostly gastrointestinal symptoms including mucositis and nausea/vomiting or flu-like symptoms. 

We conclude that patients with aggressive histologies of NHL and high-risk LD treated with CHOP(3) plus IFRT followed by Z result in outcome that compares favorably to our historical experience in the short term. 

Longer follow-up will determine whether these patients exhibit a pattern of late recurrences as seen in our prior  experiences. 

Auto SCT with RIT: Radioimmunotherapy (Zevalin®) Combined with BEAM Conditioning Regimen and Autologous Stem Cell Transplantation for the Treatment of NHL ash.confex.com  

n=53, relapsed and refractor (16 follicular, 37 aggressive) , age 65 or less.

In pts with different histology nHL, who failed to achieve CR after previous immuno-chemotherapy, RIT integrated with high-dose chemotherapy (Z-BEAM) is capable to induce  86% of ORR,  74% of CR and  3 ys EFS of 64%, with sustained engraftment and an acceptable extra-haematological toxicity, mainly restricted to pts older then 65 yrs. 

Perspective: Evidence Mounts for the Efficacy of Radioimmunotherapy for B-Cell Lymphomas jco.ascopubs.org   Oliver W. Press  

"Together, these two studies confirm and extend prior data demonstrating the tremendous potential of RIT  for the treatment of B-cell NHL at diagnosis and after relapse at both conventional and myeloablative doses.  Despite the overwhelming body of evidence that has accumulated, however, RIT remains underused  in the United States and other countries. The reasons for this underuse  have been widely debated but seem to be related, at least partially, to logistic issues involved in transfer of care from the hematologist/oncologist to the nuclear medicine  physician, concerns about inadequate reimbursement by Medicare for RIT,  and exaggerated emphasis on delayed effects such as marrow damage and  secondary malignancies. It is hoped that studies such as those in this issue  will encourage wider appreciation and use of RIT."

Drug combination (dexamethasone, cytarabine and carboplatin) for NHL produces fewer side effects
virtualmedicalcentre.com  

n = 25 children who had newly diagnosed non-Hodgkin lymphoma

The researchers’ aim in using the regimen they dubbed “DAC” was to achieve both an improved effectiveness over conventional therapy and to reduce that therapy’s dosage of two anti-cancer drugs—doxorubicin and cyclophosphamide—that are more likely to produce cardiac problems and infertility.

Outcomes fNHL: Phase II Trial of Short-Course CHOP-R Followed by Zevalin and Extended Rituxan in Previously Untreated Follicular Lymphoma. Clin Cancer Res. 2008 Nov 1;14(21):7088-7094. PMID: 18981007 

n = 60 patients with stage II to IV symptomatic or bulky FL from a single institution; 
median follow up was 19.7 months (range, 0.26-35.9 months).

For intent-to-treat analysis, the complete response (CR) rate after CHOP-R, as assessed by CT and PET imaging, was 40% and 46%, respectively. After RIT, the CR rate improved, as assessed by CT and PET imaging, to 82% and 89%, respectively. 

Ten [of 55?]  patients have progressed, including eight from best response of CR.  

Seven of 18 patients who were PET positive after CHOP-R progressed compared with 3 of 37 patients who were PET negative (P = 0.010).

Is it DLBCL or Burkitt's? C-MYC Rearrangements are Frequent in Aggressive Mature B-Cell Lymphoma with Atypical Morphology  ijcep.com  pdf 

"To avoid under- or over-treatment of the patients, it is critical to distinguish Burkitt's lymphoma (BL) from DLBCL when encountering these aggressive mature B-cell lymphomas with atypical morphology. Since diagnosis of BL requires strict criteria (CD10+, BCL6+, close to a 100% proliferation index and IG-MYC), many cases that do not meet all these criteria were diagnosed as DLBCL, and therefore would not receive the benefit of intensified chemotherapy. More recent studies suggest that some of those DLBCL cases indeed had the molecular signatures of BL and over 10% of those molecular BL did not harbor any detectable C-MYC translocations". 

Background: Helping Your Patients Deal with Questionable Cancer Treatments, William Jarvis, Ph.D.

caonline.amcancersoc.org  pdf

Outcomes: High dose therapy followed by autologous purged stem cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: A randomized multicenter study by the GOELAMS. Final results with a median follow-up of nine years. Blood. 2008 Oct 27. PMID: 18955565  

n = 172 patients with untreated FL for either immunochemotherapy or high-dose therapy (HDT) followed by purged ASCT

In conclusion, the occurrence of a PFS plateau suggests that a subgroup of patients might be cured by ASCT. However, the increased rate of secondary malignancies may discourage the use of purged ASCT in combination with TBI as first-line treatment for FL.

Second pathology Evaluations: Comparison of Referring and Final Pathology for Patients With Non-Hodgkin's Lymphoma in the National Comprehensive Cancer Network. J Clin Oncol. 2008 Nov 1;26(31):5107-12. Epub 2008 Sep 2. PMID: 18768434 

CONCLUSION I..., the majority of common B-cell NHLs diagnosed in the community were unchanged by second opinion review by an expert hematopathologist. However, for one patient in 20, there was a discordance (non-agreement) in diagnosis that could have altered therapy.

See Also Getting A Second Pathology Evaluation

Perspective: "Anecdotal evidence. An oxymoron? Or a valid approach to understanding data? scienceb asedmedicine. org 

Bendamustine: FDA Approval for TREANDA to Treat Patients with Relapsed Indolent NHL marketwatch.com 
 
n= 100 The FDA approval is supported by a pivotal trial of 100 patients with indolent B-cell NHL who had progressed during or within six months of treatment with a regimen that included rituximab. 

Pilot: Feasibility of allogeneic stem cell transplantation for follicular lymphoma undergoing transformation to diffuse large B-cell lymphoma.  Leuk Lymphoma. 2008 Oct;49(10):1893-8. PMID: 18949613 

n = 8 patients with histologically confirmed transformation to diffuse large B-cell lymphoma underwent HSCT at our institution. The median age was 56 years (range 44-63 years).

Allogeneic HSCT appears feasible in patients with transformed FL and is associated with acceptable treatment-related mortality and low relapse rates.

Preclinical: T cell modulation combined with intratumoral CpG cures lymphoma in a mouse model without the need for chemotherapy. Blood. 2008 Oct 21. PMID: 18941113 

n = 0 (preclinical) 

Our results show that the combination of intratumoral CpG and immunomodulatory T cell antibodies has promise for therapeutic vaccination against lymphoma. These reagents are becoming available for human clinical trials.

Review: Hematopoietic SCT for peripheral T-cell lymphoma?
Bone Marrow Transplant. 2008 Oct 20. PMID: 18936735

Study: Lymphoma Patients' Survival Affected By Socioeconomic And Treatment Factors medicalnewstoday.com 

n = >13,000 patients diagnosed at age 65 or older between 1992 and 1999. The metropolitan areas of San Francisco/Oakland, Detroit, Atlanta, Seattle, Los Angeles County, San Jose/Monterey, and the states of Connecticut, Iowa, New Mexico, Utah, and Hawaii were included in this study.

The investigators found that receiving chemotherapy was associated with prolonged survival in patients with NHL and that elderly Caucasian patients with NHL were more likely to receive chemotherapy (52.4 percent) compared with African-Americans (43.2 percent). Also, poor socioeconomic status was significantly associated with increased risk of mortality

Review: Evolving Paradigms in Follicular Lymphoma: Re-Evaluating Prognostic Factors and Challenging Treatment Dogmas molecularonc.com | Cara A. Rosenbaum, MD

Current clinical indices and molecular markers in follicular lymphoma must be re-evaluated and incorporated actively into prospective trials to allow development of risk-adapted treatment guidelines and novel targeted therapies. The results of such studies will help to further recommendations regarding the effective timing of therapeutic intervention (ie, watchful waiting versus active treatment) and the efficacy of various chemotherapeutic regimens in different patient populations.

Initial treatment and risk of transformation: The impact of initial treatment of advanced stage indolent lymphoma on the risk of transformation  ascopubs.org 

n = 698 patients with indolent NHL, no prior treatment, age16–60 y and advanced stage disease (III/ IV or I/ II with B symptoms or bulky disease 10cm). 

"Conclusion: The use of an anthracycline-based regimen as initial treatment for advanced stage indolent NHL is associated with a marked reduction in the risk of future transformation."

T-cell outcome: FDA Grants Full Approval to ONTAK(R) (denileukin diftitox) for Use in Patients with Cutaneous T-Cell Lymphoma (CTCL)  Press release

n = 144 with with refractory CTCL (stages Ia-III), expressing CD25 component of the IL-2 receptor.

Also: FDA approval of ONTAK for this indication NetMedia

Zevalin report: Cell Therapeutics, Still Fighting, Gets Zevalin Data Published In Cancer Journal 

n = 414 patients getting first-line treatment for their slow-growing lymphoma.

Patients on the drug were able to keep their cancer from spreading for a median time of 36.5 months, compared with 13.3 months in a control group. About 77 percent of patients who had partial tumor shrinkage on prior treatments entering the study had their tumors completely wiped out after getting a single shot of Zevalin,

Also see our brochure on when to consider RIT: PDF

Outcomes indolent: Durable complete responses from therapy with combined epratuzumab (anti-CD22) and Rituxan (anti-cd20)  Abstract

n = 41 patients with relapsed/refractory, indolent (NHL

Twenty-two of 41 patients with FL (54%) had an objective response (OR), including 10 (24%) complete responses (CR) (CR/unconfirmed CR [CRu]), whereas 4 of 7 patients with SLL (57%) had ORs, including 3 (43%) with CR/CRu. Rituximab-naive patients (N = 34) had an OR rate of 50% (26% CR/CRu rate), whereas patients who previously responded to rituximab (N = 14) had an OR rate of 64% (29% CR/CRu rate).

Main caveats: Small study, no control, mix of lymphoma types.

Side effects: Full Recovery After Cell Transplantation for Treating Leukemia or Lymphoma Can Take 3-5 Years fhcrc.org 

n = 319 adults who had myeloablative (bone-marrow suppression) HCT for treatment of leukemia or lymphoma, 5-year follow-up.

MCL/indolent outcomes: Phase II multicenter study of bendamustine plus Rituxan in patients with relapsed indolent B-cell and mantle cell NHL.  J Clin Oncol. 2008 Sep 20;26(27):4473-9. Epub 2008 Jul 14. PMID: 18626004  

(n = 66 patients with relapsed, indolent B-cell or mantle cell lymphoma (without documented resistance to prior rituximab)

Overall response rate was 92% (41% complete response, 14% unconfirmed complete response, and 38% partial response). Median duration of response was 21 months (95% CI, 18 to 24 months). Median progression-free survival time was 23 months (95% CI, 20 to 26 months). Outcomes were similar for patients with indolent or mantle cell histologies.

Transformation: Population-Based Analysis of Incidence and Outcome of Transformed NHL. J Clin Oncol. 2008 Oct 6. PMID: 18838711  

(n = 600 patients with newly diagnosed FL) 

CONCLUSION: The annual risk of transformation of FL is 3% continuing without plateau beyond 15 years. Advanced stage at diagnosis is predictive of future transformation. Clinically diagnosed transformation has an equal impact on outcome as biopsy proven transformation.

fNHL Outcomes: Biovest Announces BiovaxID® Anti-Cancer Vaccine Prolongs Cancer-Free 
Survival by 44%   Press release  

(n = 117; 2:1 ratio of BiovaxID versus control)

... that the median duration of complete remission in the BiovaxID arm of the study was 44.2 months which is clinically and statistically significant compared to the control arm, median duration of cancer-free survival of 30.6 months. BiovaxID prolonged the cancer-free survival by 13.6 months or 44% (p-value = 0.045; HR = 1.6) with a median follow up of 56.6 months (range 12.6 to 89.3 months).

Drug approvals: FDA Approvals from July, 2005 to December, 2007 PDF 

Includes indications, endpoints, basis for approvals.

MCL Outcomes: Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo–purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group  bloodjournal.hematologylibrary.org 

(n = 160 consecutive, untreated patients)

Lenalidomide (Revlimid): what is the right dose in CLL?
http://bloodjournal.hematologylibrary.org/cgi/content/full/111/11/5268 

(n = 45 patients with relapsed CLL)

Astonishing progress in treatment of Childhood Hematologic Cancers  http://patient.cancerconsultants.com 

Approximately 40% of childhood cancers are classified as hematalogic cancers. Hematologic cancers are cancers of the blood and bone marrow, and include leukemia and lymphoma. 

For patients to print and bring to next consult: 
Confidential CLINICAL TRIAL SURVEY For Oncologists Treating Lymphoma/CLL Patients PDF 
Purpose: to identify obstacles to enrolling patients in clinical trials.

PAL's POSTER EXHIBIT: Interest, attitudes, and participation in clinical trials

Outcomes LPL / Waldenstrom's: The addition of rituximab to front-line therapy with CHOP (R-CHOP) results in a higher response rate and longer time to treatment failure in patients with lymphoplasmacytic lymphoma: results of a randomized trial of the German Low-Grade Lymphoma Study Group (GLSG).
Leukemia. 2008 Sep 25. PMID: 18818699  

n = 69 patients with previously untreated LPL

Pilot vaccine report: Vaccination with autologous tumor-loaded dendritic cells induces clinical and immunological responses in indolent B cell lymphoma patients with relapsed and measurable disease: a pilot study.  Blood. 2008 Sep 22.  PMID: 18809757 

Collectively these results [single arm study, N= 18] demonstrate that vaccination with tumor-loaded DCs may induce both T and B cell responses and produces clinical benefits in indolent NHL patients with measurable disease.

Basic research: Follicular lymphoma B cells induce the conversion of conventional CD4(+) T cells to T-regulatory cells. Int J Cancer. 2008 Sep 23. PMID: 18814264  

Our study provides evidence for a tumor-specific mechanism by which FL tumor cells promote immune escape through the induction of Treg.

