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Lymphomation.org > Current News > 2006/7 Archived News Items -

2006/7
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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 
About Post Traumatic Stress Disorder http://www.medicinenet.com 

"Posttraumatic stress disorder (PTSD) is an emotional illness that develops as a result of a terribly frightening, life-threatening, or otherwise highly unsafe experience. PTSD sufferers re-experience the traumatic event or events in some way, tend to avoid places, people, or other things that remind them of the event (avoidance), and are exquisitely sensitive to normal life experiences (hyperarousal). "
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/
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.