Support: Caregiver burnout: 10 ways to recharge and refocus http://cms.carepages.com/CarePages/en/ArticlesTips/HelpfulTips/better_you.html 

Prognostic marker: Low absolute lymphocyte count is a poor prognostic factor in diffuse-large-B-cell-lymphoma. Leuk Lymphoma. 2008 Sep;49(9):1745-51. PMID: 18798109   

(n = 101 patients with DLBCL who recently completed therapy)

Tests: Positron emission tomography (PET) in mantle cell lymphoma.
Leuk Lymphoma. 2008 Sep;49(9):1693-701. PMID: 18798104  

Outcomes: Intravenous Rituxan® Effective in Primary Central Nervous System Lymphomas  professional.cancerconsultants.com  

(n = 9 patients with PCNSL who had failed other therapies)

...  Rituxan used alone for patients with PCNSL that does not respond to standard therapies may provide effective treatment for some patients, as regression of cancer was achieved in one-third of patients. The authors state that treatment with Rituxan warrants further study in combination with other chemotherapy agents; they add, “Maintenance [Rituxan] is well tolerated and may improve disease control in this patient population.” Further enrollment and follow-up for this trial are ongoing.

Related studies: ClinicalTrials.gov

Outcomes: I-131-based Rituxan  Safe and Effective for Repeat Treatment professional.cancerconsultants.com 

Fourteen of 16 patients responded with nine complete responses (CRs), with a median duration of 10.5 months in responders. Six of 13 reresponders had the same or a longer response and six more remain in complete response. The median event-free survival was not significantly different for the two treatments. There was no significant difference in the severity of myelosuppression. Four patients developed hypothyroidism with three requiring thyroxine. One patient developed AML, with no other cases of MDS. The actuarial progression-free survival rate at 12 months was 36%.  

Comment: encouraging; small study, however; might require longer follow up to assess risks.

Rituxan risk? Late reactivation of resolved hepatitis B virus infection: an increasing complication post rituximab-based regimens treatment? Am J Hematol. 2008 Aug;83(8):673-5. PMID: 18528824 

Drug targets: Differential cellular internalization of anti-CD19 and -CD22 immunotoxins results in different cytotoxic activity. Cancer Res. 2008 Aug 1;68(15):6300-5. PMID: 18676854  

Our results show that the rapid internalization of large amounts of BL22 bound to CD22 makes CD22 a better therapeutic target than CD19 for immunotoxins and probably for other immunoconjugates that act inside cells.  Comment: internalization is when the antibody (and anything bound to it) is taken up into the cell, rather than remaining outside of it. 

NHL/MCL Outcome: Adoptive immunotherapy for indolent NHL and MCL using genetically modified 
autologous [from self] CD20-specific T cells  

Of the 7 treated patients, 2 maintained a previous complete response, 
1 achieved a partial response, and 4 had stable disease. 
These results show the safety, feasibility, and potential antitumor activity of adoptive T-cell therapy using this approach. This trial was registered at Clinicaltrials.gov NCT00012207

Story: Gene Wilder Talks about his lymphoma Utube

Lenalidomide (Revlimid) down-regulates the CD20 antigen and antagonizes direct and antibody-dependent cellular cytotoxicity of rituximab on primary chronic lymphocytic leukemia cells.
Blood. 2008 Sep 4.  http://www.ncbi.nlm.nih.gov/pubmed/18772452 

This is preclinical data, which suggests that Revlimid might work against the activity of Rituxan when treating CLL.  

Review: Aiming at a Curative Strategy for Follicular Lymphoma caonline.amcancersoc.org  
Maurizio Bendandi,MD, PhD   

One clear fact is that no patients will ever be cured by adopting a palliative treatment approach. The assumption that patients with follicular lymphoma are incurable is certain to be a self-fulfilling prophecy. Here the author summarizes the large and growing body of knowledge that suggests an expectant approach to management is not appropriate for all patients. (CA Cancer J Clin 2008;58:305–317.) © American Cancer Society, Inc., 2008.

http://caonline.amcancersoc.org:80/cgi/reprint/58/5/305?eaf  

Outcome: Revlimid (R) Demonstrates Activity against Relapsed/Refractory Aggressive NHL marketwatch.com 

According to the publication, of 49 patients eligible for response evaluation in the study, an objective response was observed in 35 percent, with 12 percent exhibiting a complete or unconfirmed complete response. Activity was also seen in other lymphoma subtypes, including diffuse large b-cell, follicular grade 3 and transformed.  

Outcome: Zevalin® Following an Autologous Transplant?  cancerconsultants.com

"Standard-dose [radioimmunotherapy] seems feasible and potentially effective after [autologous stem cell transplantation] in correctly selected patients with follicular lymphoma."

Report: Adding fresh frozen plasma to Rituxan for the treatment of patients with refractory advanced CLL  oxfordjournals.org  

Five patients with severe treatment-resistant CLL. All had been previously treated with fludarabine and three also failed treatment with Rituxan. ... A rapid and dramatic clinical and laboratory response was achieved in all patients. Lymphocyte counts dropped markedly followed by shrinkage of lymph nodes and spleen and improvement of the anaemia and thrombocytopenia. This could be maintained over 8 months (median) with additional cycles if necessary. Treatment was well tolerated in all cases.

Could CLL be a disease of complement abnormality?
One group reports on this question: ncbi.nlm.nih.gov/pubmed/8751471  

Blood test for fNHL? Serum autotaxin measurement in haematological malignancies: a promising marker for follicular lymphoma. Br J Haematol. 2008 Aug 15. PMID: 18710386 

Report: Zevalin® Effective for Treatment of Cutaneous B-Cell Lymphoma cancerconsultants.com 

100% CR rate in small study (10 patients);
40% (4 of 10 pts) remain in complete remission at 19 months. 

Study: Genmab plans to start ofatumumab studies in CLL & NHL pharmabiz.com

"Ofatumumab is an investigational new generation human monoclonal antibody that targets a distinct, membrane proximal, small loop epitope (specific antibody binding site) of the CD20 molecule on B cells. Ofatumumab is being developed to treat chronic lymphocytic leukaemia, follicular non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, rheumatoid arthritis and relapsing remitting Multiple Sclerosis"

Study: Phase 1,Open Label, Dose-Escalation, Multidose Study in Relapsed/Refractory CLL and Mantle Cell Lymphoma http://clinicaltrials.gov/ct2/show/NCT00730652

MDX-1411 is a fully human monoclonal antibody that targets the CD70 receptor, which is a member of the tumor necrosis factor (TNF) family. CD70 is expressed in a number of cancers, including ccRCC primary tumors and metastatic lesions. lifescience-online.com  

Cellular expression: Activated T and B cells, and macrophages

MDS/ALL: FDA Approves Vidaza  medicalnewstoday.com/

... "AZA-001 trial, which found that Vidaza is the only agent that extends survival in MDS (myelodysplastic syndromes) patients. Vidaza was also shown to delay progression to acute myelogenous leukemia (AML) in patients with MDS. Roughly 30 percent of patients diagnosed with MDS will progress to AML."

"MDS occur when the bone marrow stem cells malfunction [sometimes as a consequence of treatments for lymphomas]. This results in the production of too many defective blood cells and not enough normal cells. Diagnosis is made through blood tests and a bone marrow biopsy. Once diagnosed, treatment and evaluation should occur under the care of a hematologist or hematologist/oncologist. There are many subtypes of MDS classified according to how the disease manifests itself in the blood and marrow of the patient. Treatments include blood transfusions, growth factors, chemotherapy and bone marrow transplant."

BiTE: Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody
Science abstract |  Financial analysis: seekingalpha.com 

Predicting prognosis: Genome-wide profiling of follicular lymphoma by array comparative genomic hybridization reveals prognostically significant DNA copy number imbalances. Blood. 2008 Aug 14. PMID: 18703704  

These prognostic features may be useful to identify high-risk patients as candidates for risk-adapted therapies.

Study of interest: Donor Natural Killer Cell Infusion, Rituximab, Aldesleukin, and Chemo in Treating Patients With Relapsed NHL or CLL 

Background: http://clltopics.org/SponsoredProjects/NKCellTherapy.htm 

Also: Natural killer cell recognition of missing self and haploidentical hematopoietic transplantation.
Semin Cancer Biol. 2006 Oct;16(5):404-11. Epub 2006 Jul 8. Review. PMID: 16916611

"In clinical trials, donor versus recipient NK alloreactions are highly beneficial as they reduce the risk of leukemia relapse, do not cause GvHD and markedly improve event-free survival"

Coffee with Chemo? Common questions and concerns about coffee during cancer treatment 
http://www.cancerboard.ab.ca   

"Coffee acts as a diuretic which increases your urine excretion. During chemotherapy it is important that you keep yourself well hydrated, therefore, it is a good rule of thumb to drink one to two cups (250-500ml) of water for every one cup of coffee you drink."

Study recruiting: Phase I Safety and Pharmacokinetic Study of CT-011, a Humanized Antibody 
Interacting with PD-1, in Patients with Advanced Hematologic Malignancies

http://clincancerres.aacrjournals.org/cgi/content/abstract/14/10/3044 

Biomarkers: Del(6)(q22) and BCL6 Rearrangements in Primary CNS Lymphoma Are Indicators of an Aggressive Clinical Course. J Clin Oncol. 2008 Jul 21. PMID: 18645192  
 
Comment:  Markers such as these, when validated, can be used to tailor therapy to the risk of the disease. 
 
RESULTS: The prevalence of del(6)(q22) and BCL6, IGH, and MYC translocations was 45%,17%, 13%, and 3%, respectively. The presence of del(6)(q22) and/or a BCL6 translocation was associated with inferior overall survival (OS; P = .0097). The presence of either del(6)(q22) alone or a BCL6 translocation alone was also associated with inferior OS (P = .0087).

QOL: 'Futile Care:' What to Do When Your Patient Insists on Chemotherapy That Likely Won’t Help
James Khatcheressian, MD Assistant Professor of Medicine  cancernetwork.com 

MCL outcomes: Long-term progression-free survival of mantle cell lymphoma following intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: A non-randomized phase-II multicenter study by the Nordic Lymphoma Group. Blood. 2008 Jul 14.  PMID: 18625886   

Background: Complementary and alternative medicine in patients with chronic lymphocytic leukemia
Manfred Hensel & Martin Zoz & Anthony D. Ho  springerlink.com pdf  

Conclusion Our data show that patients with CLL use a wide range of CAM, among them potentially harmful methods. Rational, evidence-based medical information about the effects and risks of CAM use should be made available through patient brochures distributed by patient organizations, through information events with lectures, or via the internet.

Alert: Dietary flavonoids inhibit the anti-cancer effects of the proteasome inhibitor Bortezomib (Velcade)

Dietary flavonoids, quercetin and myricetin, which are abundant in plasma, inhibited Bortezomib-induced apoptosis of primary CLL and malignant B-cell lines in a dose-dependent manner. 

Blood First Edition Paper, prepublished online 
July 16, 2008; DOI 10.1182/blood-2008-04-150227.

Sources of flavonoids: http://lpi.oregonstate.edu/infocenter/phytochemicals/flavonoids/

Outcomes:  Biovest Reports Results for Patients Treated with Anti-Cancer Vaccine: BiovaxID(R) Demonstrates Clinically and Statistically Significant Improvement of Disease-Free Survival in Non-Hodgkin's Lymphoma in Pivotal Phase 3 Clinical Trial  http://biz.yahoo.com/

HL Outcomes: High-dose therapy and autologous stem cell transplantation for chemoresistant Hodgkin lymphoma interscience.wiley.com

These data suggest that HDT and ASCT may result in prolonged remissions and survival for a subset of chemoresistant HL patients, with improved outcomes in patients receiving transplants more recently.

Background: Managing and avoiding bortezomib (Velcade) toxicity   communityoncology.net pdf 
Jeffrey Menashe, MD | Northwest Cancer Specialists, Portland, OR

New PAL Topic: What's a Drug?

Outcomes: GM-CSF potentiates Rituxan in relapsed follicular lymphoma (small, single arm study) revolutionhealth.com  | Related studies: ClinicalTrials.gov 

In total, 23 patients (70%) showed an overall response, and there was a "high complete response rate -- 45% -- and prolonged duration of response," Dr. Rossi said. The median progression-free survival was 16.4 months, but it was significantly higher in patients with a complete response (median, 33.2 months) compared with those who had a partial response (median, 7.6 months).

Patterns of mortality after prolonged follow-up of a randomised controlled trial using granulocyte colony-stimulating factor to maintain chemotherapy dose intensity in NHL  

Median follow-up was 15.7 years for surviving patients. No significant differences were found in PFS or OS. However, 10-year FFP was better in the G-CSF arm (68 vs 47%, P=0.037).

Cure for fNHL? Radiolabeled and Native Antibodies and the Prospect of Cure 
of Follicular Lymphoma theoncologist.alphamedpress.org 

"In this review, we hypothesize that the combination of an optimized biological treatment together with radiolabeled antibodies and chemotherapy early in the disease course of advanced-stage follicular lymphoma may represent the best approach to achieve prolonged disease-free survival and eventually cure."

Technical Background: Micromanagement of Lymphomas biology.plosjournals.org/

Lymphomas are tumours composed of lymphocytes. The two types of lymphocytes—T cells and B cells—are distinguished by the antigen receptors on their surfaces and the specific functions they undertake on behalf on the immune system. Precursors of B cells are generated in the bone marrow ...

Alert: 125 Fake Cancer 'Cures' Consumers Should Avoid fda.gov

T-cell Outcomes: Pegylated liposomal doxorubicin effective in poor prognosis CTCL  medwire-news

Of the 10 patients with Sézary syndrome, six (60%) patients achieved an objective response at the end of treatment, including one complete response and five partial responses. Five (50%) of 10 patients with transformed CTCL achieved an objective response, including one patient who achieved a complete response and was still disease-free after 3 years.

FDA Warns Individuals and Firms to Stop Selling Fake Cancer 'Cures'  scienceblogs.com/terrasig/ 

"#1 reason I started this blog was to distinguish therapeutic natural products (i.e., single chemical entities derived from plants, microorganisms, etc.) from questionably-marketed herbal and non-herbal dietary supplements. After doing research and teaching in this area for at least 13 or so years, I have found that patients with cancer and HIV/AIDS are most often preyed upon by unscrupulous marketers."

CTL outcomes: Phase 2 Data for Romidepsin Showing Durable Response in Refractory CTCL businesswire.com 

"Romidepsin is a novel, cyclic peptide, pan-HDAC inhibitor under investigation for hematologic malignancies"

DLBCL: Time of relapse after initial therapy significantly adds to the prognostic value of the IPI-R 
in patients with relapsed DLBCL undergoing autologous stem cell transplantation.
Bone Marrow Transplant. 2008 Apr;41(8):715-20. Epub 2008 Jan 14. PMID: 18195687 

ASCO Research News: 2008 Lymphoma Abstracts  | 2008 CLL/SLL Abstracts

Study of interest:  R-CHOP Versus Dose-Adjusted EPOCH-R 
With Molecular Profiling in Untreated Diffuse Large B-Cell Lymphomas 

Condition: Previously untreated Diffuse Large B-cell Lymphoma 

RATIONALE: It is not yet known which combination chemotherapy regimen is more effective when given with rituximab in treating diffuse large B-cell non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell non-Hodgkin's lymphoma.

Press release: Trial of [novel] BiTE Antibody Blinatumomab (MT103/MEDI-538) in 
Patients with Acute Lymphoblastic Leukemia  earthtimes.org 

""This phase 2 clinical trial in ALL is an important step to assess activity of blinatumomab in aggressive forms of B cell malignancies and will help to determine the full therapeutic potential of this highly specific and potent BiTE antibody in human B cell cancers," said Carsten Reinhardt , M.D., senior vice president and chief medical officer of Micromet."

DLBCL outcomes: Sequential R-CHOP and Zevalin(R) Regimen Produces Impressive Survival Rates in High Risk Elderly Patients With Untreated Aggressive Diffuse Large B-cell Lymphoma  drugs.com  

Senator Grassley speaks out against WSJ Op Ed piece finance. senate.gov  pdf 

"Drug makers and drug developers violate the public interest when they work to muzzle the scientific process and fight disclosure of newly emerging information about various pharmaceuticals in order to drive up their sales and profits. Everyone wants new life-enhancing and life-saving therapies. Cancer patients and others deserve to have information in order to weigh the risks, benefits and unknowns for themselves. "

CLL outcomes: Lenalidomide (Revlimid) induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia

http://bloodjournal.hematologylibrary.org/cgi/reprint/111/11/5291 

Standards: Custodianship and Ownership Issues In Biospecimen Research 

"Biospecimens are critical to the development of new diagnostic, therapeutic, and preventive agents for patients with cancer, yet ensuring equitable and continuous access to these specimens remains a challenge. Individuals charged with the care and keeping of biospecimens often have competing interests regarding who owns the biospecimens, how the biospecimens are used, and who ultimately benefits from them. "

http://biospecimens.cancer.gov/global/pdfs/CaOSumm.pdf  

Notes: You can jump to the section of interest in the above document 
by clicking an item in the table of contents.  PAL was an active participant in this symposium.

Insight: Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets jci.org (full text)

Notably, both phosphorylation of PDGFRα and sensitivity of cultured PTCL cells to imatinib (as well as to an inhibitor of histone deacetylase) were found. These results, which might be extended to other more rare PTCL categories, provide insight into tumor pathogenesis and clinical management of PTCL/U.

Clinical trial:  Gleevec (imatinib) in Relapsed/Refractory T Cell Non-Hodgkin's Lymphoma ClinicalTrials.gov

Great article on Kennedy and Hamilton Jordon:

BETWEEN THE LINES | Jonathan Alter - How We Really Help Ted  newsweek.com
We'll find out if the senators who were crying in the moment will be ready to get serious about cancer. 

About PET: NCCN Task Force Report: PET/CT Imaging (Slides With Transcript)
http://www.medscape.com/viewprogram/8953 

and then click on the first link.
http://www.medscape.com/viewarticle/571872 

Nancy writes: There is a very cool page on reading PET scans. It seems like it is meant for teaching radiology students. It shows differences in PET scans of the same person before and after she ate a bagel with cream cheese, a person who is breast feeding, a person who has had hiccups. It's very interesting to actually see what we talk about so much here. The occurrence of PET activity for reasons other than lymphoma (or other cancer). I highly recommend this site if you've never seen PET results. Mozart's Mom from the Hodge side found it. You can't get there directly from a link without signing up to the site but if you search through Yahoo you can access it. 

Disappointing news: Favrille pulls plug on lead drug candidate (FavId) Marketwatch 

Resource: Daily Meds database http://dailymed.nlm.nih.gov/dailymed/about.cfm 

DailyMed provides high quality information about marketed drugs. This information includes FDA approved labels (package inserts). This Web site provides health information providers and the public with a standard, comprehensive, up-to-date, look-up and download resource of medication content and labeling as found in medication package inserts.

Randomized study: cladribine alone or in combination with cyclophosphamide, and cyclophosphamide, vincristine and prednisone in previously untreated low-grade B-cell non-Hodgkin lymphoma patients: final report of the Polish Lymphoma Research Group. Cancer. 2008 May 9. PMID: 18470902  

Basic research: Natural killer cells: diversity in search of a niche: 
http://www.nature.com/ni/journal/v9/n5/pdf/ni.f.201.pdf  

May 15: Senate HELP Committee Examines Cancer Challenges and Opportunities, 
House Passes Genetic Information Nondiscrimination Act, 
FDA Changes Acceptance Criteria for Foreign Clinical Trials ASCO

UK: Zevalin Licensed For First Line Consolidation Therapy for fNH, May 2008L medicalnewstoday.com

"It is particularly impressive that with one single infusion of Zevalin, we have achieved prolongation of median progression free survival by two years, with a favorable toxicity profile," said Professor Anton Hagenbeek, Academic Medical Centre, Amsterdam, the Netherlands, lead investigator of the FIT trial.

Blood markers that may predict outcomes: Correlation of serum IL-6, IL-8 and IL-10 levels with clinicopathological features and prognosis in patients with diffuse large B-cell lymphoma.  
Int J Lab Hematol. 2008 Jun;30(3):230-9. PMID: 18479302  

...  analysis identified elevated values of IL-6 and IL-10 and response to therapy as significant predictors for overall survival. Serum levels of IL-6, IL-8 and IL-10 before treatment of patients with newly diagnosed DLBCL may give some insight into the possible prognosis and thus facilitate the decisions regarding therapeutic approaches for individual patients.

Review: Renaming "chemobrain". Cancer Invest. 2007 Sep;25(6):373-7. Review. PMID: 17882646

For some, a fear of this side effect enters into their decision regarding therapy. Our review of the literature reveals that so-called "chemobrain" is complex and that factors other than chemotherapy may affect cognitive function, including the impact of surgery and anesthesia, hormonal therapy, menopause, anxiety, depression, fatigue, supportive care medications, genetic predisposition, comorbid medical conditions, or possibly paraneoplastic phenomenon. Studies to date have differed in their assessment and definition of cognitive impairment, thus, making comparisons between studies difficult.

We propose that the phenomenon commonly referred to as "chemobrain" would be more accurately labeled "cancer- or cancer-therapy-associated cognitive change."

min-SCT for HL: Superiority of reduced-intensity allogeneic transplantation over conventional treatment for relapse of Hodgkin's lymphoma following  autologous stem cell transplantation

This study compares outcome of reduced-intensity conditioned transplant (RIT) with outcome of conventional non-transplant therapy in patients with Hodgkin's lymphoma relapsing following autograft.

There were 72 patients in two groups who had relapsed, and received salvage therapy with chemotherapy radiotherapy. 

One group (n=38) then underwent alemtuzumab-containing RIT. The second group-historical controls (n=34), relapsing before the advent of RIT-had no further high-dose therapy.

This group was required to respond to salvage therapy and live for over 12 months post-relapse, demonstrating potential eligibility for RIT, had this been available.

Overall survival (OS) from diagnosis was superior following RIT
   (48% at 10 years versus 15% ; P=0.0014),

as was survival from autograft
   (65% at 5 years versus 15% ; P0.0001).

For the RIT group, OS at 5 years from allograft was 51% , and in chemoresponsive patients was 58% , with current progression-free survival of 42% .

Responses were seen in 8 of 15 patients receiving donor lymphocyte infusions (DLI) for relapse/progression, with durable remission in five patients at median follow-up from DLI of 45 months (28-55).

These data demonstrate the potential efficacy of RIT in heavily pre-treated patients whose outlook with conventional therapy is dismal, and provide evidence of a clinically relevant graft-versus-lymphoma effect.

full text: http://www.nature.com/bmt/journal/v41/n9/full/1705977a.html 

Clinical outcome: StemEx to expand cord blood-derived stem cells

Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraethylenepentamine: a phase I/II clinical trial  nature.com/bmt

One limitation of cord blood-derived stem cells is insufficient quantity of  stem cells from this source. This clinical study applied a new technology  (use of StemEx to expand the number of stem cells (cd34+)) with the goal of  making SCT feasible for people without a matched donor. 

Elderly: A phase II study of liposomal daunorubicin, in combination with cyclophosphamide, vincristine and prednisolone, in elderly patients with previously untreated aggressive non-Hodgkin lymphoma.
Leuk Lymphoma. 2008 May;49(5):924-31. PMID: 18464112  

The response rate to COP-X was similar to that expected with CHOP, with low cardiac toxicity. The high rate of infectious complications suggests that the DaunoXome dose used may be too high for this patient group. These results support further investigation of this regimen in patients with aggressive NHL.

Outcomes: R-CHOP-14 in patients with DLBCL younger than 70 years: a multicentre, prospective study.  Abstract

After therapy, 58 patients (73%) achieved CR-CRu (95% CI: 55-90%). With a median follow-up of 26 months, progression-free survival (PFS) and overall survival (OS) at 30 months were 72% and 86%, respectively. Administration of R-CHOP-14 is feasible and effective in patients <70 years.

Review: Gemcitabine in the treatment of Hodgkin lymphoma - Abstract 2008

Big news: Paraffin-based 6-gene model predicts outcome in diffuse large B-cell lymphoma patients treated with R-CHOP. Blood. 2008 Apr 29. PMID: 18445689 

These findings demonstrate that the prognostic value of the 6-gene model remains significant in the era of R-CHOP treatment and that the model can be applied to routine FFPE (-fixed paraffin-embedded) tissue from initial diagnostic biopsies.

Statins for patients with lymphoma? 

Alert: Medicare 5-year cancer bill tops $21.1 bln: study reuters.com

"There were about 10 million Americans living with cancer in 2003. The National Cancer Institute has estimated that, overall, the United States spent $72.1 billion in 2004 in direct costs for cancer care."

Fatigue: Physical Exercise May Help Reduce Fatigue During and After Cancer Treatment Medscape

"Exercise appears to have some benefit in the management of fatigue both during and after cancer treatment," the reviewers conclude. "Therefore it should be considered as one component of the management strategy for fatigue that may include a range of other interventions and education. . . . Further work is necessary to determine the most effective parameters of exercise for fatigue management including the types of exercise (aerobic and resistance), mode of exercise, frequency and length of sessions, and intensity of exercise carried out."

Encouragement:  A message for the newly diagnosed PAL

HL trends: Ongoing improvement in long-term survival of patients with Hodgkin disease at all ages and recent catch-up of older patients. Blood. 2008 Mar 15;111(6):2977-83. Epub 2007 Dec 20.  PMID: 18096762  

Our period analysis discloses ongoing, major improvement in long-term survival of patients with HD in recent years, particularly among older patients.

Open Letter to SEER:  Regarding capturing statistics for lymphoma subtypes PAL seerltr.pdf 

The SEER website has improved, but the utility of the statistics for non-Hodgkin's lymphomas continue to suffer because subtypes of the disease are not yet provided. 

Make your views known to SEER:  http://seer.cancer.gov/about/contact.html 

Hoax email (Johns Hopkins) about cancer treatment and causes cancerhelp.org.uk 

I've been sent an email, which is really worrying me. I have cancer and this says my treatment won't help and may even harm me. It's also made me worry that heating foods in the microwave for my kids will give them  cancer - it says this information comes from an American University called  Johns Hopkins. Can you tell me if any of this is true?

Secondary cancers: Risk Of Second Cancers Greatest In Younger Patients Treated For Non-Hodgkins Lymphoma medicalnewstoday.com 

"The fact that tumour toll is largest 21 to 30 years after diagnosis has important implications for the timing of medical surveillance schemes for patients with NHL. "Longer follow-up periods of patients will be needed to fully characterize the long-term effects of NHL therapy," they write, adding the individual solid tumours are likely to show variable responses."

Preclinical: Blocking NK cell inhibitory self-recognition promotes antibody-dependent cellular cytotoxicity in a model of anti-lymphoma therapy. J Immunol. 2008 May 1;180(9):6392-401.  PMID: 18424763 

The results show, for the first time, that disruption of inhibitory self-recognition can efficiently promote ADCC in a human model, applying an autologous system in which physiologic checkpoints are in place. This method provides an alternative approach to potentiate the therapeutic benefit of antitumor Abs that mediate ADCC.

Risk factors: Non-Hodgkin lymphoma risk increased by some autoimmune disorders  medscape.com 

The risk of NHL was increased 6.5-fold in patients with Sjgren syndrome, 2.7-fold in patients with systemic lupus, and 2.6-fold in patients with hemolytic anemia, the authors report

Risk factors: Plasma donation associated with risk for non-Hodgkin's lymphoma hemonctoday.com 

Frequent plasma donors appeared to have a higher risk for non-Hodgkin's lymphoma (>25 vs. 0 donations, OR 2.14). The researchers concluded that this finding warrants additional examination. – by Stacey L. Adams   Natl Cancer Inst.2008;100:1-8.

fNHL outcomes: 8-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide and rituximab.
Blood. 2008 Apr 14; PMID: 18411419 

Forty-seven patients were included. All patients experienced complete remission, with only 2 relapses. With a median follow-up time of 60 months (range, 19-94), the estimated survival and progression-free survival rates were 85% and 83%, respectively.

CNS outcomes: Intensive Chemotherapy Followed by Hematopoietic Stem-Cell Rescue for Refractory and Recurrent Primary CNS and Intraocular Lymphoma: Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. J Clin Oncol. 2008 Apr 14; PMID: 18413641  

The respective median progression-free survival (PFS) times after IC + HCR were 11.6 and 41.1 months. The 2-year overall survival probability was 45% in the whole population and 69% among the 27 patients who received IC + HCR. The 2-year PFS probability was 43% among all the patients and 58% in the IC + HCR subpopulation. CONCLUSION: IC + HCR is an effective treatment for refractory and recurrent PCNSL.

Technical background: Bone-marrow haematopoietic-stem-cell niches, Anne Wilson and Andreas Trumpp  nature.com   PDF 

fNHL outcomes:  Dr. Ronald Levy, LB-204: Results of a Phase III trial evaluating safety and efficacy of idiotype vaccine, compared to non-specific immunotherapy.   AACR Webcast

fNHL outcomes: Preliminary results of a Phase I study of AME-133v, an Fc-engineered humanized monoclonal antibody, in low-affinity Fc?RIIIa patients with previously-treated follicular lymphoma: LB-70 

http://www.acor.org/news/display.html?id=6643 (scroll down to article) 

AME-133v is a second-generation therapy that is believed to be a more specific treatment for follicular lymphoma in general, compared to rituximab, but is also thought to offer particular benefits for those patients who have a variant in the immune cells needed to attack the cancer, Forero says.

Preclinical Non-invasive Targeted Radiofrequency  Cancer Treatment  Destroying Cancer Cells with Radio Waves  kanziuscancerresearch.com/  

"The treatment concept: ... a “targeting molecule” (antibody) is designed that will seek out and attach to or penetrate through that unique site, the targeting molecule is chemically attached to a gold nanoparticle or carbon nanotube, and the combination is injected into the bloodstream of the patient. The targeting molecule(s) eventually delivers the nanoparticle(s) to the cancer cell(s). It is particularly exciting that metastatic cancer cells might also be targeted. Exposure of the area to the radiowaves causes the nanoparticles to warm sufficiently to kill the cancer cells. This will require an extensive research effort, especially to be able to ultimately treat the variety of cancers potentially susceptible to this treatment approach." 

New cd20 Mab: First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase I/II trial.
Blood. 2008 Apr 4; PMID: 18390837 | Related articles 

Clinical response rates ranged from 20-63%. Median time to progression (TTP) for all patients/responders were 8.8/32.6 months and median duration of response was 29.9 months at a median/maximum follow-up of 9.2/38.6 months. Ofatumumab is currently being evaluated in patients with rituximab-refractory FL. This trial was registered at www.clinicaltrials.gov NCT00092274.

Clinical trials: White Paper on the Shortcomings of How Clinical Trials are Designed, Carried Out and Funded in the U.S. EDICT 

But while the need for clinical research is undisputed, how clinical trials are now conducted remains problematic. Increasing research finds major deficiencies in the way clinical trials are designed, carried out and funded in the U.S. with serious implications for the outcomes of medical research studies. 

Life style: Smoking, drinking imperil lymphoma survival reuters.com  

The results should strongly encourage patients with NHL "to stop smoking and lower alcohol consumption in order to obtain a general health benefit and improvements in the course of treatment," Talamini advised. 

Case report: Cutaneous follicular center B-cell lymphoma treated with intralesional rituximab.
Actas Dermosifiliogr. 2008 May;99(4):291-6. Spanish.  PMID: 18394405 | Related articles

We also review the published cases of cutaneous B-cell lymphoma treated with intralesional rituximab.

Outcomes: Summary of MyVax Personalized Immunotherapy Phase 3 Clinical Trial Results media.corporate-ir.net   pdf  

"Genitope believes that the failure of its MyVax Phase 3 clinical trial to meet its primary endpoint was due to unrecognized activity in the non-specific immunotherapy."

QOL: Long-Term and Late Effects of Treatment in Adults leukemia-lymphoma.org    pdf 
No. 22 in a series providing the latest information for patients, caregivers and healthcare professionals

Identify patients with high-risk fNHL: Predicting outcome in follicular lymphoma by using interactive gene pairs. Clin Cancer Res. 2008 Jan 15;14(2):478-87.  PMID: 18223222  

The evidence reported here may provide the basis for an expression-based, multi-gene test for predicting poor follicular lymphoma outcomes.

Assessing response to treatment early: Diffusion MRI shown to give early signs of cancer's response to treatment cancer.med.umich.edu

 In the first study of its kind, researchers from the University of Michigan Comprehensive Cancer Center are reporting success in analyzing diffusion MRI images to distinguish between dead and living brain tumor cells in both animals and humans. They report that the imaging technique, which tracks the movement of water through and between cells, allowed them to assess the effect of therapy on the cancer without relying on measurable changes in tumor size.

Clinical Trial: Pilot Study of Diffusion MRI as a Tool for Early Evaluation of Tumor Response in Diffuse Large B Cell Lymphoma (dMRI)  http://clinicaltrials.gov/ct2/show/NCT00645359 

HL risk factor: USC researchers find new clues to risk of Hodgkin lymphoma genengnews.com 

A long-term study of twins has led University of Southern California (USC) researchers to find potential links between Hodgkin lymphoma and levels of an immune response protein (interleukin-12).

Preventing / managing oral mucositis (resources) - common and serious side effect related to high dose therapy and stem cell transplantation  Abstract

Review: Lenalidomide for the treatment of B-cell malignancies. 
J Clin Oncol. 2008 Mar 20;26(9):1544-52. Epub 2008 Feb 19. Review.  PMID: 18285605 

"Its antitumor activity seems mediated through modulation of both the cytokine and cellular tumor cell microenvironment. Preclinical as well as clinical observations demonstrate that lenalidomide downregulates production of various critical prosurvival cytokines in the tumor microenvironment while concurrently promoting activation of T- and natural killer (NK) cell-mediated antitumor response. ...  Consequently, the role of lenalidomide in other B-cell malignancies has been investigated, with impressive results in chronic lymphocytic leukemia and non-Hodgkin's lymphoma. This review summarizes the data from various clinical investigations and highlights the impact of lenalidomide in the management of patients with B-cell malignancies."

Perspective: How Quackery Harms Cancer Patients quackwatch.com 

There is an old saying: "The highwayman demands 'your money OR your life,' but quacks demand 'your money AND your life!'" This statement is particularly true when it comes to dubious cancer treatment. The harm done by quackery may be categorized as economic, direct, indirect, psychological and societal.

RIT usage: CHMP Recommends Positive Opinion For Zevalin, In First Line Consolidation Therapy For Follicular Lymphoma  http://www.medicalnewstoday.com/articles/101670.php  

The recommendation is based on data from the First-line Indolent Trial (FIT) study. The FIT study shows nearly a 2 year improvement in progression free survival (PFS) in patients with advanced follicular lymphoma receiving [90Y]-ibritumomab tiuxetan vs, induction chemotherapy alone.1

Alert:  Statins [commonly prescribed drug] Impair Antitumor Effects of Rituxan by Inducing Conformational Changes of CD20  medicine.plosjournals.org/  

Statins were shown to interfere with both detection of CD20 and antilymphoma activity of rituximab. These studies have significant clinical implications, as impaired binding of mAbs to conformational epitopes of CD20 elicited by statins could delay diagnosis, postpone effective treatment, or impair anti-lymphoma activity of rituximab.

Big news: Treanda (Bendamustine) approved for chronic lymphocytic leukemia - http://health.usnews.com/usnews/health/healthday/080320/treanda-treats-rare-cancer.htm  

New: Treanda (Bendamustine) Full Prescribing information: FDA as PDF file

Sad news: Page Irby's personal fight with lymphoma ended on March 11, 2008, but not her legacy 

Page was and will remain an inspiration to me in her approach to life. As you may know, she was committed to helping others to navigate the medical system and was an articulate advocate for becoming an informed and proactive patient. 

Case report on safety: Lethal vascular leak syndrome after denileukin diftitox administration to a patient with cutaneous gamma/delta T-cell lymphoma and occult cirrhosis. Am J Hematol. 2008 Feb 15; PMID: 18335564

Bad news: Genitope halts MyVax work, examines future bizjournals.com 

... said it will suspend work on its cornerstone personalized cancer vaccine, MyVax, for follicular non-Hodgkin's lymphoma.

Also see our commentary

Allo versus Auto SCT: Outcome of BEAM-autologous and BEAM-alemtuzumab allogeneic transplantation in relapsed advanced stage follicular lymphoma. Br J Haematol. 2008 Mar 3 PMID: 18318762  | Related articles 

CNS outcomes: Primary central nervous system lymphoma: mono-center, long-term, intent-to-treat analysis.
Cancer. 2008 Mar 4; PMID: 18318432  | Related articles

Promising long-term results could be achieved with HDMTX-based chemotherapy in patients with PCNSL in this monocenter study. The MSKCC score proved useful for predicting survival.

MRI imaging: Magnetic resonance imaging for the detection of bone marrow involvement in malignant lymphoma. Br J Haematol. 2008 Apr;141(1):60-8.  PMID: 18324967 

MRI is probably sufficiently sensitive to rule out bone marrow involvement in patients with malignant lymphoma. However, a well-designed study with a large sample size is needed to confirm current results.

New study of interest: Fenretinide and Rituxan

Secondary treatment risks: Liver dysfunction after chemotherapy in lymphoma patients infected with hepatitis C blackwell-synergy.com 

... "baseline screening for HBV and HCV before initiation of chemotherapy is crucial. High-risk patients having chronic active hepatitis, high baseline HCV viral load, HBV co-infection and receiving cytotoxic drugs, corticosteroids and rituximab (particularly if combined) should be closely monitored for serum transaminase, bilirubin and HCV RNA levels."  

Drug development: Traditional Medicine: Identifying Potential Cancer Treatments Of Herbal Origin http://www.sciencedaily.com 

ScienceDaily (Mar. 5, 2008) — Curing cancer with natural products -- a case for shamans and herbalists? Not at all, for many chemotherapies to fight cancer applied in modern medicine are natural products or were developed on the basis of natural substances. Thus, taxanes used in prostate and breast cancer treatment are made from yew trees.  The popular periwinkle plant, which grows along the ground of many front yards, is the source of vinca alkaloids that are effective, for example, against malignant lymphomas. 
The modern anti-cancer drugs topotecan and irinotecan are derived from a constituent of the Chinese Happy Tree.

DLBCL Outcomes: CHOP-Zevalin(R) Investigational Regimen Produces 95% Complete Remission and 75% Estimated Two Year Progression-Free Survival in Elderly Patients with Diffuse Large B-cell Lymphoma  prnewswire.com: 

In this study, 20 previously untreated elderly patients were treated with a novel combination of six cycles of CHOP chemotherapy followed by Zevalin given six to ten weeks later. 

MCL outcomes report: Low-dose metronomic, multidrug therapy with the PEP-C oral combination chemotherapy regimen for mantle cell lymphoma. Leuk Lymphoma. 2008 Mar;49(3):447-50.  PMID: 18297520  

Eighty-two percent achieved an objective response with 46% complete responses and 36% partial responses. Median time on therapy was 17 months. The regimen was well tolerated. Our findings demonstrate that low-dose oral agents administered in combination for continuous, prolonged periods with minimal drug-free intervals (metronomic therapy) may represent a novel, effective, easily tolerated approach to MCL and that this treatment approach warrants further exploration.

Association: Prognostic influence of tumor-infiltrating mast cells in follicular lymphoma patients treated with rituximab and CHOP. Blood. 2008 Feb 28; PMID: 18309035 

...  the data demonstrate that high MC (tumor-associated mast cells) score is associated with unfavorable prognosis and it eliminates the positive prognostic value of TAMs (tumor associated macrophage) in FL patients treated with immunochemotherapy.

Early Prognostic: C-MYC translocation in t(14;18) positive follicular lymphoma at presentation: An adverse prognostic indicator? Leuk Lymphoma. 2008 Mar;49(3):470-6. PMID: 18297523

This is a small series but one which raises the possibility that the presence of a C-MYC translocations at presentation may identify a particularly aggressive subtype of FL. Further studies are required to investigate the true incidence of this aberration, the impact on C-MYC regulation, clinical course and response to treatment.

Newsy report: low dose Radiotherapy + CpG immunotherapy: smh.com.au 

Professor Ronald Levy, acclaimed cancer researcher and head of the Division of Oncology at Stanford University, said the radiotherapy killed cancer cells at the injection site, but the stimulant triggered the immune system to track and exterminate deadly cells elsewhere in the body. 

"Of the 13 patients in the pilot study, four are in remission," Prof Levy said.

Quality of life: Expressive Writing Appears To Change Thoughts And Feelings About Cancer http://www.medicalnewstoday.com:80/articles/98355.php  

49 percent of participants who completed the writing exercise reported that writing changed their thoughts about their illness, while 35 percent reported writing changed they way they felt about their illness. At the three week follow-up, 54 percent of those completing all parts of the study reported writing changed their thoughts and 38 percent reported writing changed their feelings about their illness. Two factors -- younger age, and less time since diagnosis, were associated with more change in thoughts and feelings.

Future target for therapy? B Cell Mutations That May Cause Cancers And 
Autoimmune Diseases medicalnewstoday.com/ 

Dr Brink believes his team has uncovered an important clue as to how these diseases may be treated in the future. "When we examined the genes expressed in the long-lived B cells, we noticed that mutations in the TRAF2 or TRAF3 gene cause major changes to other genes within the B cell. We found around 20 genes whose expression went up dramatically in these cells.

Preclinical immunotherapy:  Novel Way To Develop Tumor Vaccines: Regulate Immune Inhibitor To 
Overcome Tumor Suppression sciencedaily.com/

The study identified a new molecular player called A20, an enzyme that restricts inflammatory signal transduction in dendritic cells. When it is inhibited, the dendritic cells overproduce an array of cytokines and co-stimulatory molecules that triggers unusually strong immune responses that cannot be suppressed by regulatory T cells. The resulting hyperactivated immune responses triggered by A20-deficient dendritic cells are capable of destroying various types of tumors that are resistant to current tumor vaccines in mice.

Clinical trial participation: Most Cancer Patients Satisfied With Clinical Trial Experience,
 Yet Few Aware of Opportunity  foxcentraloregon.com/ 

The survey determined that only 10 percent of the 1,788 cancer survivors knew participation in a cancer clinical trial was an option. Of those who learned about trials, 73 percent cited their physician as the source of information. The participants' type of cancer influenced their awareness, as did type of treatment.

"One of the most important steps a patient can take to regain some control when faced with a cancer diagnosis is to be as informed as possible about his or her disease," said Dr. Miller. "It was encouraging to find that most patients would be inclined to participate if enrollment in a clinical trial was presented as a treatment option."

Infection-driven? Eliminating Infection at Diagnosis of Slow-growing NHL May Be Important Treatment Step  cancerconsultants.com:

It appears that indolent NHL in patients with an infection may have a different biology from indolent NHL in patients without an infection, as evidenced by the differences in time required for NHL therapy. As well, it appears that antimicrobial therapy may provide benefit for some patients with indolent NHL and an infection. Although this topic needs further study, these results provide provocative data that may lead to different treatment strategies in NHL.

Dubious promotions:  Low dose Naltrexone and Cancer?

The Big picture:  Battling the Hematological Malignancies: The 200 Years' War

Full article  http://theoncologist.alphamedpress.org/cgi/content/full/13/2/126 

The delineation of the hematological malignancies began near the end of the first third of the 19th century ...  These challenges will be gradually overcome, if we (a) develop new models of cooperation among academia, industry, and government [and patients], (b) continue the growth of international participation in cancer research (more keen minds to the task), and (c) convince the governments of the world, including that of the U.S., that an investment in minimizing the effects of cancer is as important as defending against other threats to the welfare and longevity of their citizens.

Education: Spotlight on New Discoveries in NHL: leukemia-lymphoma.org 
Update from the American Society of Hematoloty (ASH) Annual Meeting

This program featured Wyndham Wilson, M.D., Ph.D, senior investigator, head, Lymphoma Therapeutics Section, National Cancer Institute, Bethesda, MD. 

Updated Clinical Practice Guidelines for Oncologists: nccn.org   pdf 2008

Technical guidance for treatments of lymphomas by type.

Updated: Tools and Tips for Patients

Review: Zevalin in Mantle Cell Lymphoma touchbriefings.com   pdf  2007

Conclusion: Radiotherapy is an active treatment modality in MCL. Ibritumomab radioimmunotherapy (Zevalin) is an interesting alternative to other consolidation methods. In younger patients subjected to intensive chemotherapy followed by autologous transplant, it may be an element of a transplant conditioning regimen (i.e. Z-BEAM). In elderly patients, the role of zevalin consolidation should be further investigated in a phase III trial.

CLL Outcomes: Phase I-II study of oxaliplatin, fludarabine, cytarabine, and rituximab combination therapy 
in patients with Richter's syndrome or fludarabine-refractory CLL. 
J Clin Oncol. 2008 Jan 10;26(2):196-203. PMID: 18182662  

The OFAR regimen is highly active in RS and has activity in fludarabine-refractory patients with CLL. This regimen warrants further investigation in the treatment of these disorders.

Risk factors for development of a second lymphoid malignancy in patients with CLL. 
Br J Haematol. 2007 Nov;139(3):398-404. PMID: 17910629

Preclinical: AT-101 markedly enhances the therapeutic effects of chemotherapeutic agents in in vitro and in vivo models of B-cell lymphoma. Blood. 2008 Feb 21; PMID: 18292288  

Over-expression of anti-apoptotic members of the Bcl-2 family are observed in approximately 80% of B-cell lymphomas, contributing to intrinsic and acquired drug resistance. Nullifying anti-apoptotic function can potentially overcome this intrinsic and acquired drug resistance. ... The addition of AT-101 to cyclophosphamide (Cy) and rituximab (R) in a schedule-dependent manner enhanced the efficacy of the conventional therapy [ in cell culture and animal models].

Clinical trials with AT-101

AITL Prognostic factors: Clinical, biological and pathological features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials. Blood. 2008 Feb 21; PMID: 18292286  

"In multivariate analysis, only male gender (p=0.004), mediastinal lymphadenopathy (p=0.041) and anemia (p=0.042) adversely affected overall survival. 

... In conclusion, AITL is a morphologically heterogeneous T-cell lymphoma commonly expressing CXCL13 and CD10 and carrying few prognostic factors. It portends a poor prognosis even when treated intensively. However, not always lethal as 30% of patients are alive at 7 years."

Quality of life: Post-traumatic stress (PTS) outcomes in NHL survivors. ncbi.nlm.nih.gov 

Treanda FDA review starts: FDA Accepts Treanda New Drug Application for the Treatment of Relapsed Indolent NHL drugs.com

We are pleased that the application for Treanda to treat relapsed indolent NHL is on track. With two NDAs for Treanda pending review decisions, 2008 is a significant year for this product ...

Insight: Into Possible Cause of Lymphoma medicalnewstoday.com 

What this means, Schatz said, is that researchers studying lymphatic cancer must understand both the first and the second step-the original mutations and then the repair process.

CLL news: MabCampath Available For First Line Treatment Of B-Cell Chronic Lymphocytic Leukaemia (CLL) For Whom Fludarabine Chemotherapy Is Not Appropriate  medicalnewstoday.com/articles/97739.php 

"In the Phase III trial MabCampath® produced the highest response rate in patients with chronic lymphocytic leukaemia for any single agent seen in previous front-line trials," said Dr Peter Hillmen of the department of clinical haematology and haematological malignancy diagnostic service at Leeds teaching Hospital and principal trial investigator for MabCampath®.

Caution on high dose green teas supplements: 
Green tea can be toxic at therapeutic dose levels pubs.acs.org  pdf 

"Despite several human studies that showed no toxicity of tea polyphenol preparations and that the major adverse effects associated with consumption of high doses of tea preparations are due to gastrointestinal irritation, there have been a number of recent case reports of hepatotoxicity related to the consumption of high doses of tea-based dietary supplements (10-29 mg/ kg/day po) (18)."

Quality of Life: Optimism Not Required for Cancer Recovery  healthtalk.com  

Contrary to popular belief, there is no evidence that an optimistic attitude leads to a better cancer outcome. In fact, insisting on a cheery disposition when someone is struggling with a scary disease may actually do more harm than good, according to a leading psycho-oncologist (a psychiatrist specializing in the treatment of cancer patients).

Weighing the evidence: The Dirt on Coming Clean: Perverse Effects of Disclosing Conflicts of Interest 
Daylian M. Cain, George Loewenstein, and Don A. Moore http://www.cbdr.cmu.edu/mpapers/CainLoewensteinMoore2005.pdf 

Notable quote: " While most people think conflicts of interest are a problem of overt corruption, that is, that professionals consciously and intentionally misrepresent the advice they give so as to secure personal
gain, considerable research suggests that bias is more frequently the result of motivational processes that are unintentional and unconscious "

Advocacy works! Congress Grants Reprieve for Cancer Treatment (RIT) heartland.org  

... Like chemotherapy, radioimmunotherapy drugs treat and kill cancer cells, but they use radioactive material to do so. Bianco said Congress responded to the *vast patient and physician outcry* against CMS's decision.

Sources of information Webpages that contain information about CAM  interscience.wiley.com 

Most breast cancer information that consumers are likely to encounter online is accurate. However, commonly cited quality criteria do not identify inaccurate information. Webpages that contain information about CAM (Complementary and Alternative Medicine) are relatively likely to contain inaccurate statements. Consumers searching for health information online should still consult a clinician before taking action.

Early/encouraging: BiTE Antibodies (report on clinical responses) seekingalpha.com 

A BiTE (Bispecific T Cell Engager) antibody is a bi-specific antibody (bsAb) which directs T-cells to attack cancer cells, by simultaneously binding the two cells. 

... all three patients who received the highest dose, had an objective response ( One had a CR and the other two had PRs). It won’t be reasonable to expect that this dose can actually achieve 100% response rate in larger populations, but this is indeed a great sign of a dose dependent activity. 

While the response rate of this trial is very encouraging, the actual doses which led to the responses are nothing short of sensational. MT103 was effective at doses at which most antibody-based platforms are not even evaluated.

Presidential candidates statements on healthcare: 

Clinton | Huckabee | McCain | Obama | Romney

Early encouraging: Novel Anti-CD20 Monoclonal Antibody Ofatumumab Demonstrates Anti-tumour Responses In Patients With Relapsed/refractory B-cell Chronic Leukaemia  medicalnewstoday.com

... four weeks after beginning treatment, 62% of patients (N=32) obtained objective response

HL Prognosis: Better Prognosis for Patients with Lymphocyte-predominant Hodgkin’s Lymphoma patient.cancerconsultants.com 

"In order to better understand characteristics of LPHL [Lymphocyte-predominant HL], researchers from Germany conducted an analysis of 8,298 HL patients treated within a German medical trial to compare patient characteristics and treatment outcomes among cHL [classical HL) patients and others diagnosed with LPHD . "

fNHL Outcomes: Comparing intensive (R-HDS - with autografting) versus CHOP-R in high-risk follicular lymphoma at diagnosis.  Blood. 2008 Jan 31; PMID: 18239086 

the superior disease control of R-HDS does not translate into an over-all survival advantage.

Background for patients: Factors that can influence treatment decisions and timing: PAL 

The purpose of this "inventory" of factors is to show the complexity of treatment decisions - and how they can interact; and how each case and lymphoma can be unique, thus treatments may need to be tailored accordingly.

HL: Prognostic impact of bone involvement in Hodgkin lymphoma.
Neoplasma. 2008;55(2):96-100. PMID: 18237246 

...  bone involvement is a relatively common finding in HL and is not an independent adverse prognostic factor. Key words: Hodgkin lymphoma - bone involvement - prognostic factors.

Expert perspective: Follicular Lymphoma Revisited, Saul A. Rosenberg  jco.ascopubs.org 

In conclusion, reflecting on our report of transformation of follicular lymphoma, of 25 years ago, and the 50 years’ experience of the author, this event remains a most important one in the course and life of a patient with follicular lymphoma, but so is the attitude, skill, and judgment of the physician managing these special patients.

Health: Final Rule Promotes Safe Use of Dietary Supplements fda.gov 

Under the final rule, manufacturers are required to evaluate the identity, purity, quality, strength, and composition of dietary supplements.

Outcomes CNS Lymphoma : Methotrexate May Cure up to 20% of Patients With CNS lymphoma medscape (free login req.)

"In this small, multicenter study we found that at almost 7 years of follow-up, 5 of the original 25 patients were still in remission after treatment with high-dose methotrexate alone and that toxicity was modest," principal investigator Tracy Batchelor, MD, told Medscape Neurology & Neurosurgery. 

The study is published in the January 29 issue of Neurology.

Review of ASH: Report from the 49th Annual Meeting 8–11 December, 2007, Atlanta, Georgia  
David Meiklejohn, Consultant Haematologist, Ninewells Hospital, Dundee, UK lymphomaforum.org.uk

* Does upfront treatment of diffuse large B-cell lymphoma (DLBCL) with rituximab and chemotherapy (R-chemotherapy) make relapsed disease more difficult to treat successfully?

* When treating follicular lymphoma, does the choice of chemotherapy regimen used in combination with immunotherapy matter, or are they all of similar efficacy?

* What is the role of radioimmunotherapy in the treatment of follicular lymphoma?

* How can response rates and overall survival (OS) in mantle-cellbe improved?

Warning: Leukine (sargramostim) recall
 
Audience: Oncologists, hematologists, other healthcare professionals
[Posted 01/24/2008] Bayer and FDA informed healthcare professionals of the market withdrawal of the current liquid formulation of Leukine, a growth factor that helps fight infection and disease in appropriate patients by enhancing immune cell function. The product was withdrawn because of an upward trend in spontaneous reports of adverse reactions, including syncope (fainting), which are temporally correlated with a change in the formulation of liquid Leukine to include edetate disodium (EDTA). The upward trend in adverse reaction reporting rates has not been observed with the use of lyophilized Leukine. Healthcare professionals should immediately stop using liquid Leukine and return unused vials to the manufacturer.

[January 23, 2008 - Dear Healthcare Professional Letter - Bayer Healthcare]

SGN-35 Investigational agent: Stock sale puts Seattle Genetics on solid ground seattlepi.nwsource.com 

In November, Seattle Genetics presented a study showing that SGN-35, an antibody linked to a drug to deliver it to target cells, had shrunk tumors in patients with Hodgkin's lymphoma. Siegall said Seattle Genetics would present "very exciting" SGN-35 data later this year and then present its plan to develop the treatment.

Expert Commentary: Areas of Confusion in Oncology  
What Is the Role of Maintenance Rituximab in Follicular NHL? cancernetwork.com/ 

David G. Maloney, Reviewed by John D. Hainsworth and Bertrand Coiffier
Should rituximab maintenance become standard therapy for follicular lymphoma?

DLBCL outcomes: Radiotherapy (RT) improves outcomes of early-stage DLBCL patients consultantlive.com/

"These are certainly very exciting findings and support the role of radiation therapy in patients with localized diffuse large B-cell lymphoma," said Dr. Ng, of the Dana-Farber Cancer Institute. She cautioned that patients who received more cycles of chemotherapy upfront or had a slow response to chemotherapy before starting radiation therapy may not have been recorded as receiving radiation therapy in SEER. 

"So there's a small potential concern that patients scored as receiving radiation therapy may represent a more favorable subgroup of patients, such as those having small, nonbulky disease or quicker response to chemotherapy so that less chemotherapy was given." This potential bias in favor of the radiation therapy cohort may limit the conclusions of the study, Dr. Ng commented. A possible workaround would be to repeat the analysis using the linked SEER Medicare database, which gives more detailed information, she pointed out. "Using this database, however, will limit the analysis to patients aged over 65," Dr. Ng said, "but this may be okay for this disease, which mainly affects older patients." 

fNHL outcomes: Long-term molecular remissions in patients with indolent lymphoma treated with rituximab as a single agent or in combination with interferon alpha-2a: A randomized phase II study from the Nordic Lymphoma Group. Leuk Lymphoma. 2008 Jan;49(1):102-12.  PMID: 18203019 

Extended rituximab is effective and well tolerated and combination with IFN seems to improve both the quality and duration of the responses, providing the opportunity to achieve long-term molecular CRs and prolonged failure-free survival without chemotherapy.

HL Outcomes: Superiority of reduced-intensity allogeneic transplantation over conventional treatment for relapse of Hodgkin's lymphoma following autologous stem cell transplantation. 
Bone Marrow Transplant. 2008 Jan 14;  PMID: 18195684 

These data demonstrate the potential efficacy of RIT in heavily pre-treated patients whose outlook with conventional therapy is dismal, and provide evidence of a clinically relevant graft-versus-lymphoma effect.

Expert background: Optimal Use of Prognostic Factors in NHL asheducationbook. 2006 pdf   

The management of non-Hodgkin lymphoma is complicated by wide heterogeneity within recognized subtypes. Patients with supposedly similar diagnoses can have remarkably varied clinical presentations, molecular profiles and clinical outcomes. Reliable prognostic markers could allow the identification of patient subsets that may benefit from alternate approaches.

Expert background: Reduced-Intensity Regimens in Allogeneic Stem-Cell Transplantation 
for NHL and CLL  asheducationbook 2006 pdf  

Rituxan maintenance? What Is the Role of Maintenance Rituximab in Follicular NHL? consultantlive.com

Dr. Hainsworth has conducted clinical research with funding received by the Sarah Cannon Research Institute from Genentech. 

Perhaps the most interesting and unexpected benefit of rituximab in the treatment of follicular lymphoma has been its use in maintenance therapy. The efficacy of this targeted agent in chronic therapy contrasts with the well documented futility of maintenance therapy using cytotoxic agents, and raises the possibility that the strategy underlying targeted-agent therapy may be fundamentally different.

Risk factors:  Treatment of Hepatitis C Reduces Incidence of Non-Hodgkin’s Lymphoma cancerconsultants.com

Researchers from Japan have reported that viral elimination in hepatitis C virus (HCV) infected patients reduces the incidence of non-Hodgkin’s lymphoma (NHL). The details of this study appeared in the December, 2007 issue of the American Journal of Medicine.

DLBCL outcomes: Rituximab Plus CHOP Boosts Survival in Older Lymphoma Patients medpagetoday.com 

The addition of rituximab improved three-year event-free survival from 47.2% with six cycles of CHOP and 53% with eight cycles to 66.5% and 63.1%, respectively, Michael Pfreundschuh, M.D., of Saarland University Medical School, and colleagues reported in the February issue of the Lancet Oncology.

Study Search: Clinical Trials for DLBCL and Radioimmunotherapy?  ClinicalTrials.gov

Outcomes /Press release: Zevalin Combined With High-Dose Chemotherapy and Autologous Stem-Cell Transplantation (ASCT) Produces High Overall Survival and Progression-Free Survival Rates in Patients With Relapsed Non-Hodgkin's Lymphoma  http://money.cnn.com 

produced a high rate (70 percent) of progression-free survival at two years without a significant increase in the toxicity of the HDC regimen underscoring the potential role for RIT in ASCT.

Side effects: Rituxan and Late-onset neutropenia (LON): Related abstracts http://www.ncbi.nlm.nih.gov

Outcomes Cutaneous T-cell: Stem cell transplantation for patients with primary cutaneous T-cell lymphoma.

... more than two-thirds of the allogeneic transplant recipients reported in the literature experienced long-term durable remissions of more than 3 years, which would appear superior to the expected median survival for such patients.

MCL cure? Mantle Cell Lymphoma Can Be Cured by Intensive Immunochemotherapy with In-Vivo Purged Stem-Cell Support; Final Report of the Nordic Lymphoma Group MCL2 Study  ASH abstracts2view.com 

Conclusion: The demonstration of long-term event-free survival in a large, consecutive prospective series now for the first time indicates that intensive immunochemotherapy including AraC and Rituximab with in-vivo purged stem-cell support may cure mantle cell lymphoma.

fNHL survival: Survival in Follicular Lymphoma: The Stanford Experience ASH 2007 abstracts2view.com 

Conclusions: OS of patients with FL managed at Stanford University significantly improved in the 1986-2003 eras, particularly among younger and advanced stage patients. 

MCL: A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma  bloodjournal.hematologylibrary.org 

According to the MIPI, patients were classified into low risk (44% of patients, median OS not reached), intermediate risk (35%, 51 months), and high risk groups (21%, 29 months), based on the 4 independent prognostic factors: age, performance status, lactate dehydrogenase (LDH), and leukocyte count. Cell proliferation (Ki-67) was exploratively analyzed as an important biologic marker and showed strong additional prognostic relevance. 

HL study of interest: Phase II Combination Clinical Trial With MGCD0103 and Vidaza® in Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma  marketwire.com  

"announced the enrollment of the first patient in a Phase II clinical trial (Trial 012) evaluating MGCD0103, the Companies' isotype-selective histone deacetylase inhibitor (HDACi) product candidate, in combination with Vidaza^® (azacitidine for injection), Pharmion's DNA demethylating agent, in patients with relapsed or refractory Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL).

Immune adjuvant: CPG-7909 (PF-3512676, ProMune^®): toll-like receptor-9 agonist in cancer therapy  expertopin.com 

Stimulation of toll-like receptor (TLR)9 activates human plasmacytoid dendritic cells and B cells, and induces potent innate immune responses in preclinical tumor models and in patients. CpG oligodeoxynucleotides (ODNs) are TLR9 agonists that show promising results as vaccine adjuvants and in the treatment of cancers, infections, asthma and allergy.

Related studies: ClinicalTrials.gov

Response marker for CLL: Serum globulins as marker of immune restoration after treatment with high-dose Rituxan for CLL PubMed 

An important biological alteration in chronic lymphocytic leukemia (CLL) is the dysregulation of immunoglobulin production, as a consequence of complex and yet incompletely understood interactions between plasma cells and the neoplastic B-cell clone. As a result, most patients develop severe hypogammaglobulinemia during the course of the disease.

anti-cd74 antibody: Immunomedics Patents  Internalizing Anti-CD74 Antibodies  Reuters  

The Company's lead anti-CD74 product candidate, milatuzumab, is a humanized antibody currently in Phase I/II studies for patients with multiple myeloma who have failed at least two prior standard systemic anti-myeloma treatment regimens. In addition, John P Leonard, MD, Weill Cornell Medical, is conducting a Phase I, open-label study in patients with recurrent non-Hodgkin's lymphoma or chronic lymphocytic leukemia funded in part by a grant from the National Cancer Institute.  

Related studies:  ClinicalTrials.gov

RIT and SCT review: Current status and future perspectives for Zevalin in stem cell transplantation for NHL

http://www.ncbi.nlm.nih.gov/ 

The preliminary data are highly promising in terms of conditioning tolerability and patient outcomes following transplant; further phase II studies are now needed to consolidate these data and to investigate specific patient populations and NHL subtypes.  PMID: 17922042 

Patient perspective: What NOT To Say To A Cancer Survivor  Kathy on WebMagic

Whether you are a newly diagnosed survivor or someone who loves him or her, cancer rocks your world. We survivors have our own issues to face, but those of you who care for us can help by learning what not to say. We know you mean well, but please avoid the following platitudes ....

CLL outcomes: Treanda™ (Bendamustine) Superior to Chlorambucil for Initial Treatment of CLL cancerconsultants.com:

Researchers from Germany have reported that Treanda (bendamustine) results in  higher response rates and improved progression-free survivals in patients with previously untreated Binet stage B and C chronic lymphocytic leukemia (CLL) compared to chlorambucil. 

Important: Cephalon Submits New Drug Application For TREANDA (Benamustine) medicalnewstoday.com

The TREANDA NDA for relapsed indolent NHL is supported by three studies in patients with NHL, including one in combination with rituximab. In these studies, patients treated with TREANDA had a high rate of response and a manageable and tolerable side effect profile, with adverse events similar to those observed with other chemotherapy agents.

cutaneous NHL: Radiotherapy Suitable for Most Primary Cutaneous B-Cell Lymphomas  cancerpage.com 

NEW YORK JAN 02, 2008 (Reuters Health) - Radiotherapy is appropriate for most patients with primary cutaneous B-cell lymphomas (CBCL), according to a recent Dutch study, but more aggressive treatment is needed in patients presenting with lesions on the leg.

Pilot CAM study: Jefferson scientists studying the effects of high-dose vitamin C on non-Hodgkin lymphoma patients http://www.eurekalert.org 

“This is a very unique study for a set of patients who have really run out of options,” said Daniel Monti, M.D., director of the Myrna Brind Center of Integrative Medicine, and primary investigator of the study. “Vitamin C administered intravenously has shown great promise in the laboratory and there has been some anecdotal data in cancer patients, but no one has really ever run a detailed study on humans. Vitamin C doesn’t cost much and is very low in toxicity, making it a particularly desirable agent for further study.”

CLL secondary risks: Risk for Second Neoplasms in Chronic Lymphocytic Leukemia  abkhazia.com 

"CLL is currently viewed as a long-term disease, for which most available treatments (with the exception of allogeneic transplantation) do not result in a cure. Awareness of physicians following these patients needs to be raised to the fact that significant morbidity and mortality stem not only from CLL itself, but also from superimposed processes, most notably infections and second malignancies."

CT risks: Debate continues about risks, and for which populations?  cancernetwork.com 

The authors recommend better equipment and techniques to lower radiation exposure and the alternative use of MRI and ultrasound, ***especially for infants and children.*** They urge physicians to avoid inappropriate CT utilization. ...  Arl Van Moore, Jr., MD, chair of the ACR board of chancellors, worried that patients may mistakenly avoid what the ACR characterized as "life-saving medical imaging care," because of the article. "They may be terribly confused and unduly distressed by some of the statements in this study," he said.

preclinical / interesting: New technique enhances binding avidity of monoclonal antibodies (MoAbs)  cancernetwork.com 

a humanized anti-CD20 MoAb enhanced with DXL technology, being developed for the treatment of non-Hodgkin's lymphoma.  The DXL technique involves modifying a MoAb by adding a small peptide sequence that becomes self-recognizing when two or more MoAb molecules are in close proximity. This self-binding property causes the modified antibodies to cluster at the target receptor, resulting in greater molecular mass on the surface of the target cell

Perspective on research obstacles: Why so many dead-end phase II trials? cancernetwork.com 

To expand evidence-based oncology care, we need to recognize the flaws in the drug development system so they can be corrected. As Dr. Tannock pointed out, self-aggrandizement among ambitious young researchers is one trend driving the troubling preponderance of dead-end phase II trials.

RIT at risk? Cell Therapeutics buys drug (Zevalin) shown to shrink tumors seattlepi.nwsource.com 

"In November, Medicare announced that it would cut back on its reimbursements of radioimmunotherapies, such as Zevalin, which can cost more than $20,000 to administer. An uproar ensued, and last week Congress passed legislation extending the previous reimbursement arrangement for six months."

fNHL outcomes: Genitope Corporation Reports Initial Results of Phase 3 Clinical Trial of MyVax(R) Personalized Immunotherapy genitope.com/

"We are excited by these results because the data clearly show that MyVax personalized immunotherapy is a safe and active drug for follicular lymphoma patients. Both arms of the trial appear to show activity. 

Patients who received MyVax personalized immunotherapy and mounted a positive immune response to the tumor-specific target demonstrated superior clinical outcomes compared to patients who did not mount this specific immune response. While we recognize that the regulatory path would be clearer had the trial met its primary endpoint, we are pleased with the outcome of the trial. We are working closely with the FDA to determine the path forward for MyVax personalized immunotherapy,"

CLL Outcomes:  Fludara (Fludarabine) Not Superior to Cytoxan (Chlorambucil) for Elderly with CLL cancerconsultants.com

involved 206 patients with CKK older than 64 years of age. Eighty-five percent of patients in this study were Binet stage B-C. The median age was 70 years.

Quality of Life: Cancer Docs Often Miss Patient Fears  webmd.com 

The researchers recorded close to 400 conversations between oncologists and patients and then counted how often the patients sought empathy from the doctors and how often the doctors responded empathetically to patient concerns. ... Showing support or asking patients to elaborate on their concerns, legitimizing the expressed emotion and praising patients for their strength were all considered empathetic responses.

CNS Prophylaxis: Central Nervous System (CNS) Relapse in Aggressive Non-Hodgkins Lymphoma; Does CNS Prophylaxis Work?    abstracts2view.com

Conclusion: CNS relapse almost always occurs within 2 years of initial treatment, is usually isolated, and portends a poor prognosis. Patients with > 1 extranodal sites or those having a high IPI score have a higher incidence of CNS relapse. There is no evidence to suggest however, that CNS prophylaxis with either cranial radiation or intrathecal MTX/Ara-C decreases the risk of CNS relapse.

aggressive NHL Outcomes: DOSE- ESCALATED CHOP AND TAILORED INTENSIFICATION WITH IFE ACCORDING TO EARLY RESPONSE IN POOR RISK AGGRESSIVE B CELL LYMPHOMA: A PROSPECTIVE STUDY FROM THE GEL-TAMO STUDY GROUP.  Abstract

No different outcomes were observed between patients achieving an early negative Ga (67)S response treated with MegaCHOP and BEAM/ ASCT and patients with midtreatment positive Ga (67)S who received IFE prior BEAM/ ASCT. Conclusions: This response adapted strategy including early treatment modifications prior HDT/ ASCT have yielded encouraging PFS and OS in patients with poor risk aggressive NHL.

CLL treatment decisions: What Is the Optimal Initial Treatment for Chronic Lymphocytic Leukemia?  cancernetwork.com/
THOMAS S. LIN, MD, PhD 

"The choice of initial therapy for an individual patient should depend upon the patient's age and medical condition, cytogenetic and other prognostic factors, and whether the goal of therapy is maximization of CR and PFS or palliation of symptoms with minimal toxicity."

HD Outcomes (small study): mTOR Inhibition (everolimus) for Relapsed or Refractory Hodgkin Lymphoma: Promising Single Agent Activity with Everolimus (RAD001). ASH Poster Session

Oral everolimus has promising activity with acceptable toxicity in Hodgkin lymphoma. These results provide the rationale for additional studies with this novel class of agents and to integrate mTOR inhibitors into salvage treatment regimens for Hodgkin lymphoma.

Angioimmunoblastic L Outcomes: High-Dose Therapy (HDT) and Autologous Stem-Cell Transplantation (ASCT) in Angioimmunoblastic Lymphoma: Complete Remission at Transplantation Is the Major Determinant of Outcome  J Clin Oncol. 2007 Dec 10;   PMID: 18071187 

This study shows that HDT and ASCT offers the possibility of long-term disease-free survival to patients with AITL. Early transplantation is necessary to achieve optimal results.

fNHL Prognostic marker: Biologic predictors in follicular lymphoma: Importance of markers of immune response. Leuk Lymphoma. 2007 Dec;48(12):2403-11. PMID: 18067016 

PTCL Prognostic marker: Expression of CYP3A4 as a predictor of response to chemotherapy in peripheral T-cell lymphomas. Blood. 2007 Nov 1;110(9):3345-51. Epub 2007 Jul 18. PMID: 17634410 

In conclusion, a high CYP3A4 tumoral expression could be useful to predict poor response to the standard PTCL chemotherapy; in these cases alternative chemotherapy combinations or doses should be explored.

aggressive NHL Outcomes: Two Studies Demonstrate REVLIMID (R) (lenalidomide) Activity In Patients With Relapsed/Refractory Aggressive Non-Hodgkin's Lymphoma  - medilexicon.com 

"The data from these studies are encouraging in that they show an impressive response to REVLIMID in relapsed/refractory, aggressive NHL," said John Leonard, M.D., The Richard T. Silver Distinguished Professor of Hematology Medical Oncology at Weill Cornell Medical College. "These data justify a wide exploration of REVLIMID in a variety of lymphoma settings both alone and in combination, and warrant a detailed assessment of which patients can particularly benefit."

indolent / MCL Outcomes: Bendamustine Plus Rituximab Versus CHOP Plus Rituximab in the First-Line Treatment of Patients with Indolent and Mantle Cell Lymphomas First Interim Results of a Randomized Phase III Study of the StiL abstracts2view.com 

Results: So far 439 patients have been randomized. 273 patients are evaluable for response for this first interim analysis (B-R: n=139; CHOP-R: n=134). Median patient age is 63 years. Histologies are equally distributed between arms: follicular 52%, mantle cell 20%, and other indolent lymphomas 28% in both treatment groups, each. The ORR for pts treated with B-R was similar to that associated with CHOP-R (94% vs 93%, respectively). CR was also similar at 51% for B-R compared to 40% for CHOP-R. The median observation time for both groups is 17 months. Thus far, 15 deaths have been observed (B-R: 7; CHOP-R: 8). Progressive or relapsed disease has been documented during the follow-up period: 27 in pts treated with B-R and 32 in the CHOP-R group. The B-R regimen appears to have a better toxicity profile, as evidenced by a lower rate of total alopecia (40% CHOP-R vs. 0% with B-R) and a lower number of infectious complications (41 in CHOP-R pts vs. 19 in the B-R group).

relapsed NHL Outcomes: "Mini" Allogeneic stem cell transplantation can induce durable clinical and molecular remissions in relapsed lymphomas: pre-transplant disease status and histotype heavily influence outcome. 

CTCL - Interim outcome: ASH: Forodesine HCl active single oral agent for advanced refractory CTCL - abstracts2view.com 

Forodesine is a rationally designed, potent inhibitor of purine nucleoside phosphorylase (PNP) that leads to intracellular accumulation of dGTP and then apoptosis. ... Conclusion: Oral forodesine demonstrates clinical activity in subjects with refractory CTCL, including those with SS, with minimal toxicity to date. 

Cure word used: Mini-BMT: follicular Non-Hodgkin's Lymphoma Cure? http://www.webmd.com/

83% in Complete Remission 5 to 9 Years After Mini-BMT for Follicular Lymphoma

ASH report on MDS: Oral Glutathione Analogue TLK199 Safe and Effective in Patients With MDS

NHL Risk factors: Sun exposure, vitamin D receptor gene polymorphisms and risk of non-Hodgkin lymphoma. Abstract

"Recent findings suggest that ultraviolet (UV) radiation exposure may reduce risk of developing non-Hodgkin lymphoma (NHL), but the biologic basis for this relationship remains unclear."

Improved bone marrow biopsy: FDA Clears Use of Novel Bone Marrow Biopsy System for Oncology http://biz.yahoo.com/bw/071207/20071207005110.html?.v=1

"Necessary for the diagnosis and management of lymphoma, leukemia, myeloma and other hematological disorders, bone marrow biopsy has historically been very painful for patients. The Vidacare system enables the clinician performing the procedure to quickly and precisely enter the intraosseous space, successfully capture a core, with minimal patient discomfort or pain." 

Comment: Also may improve clinical trial participation and utilization of radioimmunotherapies (Bexxar / Zevalin)

CLL: TREANDA New Drug Application for the Treatment of Chronic Lymphocytic Leukemia Granted Priority Review Status by FDA

CLL: National Cancer Institute Study To Determine The Optimal Time For CLL Patients To Begin Treatment
Main Category: Lymphoma / Leukemia News Article Date: 05 Dec 2007 - 0:00 PST

The multi-center study will include 1,700 newly diagnosed patients with chronic lymphocytic leukemia (CLL) and is designed to test the hypothesis that early treatment of patients with certain negative risk factors leads to longer survival. Genzyme will perform the IgVH mutation analysis for the study.

Preclinical imaging: New scan charts cancer treatment success - telegraph.co.uk 

A cool way to improve the sensitivity of body scanners more than 10,000 fold could allow cancer patients to see whether their tumours are being killed within days of treatment.

 ...chemical, called pyruvate, which cancer cells use to generate energy, has been cooled to near absolute zero and then heated rapidly again to change its magnetic properties and make it much more visible to the radio waves used by the machine, a so called magnetic resonance imaging scanner.

Professional Background: Antibody Therapy in Aggressive Lymphomas - asheducationbook.hematologylibrary.org 

Targeted therapies with monoclonal antibodies and monoclonal antibodies conjugated to radioimmunoconjugates have altered the natural history and the approach to treatment of aggressive non-Hodgkin lymphomas.

Outcomes: Chemotherapy Plus Radiation Recommended as Standard of Care in Early Hodgkin’s - professional.cancerconsultants.com

Patient Perspectives on the issue of transfer of tissue for clinical use – particularly for use in translational clinical research - PDF 

"... we may not have fully considered that requests for transfer of tissue for clinical use could many times be in harmony with the ultimate objective of achieving “personalized medicine ...” 

Preclinical/hopeful: Radio Waves Fire Up Nanotubes Embedded In Tumors, Destroying Liver Cancer ScienceDaily (Nov. 1, 2007)  sciencedaily.com

— Cancer cells treated with carbon nanotubes can be destroyed by non-invasive radio waves that heat up the nanotubes while sparing untreated tissue, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center and Rice University has shown in preclinical experiments.

Study of interest: Participate in the Genome Expression Study  & Background
(highly recommended when it's time for a biopsy)

Rationale: The observed variability in the clinical course of follicular lymphoma, along with 
the diverse range of therapeutic options available, necessitates accurate prognostic 
stratification of the individual patient.

Questionable ethics: Low dose Naltrexone for lymphomas?  Why we are skeptical   

Early Determination Of Effectiveness Of Cancer Treatment [for DLBCL] Using PET Imaging - medicalnewstoday.com

"In our study, we demonstrated that a quantitative assessment of therapeutic response for patients with diffuse large B-cell lymphoma (DLBCL) is more accurate than visual analysis alone when using the radiotracer FDG

Pilot study: High activity [escalating doses of] Zevalin® with peripheral blood progenitor cells support [followed by ASCT]  in patients with refractory/resistant B-cell non-Hodgkin lymphomas  blackwell-synergy.com/  

... high-activity Zevalin^® with ASCT is feasible and could be safely delivered in elderly and heavily pretreated NHL patients, including those who previously received high-dose chemotherapy and ASCT.

Prognostic factors in childhood anaplastic large cell lymphoma : results of a large European Intergroup Study. Blood. 2007 Oct 23; PMID: 17957029

... three factors associated with an increased risk of failure in childhood ALCL have been defined: 
mediastinal involvement, visceral involvement and skin lesions.

Prognostic factors: Cytochrome P450 2C19 loss-of-function polymorphism is associated with an increased treatment-related mortality in patients undergoing allogeneic transplantation. Bone Marrow Transplant. 2007 Oct;40(7):659-64. Epub 2007 Aug 6. PMID: 17680025 

Comment: Probably this finding needs to be validated (reproduced by an independent group) before being declared as true, but it shows how normal variations in patients (a polymorphism) can affect outcomes.  In this case, treatment-related mortality is strongly correlated with a specific normal genetic variation 

CNS lymphoma: Brain parenchyma involvement as isolated central nervous system (CNS) relapse of systemic non-Hodgkin lymphoma: an International Primary CNS Lymphoma Collaborative Group report.
Blood. 2007 Oct 25; PMID: 17962515 

Our results suggest systemic methotrexate is the optimal treatment for isolated CNS relapse involving the brain parenchyma. Long-term survival is possible in some patients.

Side effects: Cognitive function recovers after stem cell transplant - oncolink.org 

To investigate, the researchers initially studied 286 patients who were randomized to be tested pre-transplant and 6 and 12 months, and another 124 were tested at 6 and 12 months. Eighty-three patients who were tested at 12 months only were not included in the analysis.

MCL prognostic factors: A new prognostic index (MIPI) for patients with advanced stage mantle cell lymphoma. Blood. 2007 Oct 25;  PMID: 17962512

According to the MIPI, patients were classified into low risk (44% of patients, median OS not reached), intermediate risk (35%, 51 months), and high risk groups (21%, 29 months), based on the four independent prognostic factors: (1) age,  (2) ECOG performance status, (3) LDH and leukocyte count. 

Cell proliferation (Ki-67)  was exploratively analyzed as important biological marker and showed strong additional prognostic relevance. 

CLL Technical: State-of-the-art treatment of chronic lymphocytic leukemia -  ehaweb.org  pdf  Jun 2007

This review attempts to summarize the best developments today in the initial management of CLL.

Outcomes: A phase I/II study of galiximab (an anti-CD80 monoclonal antibody) in combination with Rituxan for relapsed or refractory, follicular lymphoma. Ann Oncol. 2007 Jul;18(7):1216-23. Epub 2007 Apr 29. PMID: 17470451 

73 patients received treatment. All had received at least one prior lymphoma therapy; 40% were rituximab naive. Infusions were delivered in an outpatient setting and were well tolerated. The most common study-related adverse events (AE) were lymphopenia, leukopenia, neutropenia, fatigue, and chills. The overall response rate at the recommended phase II dose of galiximab (500 mg/m(2)) was 66%: 19% complete response, 14% unconfirmed complete response, and 33% partial response. The median progression free survival was 12.1 months.

Living well: Barbara Held - A Positive Outlook is Overrated (NPR article)

I believe that there is no one right way to cope with all of the pain of living. 
As an academic psychologist, I know that people have different temperaments, 
and if we are prevented from coping in our own way, be it "positive" or "negative," we function less well.

mini allo SCT outcomes: Allogeneic stem cell transplantation following reduced-intensity conditioning (RIC) can induce durable clinical and molecular remissions in relapsed lymphomas: pre-transplant disease status and histotype heavily influence outcome nature.com  

Relapse risk differed significantly at 3 years between follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL) (14 versus 46%, P=0.04). Molecular remission occurred in 94 and 40% (P=0.002) of patients with FL and CLL, respectively. 

On multivariate analysis, OS was influenced by chemorefractory disease (hazard ratio (HR)=3.6), diagnosis of HD (HR=3.5), and acute GVHD (HR=5.9). RIC allogeneic SCT is a feasible and effective salvage strategy in both indolent and aggressive NHL

CNS outcomes: Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2007 Oct 20;25(30):4730-5. PMID: 17947720

The addition of rituximab to MPV increased the risk of significant neutropenia requiring routine growth factor support. Additional cycles of R-MPV nearly doubled the CR rate. Reduced-dose WBRT was not associated with neurocognitive decline, and disease control to date is excellent.

Treatment-related ri Individualized estimates of second cancer risks after contemporary radiation therapy for Hodgkin lymphoma. Cancer. 2007 Oct 16; PMID: 17941006 

Contemporary IFRT is predicted to substantially reduce risk of secondary breast and lung cancer compared with mantle RT, with considerable variation in risk among individuals. Individualized prospective risk estimates could facilitate patient-specific counseling and the development of more effective RT techniques.

Outcomes: Rituxan in relapsed lymphocyte-predominant Hodgkin Lymphoma: Long-term results of a phase-II trial of the German Hodgkin Lymphoma Study Group (GHSG). Blood. 2007 Oct 15; PMID: 17938252 

"Thus, rituximab is highly effective in relapsed and refractory NLPHL. This study is registered at http://www.klinisches-studienzentrum.de/trial/285 "

Expert review Autologous transplantation for follicular lymphoma? Not too soon! - bloodjournal.hematologylibrary.org/ 

The overall role of ASCT in follicular lymphoma continues to be debated. It is an excellent treatment option for the management of younger patients with recurrent disease.⁴ In advanced newly diagnosed lymphoma, a survival advantage has yet to be shown; with more prolonged follow-up it may still emerge in the GLSG study.

Novel cd20 antibody: 3^rd Generation Humanized Type II CD20 Antibody - ASH 2006

"significantly enhanced efficacy in a variety of in vitro and in vivo preclinical models. GA101 constitutes the first type II CD20 antibody successfully engineered for increased ADCC. Based on these data, GA101 is a promising therapeutic antibody candidate for the treatment of B-cell malignancies."

Sponsor-based trial news: Accentia Biopharmaceuticals Announces Unblinding and Analysis of Fast Tracked Phase 3 Trial for BiovaxID (idiotype vaccine for follicular lymphoma)  - businesswire.com/ 

Based on their review of the available data, the DMC recommended implementation of a data lock on the clinical trial data to take effect in September 2007 and requested that an interim analysis of the study’s efficacy endpoints and overall safety profile be performed. Accordingly, the Company has temporarily halted recruitment, randomization, and treatment in the phase 3 trial pending the analysis of the unblinded data. The Company anticipates providing BiovaxID to any patients randomized on an unblinded basis pursuant to a compassionate use exemption.

Life style guidance: ASCO Expert Corner: Talking With Your Child About His or Her Cancer PLWC.org 

Children frequently understand a great deal more than we as parents or caretakers realize and give them credit for. Withholding information from a child who can sense the anxiety and fear in his or her parents and other family members substantially increases their own fear and anxiety. It is important to be open and honest and share as many facts ...

RIT and risk of MDS: Treatment-related myelodysplastic syndrome (MDS) and AML in patients treated with Zevalin radioimmunotherapy. J Clin Oncol. 2007 Sep 20;25(27):4285-92. Epub 2007 Aug 20.
PMID: 17709799 

Analysis of data from patients ... (746 patients) ... incidences of t-MDS and t-AML (0.7% per year after treatment) are consistent with that expected in patients with NHL who have had extensive previous chemotherapy treatment and do not appear to be increased after treatment with the ibritumomab tiuxetan regimen.

CLL prognostic factors: Assessment of CLL and SLL by absolute lymphocyte counts in 2,126 patients: 
20 years of experience at the University of Texas M.D. Anderson Cancer Center.
J Clin Oncol. 2007 Oct 10;25(29):4648-56. PMID: 17925562 

Deletion 17p or 6q with or without other cytogenetic abnormalities, 
age at least 60 years, 
beta2-microglobulin at least 2 mg/L, 
albumin less than 3.5 g/dL, and 
creatinine at least 1.6 mg/dL 
 
were each found to independently predict shorter survival

Feasibility study: Study of radiolabeled indium-111 and Zevalin in primary central nervous system lymphoma. Cancer. 2007 Oct 11; PMID: 17932895 

The results from this study suggest that it may be feasible to deliver radiolabeled monoclonal anti-CD20 antibodies as a component of therapy for PCNSL.

A high tumor-associated macrophage (TAM) content predicts favorable outcome in follicular lymphoma patients treated with R-CHOP  citeulike.org

Consistent with previous studies, high TAM amount was associated with adverse outcome in chemotherapy-treated patients (P = 0.026). ... The data [from this study] suggest that high TAM score is associated with a favorable prognosis in FL patients treated with immunochemotherapy.

Words from 'The Lymphoma Files' - billingsgazette.net 

"The concern," my doctor says, "is that this may be lymphoma."

My doctor's good. He knows you don't just drop a big old piece of information in someone's lap like that and let the awkward silence fill the room, so he launches into a brief spiel on ... I'm not sure what. I haven't heard anything since the word "lymphoma."

Prognostic factors & auto SCT: The pre-transplant FLIPI Index is associated with survival of follicular lymphoma patients undergoing autologous stem cell transplantation.
Leuk Lymphoma. 2007 Oct;48(10):1961-7. PMID: 17917964 

The association of FLIPI with survival appeared to be more relevant for patients who received standard conditioning regimens compared to those that were treated with high-dose radioimmunotherapy (p = 0.004). 

Among all patients, mortality was also associated with chemosensitive disease (HR = 0.47, p = 0.01) or untreated relapse (HR = 0.20, p = 0.0002) vs. chemo-resistant disease, 
and >/=2 extranodal sites (HR = 2.82, p = 0.03) after adjusting for FLIPI. 

These data suggest that the FLIPI and select non-FLIPI factors after adjustment for the FLIPI are associated with survival in FL patients undergoing ASCT.

Hot item for T-cell lymphoma: Pralatrexate, a novel class of antifol with high affinity for the reduced folate carrier-type 1, produces marked complete and durable remissions in a diversity of chemotherapy refractory cases of T-cell lymphoma. Br J Haematol. 2007 Nov;139(3):425-8. PMID: 17910632 

All four patients with T-cell lymphoma (TCL) achieved a complete remission. Patients with B-cell lymphoma achieved stable disease at best. For each TCL patient, the response was more durable than their best response with chemotherapy. This early experience is the first to document this unique activity of pralatrexate in TCL.

Outcome SCT:Outcomes after allogeneic hematopoietic cell transplantation with nonmyeloablative or myeloablative conditioning regimens for treatment of lymphoma and chronic lymphocytic leukemia. 
Blood. 2007 Oct 4; PMID: 17916744 

Patients with comorbidities experienced lower treatment related mortality (p=0.009) and better survival (p=0.04) after nonmyeloablative (mini) conditioning.

Harvesting stem cells: Intermediate dose etoposide plus G-CSF 16 g/kg is more effective than cyclophosphamide 4 g/m(2) plus G-CSF 10 g/kg in PBSC mobilization of lymphoma patients.
Leuk Lymphoma. 2007 Oct;48(10):1950-60. PMID: 17917963 

Intermediate dose etoposide + G-CSF 16 microg/kg is a highly effective mobilizing therapy, further, it has the advantage of low hematologic toxicity and can be easily administered as outpatient treatment.

Background: Genetic vaccines - Google books

Education: NCI Guidance: Chemotherapy and You - Cancer.gov | PDF

Education: NCI Guidance: Radiotherapy and You - Cancer.gov | PDF

Education: NCI Radiation Therapy Fact Sheet Series - Cancer.gov 

Education: NCI Facing Forward: Life After Cancer Treatment - Cancer.gov | PDF 

Education: NCI Caring for the Caregiver: Support for Cancer Caregivers - Cancer.gov | PDF

Education: NCI Taking Part in Cancer Treatment Research Studies - Cancer.gov | PDF

Outcome report on GVHD: Treatment of steroid-resistant acute GVHD with OKT3 and high-dose steroids results in better disease control and lower incidence of infectious complications when compared to high-dose steroids alone: a randomized multicenter trial by the EBMT Chronic Leukemia Working Party.
Leukemia. 2007 Aug;21(8):1830-3. Epub 2007 May 10. No abstract available. PMID: 17495972

Case report on safety: Vision loss following denileukin diftitox treatment: a case report of possible posterior ischemic optic neuropathy. Leuk Lymphoma. 2007 Apr;48(4):808-11. No abstract available. PMID: 17454642

Improving SCT with RIT: Radioimmunotherapy and stem-cell transplantation in the treatment of aggressive B-cell lymphoma. Leuk Lymphoma. 2007 Sep 19;:1-11  PMID: 17891639  

Radio-labeled antibodies are ideal candidates to combine with high-dose chemotherapy and ASCT. Their major toxicity is myelosuppression, which is easily reversed by ASCT and they can target disease sites with almost no added toxicity to normal tissues. RIT has been used in escalated doses as the sole treatment prior to ASCT or in standard or escalated doses combined with standard high-dose chemotherapy regimens. RIT was also combined with reduced-intensity conditioning and allogeneic SCT. 

Preliminary results are promising and suggest improved disease control with no added toxicity; however randomized studies are needed to confirm these initial observations.

New treatment target: FCRL1 on chronic lymphocytic leukemia, hairy cell leukemia and B-cell non-Hodgkin's lymphoma as a target of immunotoxins. Blood. 2007 Sep 25;  PMID: 17895404 

Investigational vaccine for cutaneous lymphomas:  Transgene.fr | ClinicalTrials.gov

TG 1042's antitumoral activity relies on the secretion of human IFNγ from tumor cells adenovirally-transduced with the nucleotidic sequence encoding the cytokine. IFNγ is a natural immunostimulant produced in the body, whose antitumoral properties were demonstrated both in animals and in humans.

...a high rate of local clinical responses : 55% of 31 evaluable patients responded to the treatment with nine complete responses (CR) and eight partial responses (PR). Out of the 26 patients with cutaneous T-cell lymphoma (CTCL) 46% responded (six CR and six PR), and 100% of the five patients with cutaneous B-cell lymphoma (CBCL) responded to the TG1042 treatment (three CR and two PR) :

These results suggest that intralesional therapy with TG 1042 represents a non-toxic and effective treatment for CBCL.

Patient Education: Dr. Vose on Treating lymphomas

The replay of today’s lymphoma program has been posted here: patientpower.info  
Direct link to Webcast (voice only):  patientpower.info

First line Campath for CLL:  FDA Approves Expanded Labeling For Campath® To Include First Line Treatment For CLL  medicalnewstoday.com  

"The data that supported this label expansion add to a growing body of evidence about the effectiveness of Campath across the entire CLL treatment pathway," stated Mark Enyedy, president of Genzyme's oncology business unit. "A broader range of patients is now eligible for Campath treatment, regardless of whether they have received prior therapy. The approval also marks an important step in a long-term development plan that is exploring the full potential of Campath in high-risk CLL, combination and consolidation therapy."

Long term risks: Effect of prior rituximab on high-dose therapy and autologous stem cell transplantation in follicular lymphoma. Bone Marrow Transplant. 2007 Sep 17; PMID: 17873917 

these results suggest that the use of rituximab-based regimens for the treatment of FL does not compromise the effectiveness of HDT and ASCT as a salvage strategy in patients with FL.

Lymphoma Awareness Quiz: Know your nodes: http://www.knowyournodes.org.nz/index.php 

Leukemia and Blood foundation: Now is the time to get to ‘know your nodes’, and find out just how important your lymphatic system is.

Outcome data:  Interim Response and Safety Analyses Support Continuation of PDX (pralatrexate) in Patients with Peripheral T-Cell Lymphoma  money.cnn.com

Results of the interim analysis of patient response data exceeded the pre-specified threshold for continuation of the trial, which required a minimum of four responses (complete or partial) out of the first 35 evaluable patients, as determined by independent oncology review.

Treatment complications: Antifungal Treatment Delays Responsible For Excess Deaths From Fungal Infection: Presented at ICAAC 

"Among patients who received effective therapy within 6 hours of hypotension onset, the in-hospital survival rate exceeded 60%, with no marked difference between types of infection. Survival rates for both fungal and bacterial infection decreased dramatically as treatment delays grew longer."

Vaccine news: Favrille: The Wall Street Analyst Forum Presentation Transcript  seekingalpha.com 

We initiated this trial in July of 2004 and we closed the two enrollments in January of 2006 just 18 months later with 349 randomized patients in the trial. 18 months is very fast for an oncology trial, and our investigators tell us that, essentially patients were self enrolling into this trial because they really like the concept of two biologic therapies and being able to avoid chemotherapy at this point.

Hats off! High Resolution Analysis of Follicular Lymphoma Genomes - bcgsc.ca | data & privacy info

High resolution analysis follicular lymphoma genomes to discover the genomic rearrangements contributing to development of follicular lymphoma and the additional rearrangements contributing to the progression from follicular lymphoma to diffuse large B cell lymphoma.

HATS OFF to the project leaders!

Dr. Marco Marra  | Dr. Joseph Connors | Randy Gascoyne |  Dr. Adrienne Drobnies
 

Preclinical: Polymorphism in clinical immunology – From HLA typing to immunogenetic profiling 

The pathology of humans, in contrast to that of inbred laboratory animals faces the challenge of diversity addressed in genetic terms as polymorphism. Thus, unsurprisingly, treatment modalities that successfully can be applied to carefully-selected pre-clinical models only sporadically succeed in the clinical arena.

Perspective on treatment goals: Radioimmunotherapy of follicular lymphoma: a step towards cure?
Bull Cancer. 2007 Sep 1;94(9):799-806. French.  PMID: 17878100 

From the therapeutic point of view, we argue that the debate should not be as to which one among antibody immunotherapy or RIT should be best added to chemotherapy, but that all three treatments might be optimally combined with the aim to get the highest chance of cure for advanced stage follicular lymphoma.

Quality of Life: Cancer patients, spouses report similar emotional distress, U-M study finds eurekalert.org/

Interventions should be targeted to spouses along with patients

The researchers urge more health care interventions aimed at emotional distress for both patients and caregivers. At the same time, caregivers should recognize they too are emotionally affected by this illness and seek appropriate support. Patients also can play a role by encouraging their spouse to be actively involved in their care. 

Imaging: caIMAGE: Enabling Standardization and Collaboration - cabig.cancer.gov 

Greater reliance on imaging in clinical care and biomedical research, the current structure of clinical studies, and other advances in technology have led to an enormous increase in the quantity and complexity of cancer imaging data. Despite this increase, however, there is little standardization of protocols used to acquire, analyze, and annotate images among cancer centers and other research facilities.

Perspective: Phase I to III Trials of Anti B Cell Therapy in Non Hodgkin's Lymphoma.
Clin Cancer Res. 2007 Sep 15;13(18):5636s-42s. PMID: 17875800

Newer agents are being engineered to target novel antigens, and to interact more specifically with the host immune system. These promising therapeutics face a significant challenge in evaluation and integration in the post-rituximab world.

Outcome data:  Multicenter study of i.v. Bu/Cy/E as conditioning regimen for autologous stem cell transplantation in patients with non-Hodgkin's lymphoma. Bone Marrow Transplant. 2007 Sep 10; PMID: 17846602  

In conclusion, the conditioning regimen of i.v. Bu/Cy/E was well tolerated and seemed to be effective in patients with aggressive NHL

Preclinical: A novel proteoliposomal vaccine elicits potent antitumor immunity in mice.
Blood. 2007 Jun 15;109(12):5407-10. Epub 2007 Mar 9. PMID: 17351111 

Here we describe a novel vaccine formulation prepared by simply extracting cell-membrane proteins from lymphoma cells and incorporating them together with IL-2 into proteoliposomes.  ... The vaccine elicited T-cell immunity in vivo, as demonstrated by secretion of type 1 cytokines. It protected against tumor challenge at doses of tumor antigen 50 to 100 times lower than that previously observed using either liposomes formulated with IL-2 and secreted lymphoma immunoglobulin or a prototype vaccine consisting of lymphoma immunoglobulin conjugated to keyhole limpet hemocyanin.

Quackery:  Life Rife Frequency Generator - healthwatcher.net 

Although unanimously condemned as wort