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Types of Lymphoma > T-cell > Peripheral T-cell Lymphoma

Last update: 04/21/2014

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Background Resources | Topic Searches | Clinical Trials |
Treatment Updates | PET for T-cell lymphoma?

In the News

Introduction

Lymphoma is a blood cell cancer - a condition where abnormal lymphocytes (a type of white blood cell) expand in number forming tumors often in lymph nodes but also in other regions, such as the bone marrow.  See lymphatic system and Lymphoma Simplified.

Peripheral T-cell lymphomas describes a diverse group of blood cancers that originate from T-cells, which may be at various stages of  development. 

These lymphomas usually presents at diagnosis in stage III or IV, and often has an aggressive clinical course requiring prompt treatment. 

Histologies include (non-cutaneous): 
 
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PTCL = peripheral t-cell lymphoma, NOS = Not otherwise specified

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AITL = Angioimmunoblastic T-cell lymphoma 

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ALCL = Anaplastic large cell lymphoma

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Enteropathy associated T-cell lymphomas

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NK lymphoma (NK = Natural Killer Cell)

Source: NCCN.org  PDF (login req.)

Incidence: More frequent in adults than children. Low incidence - approximately 10-15% of non-Hodgkin's lymphoma. Account for about 12% of lymphoid tumours worldwide.  Uncommon in North America. Peripheral T-Cell Lymphoma Unspecified is the most common group. Also see specific variants (subtypes), below.  

Grade:  aggressive clinical course.

Staging: Staging refers to the how widespread the disease is. Imaging tests (CT MRI, PET, Gallium). See Staging for more detail.

Diagnosis requires analysis of tissue sample using a variety of tests to identify the cell type.  T-cell markers will "express CD4 or CD8, but not both." 1

Prognosis:  Each lymphoma is unique and the prognosis can depend on many clinical factors, including the unique molecular and biological characteristics of the tumor, the patient's age, general health and immune status, areas of involvement, how widespread the disease is at diagnosis (stage), and if so-called b-symptoms are present. 

Also see Prognostic Markers for articles on biomarkers that may predict risk of disease

Treatment:  Combination chemotherapy, such as CHOP, followed by stem cell transplantation.  For investigational approaches, see below.  

"Although CHOP remains the standard front-line therapy for PTCL, given these poor outcomes, most PTCL patients (with the exception of ALK-positive ALCL) should be considered for clinical trials of initial therapy." 2

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PET for aggressive T-cell lymphoma?

* ASH Paper:
Negative Interim FDG-PET Scan Is Predictive of Superior Outcome in T Cell Lymphoma http://bit.ly/1iDzGpb

* Prognostic Value of Interim and Posttherapy 18F-FDG PET/CT in Patients with Mature T-Cell and Natural Killer Cell Lymphomas http://bit.ly/QsitVu 

Our study indicates that interim and posttherapy PET/CT results are 2 independent predicators of PFS and OS in T/NK-cell lymphomas. In addition, our data also imply that patients with positive results at interim or post therapy PET/CT should be considered candidates for an intensive therapeutic strategy to improve their clinical outcome.

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References and News

* Br J Haematol 2013:
A phase I/II trial of bortezomib combined concurrently with gemcitabine for relapsed or refractory DLBCL and peripheral T-cell lymphomas. http://1.usa.gov/1dvY1sd 

Whereas efficacy of this combination was low in heavily pre-treated DLBCL, there was a signal of activity in relapsed/refractory PTCL utilizing the modified schedule.
* Am J Hematol 2013:
The aggressive peripheral T-cell lymphomas: 2013. http://1.usa.gov/1ic7OJB
References:
  1. Treatment policy prepared by Dr. Kirsty Tompkins  www.tsrcc.on.ca T-Cell.pdf 
     
  2. A Systematic Review and Meta-Analysis of Front-line Anthracycline-Based Chemotherapy Regimens for Peripheral T-Cell Lymphoma http://bit.ly/qFmamM

    ABSTRACT:

    Anthracycline-based chemotherapy remains standard treatment for peripheral T-cell lymphoma (PTCL) although its benefits have been questioned.

    We performed systematic literature review and meta-analyses examining the complete response (CR) and overall survival (OS) rates for patients with PTCL.

    The CR rate for PTCL patients ranged from 35.9% for enteropathy-type T-cell lymphoma (ETTL) to 65.8% for anaplastic large cell lymphoma (ALCL).

    The 5-year OS was 38.5% for all PTCL patients and ranged from 20.3% for ETTL to 56.5% for ALCL.

    These data suggest that there is marked heterogeneity (variation in outcomes) across PTCL subtypes in the benefits of anthracycline-based chemotherapy.

    While anthracyclines produce CR in half of PTCL patients, this yields reasonable 5-year OS for patients with ALCL but not for those with PTCL-NOS (not-otherwise specified) or ETTL.

    Novel agents and regimens are needed to improve outcomes for these patients.


    CONCLUSION OF AUTHORS:

    "Despite achieving CR with front-line anthracycline-based therapy in more than half of PTCL patients, 5-year OS remains poor for most PTCL subtypes.

    Although CHOP remains the standard front-line therapy for PTCL, given these poor outcomes, most PTCL patients (with the exception of ALK-positive ALCL) should be considered for clinical trials of initial therapy.

    Future clinical trials need to focus on subtype-specific treatment, incorporation of newer agents, and non-anthracycline-based combinations to improve the long-term outcome for PTCL patients.

    Moreover, strategies capable of sustaining responses such as maintenance therapy and transplant consolidation should be actively investigated in prospective clinical trials. Given the small number of PTCL patients seen by any single institution, such trials need to be multi-centered and community oncologists should encourage their patients to enroll in such studies whenever available.

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Background Resources  

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NEW RESOURCE: PTCL, ASH Education Program Book, 2011:
Therapies for Peripheral T-Cell Lymphomas Kerry J. Savage 
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Leukemia: Allogeneic transplantation following a reduced-intensity conditioning regimen in relapsed/refractory peripheral T-cell lymphomas: long-term remissions and response to donor lymphocyte infusions support the role of a graft-versus-lymphoma effect
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PTCL, ASH Education Program Book, 2011:
Therapies for Peripheral T-Cell Lymphomas Kerry J. Savage 
"...Encouragingly, there have been several new therapies emerging with activity in PTCLs and exciting novel combinations under consideration that will hopefully move the field forward and improve outcome in this challenging group of diseases."
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About PTCL:

DoctorsDoctor | ASCO slide presentation | cancerbacup.org.uk
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PDQ -- for Health Professionals  NIH
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Peripheral T-Cell Lymphomas: Classification and Treatability:

Interview With Dr. James O. Armitage, 2010 oncologystat.com
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Extranodal types  hmds.org.uk
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Peripheral T cell lymphoma, not otherwise specified: the stuff of genes, dreams and therapies pubmedcentral.nih.gov/  (full text - technical)
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Gene expression profiling identifies molecular subgroups among nodal peripheral T-cell lymphomas. Oncogene. 2006 Mar 9;25(10):1560-70. PMID: 16288225

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Also see Guidelines at diagnosis
for a checklist that pertains to all types of lymphoma.
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Medscape Topic search:  Medscape (free login required)
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Towards understanding the peripheral T-cell lymphomas
annonc.oxfordjournals.org (full text)

Some studies have shown that patients with relapsed aggressive peripheral T-cell lymphoma respond to autologous hematopoietic stem cell transplantation as well as do those with relapsed diffuse large B-cell lymphoma [17–19]. This has led many clinicians to offer transplant in first remission to patients with high-stage peripheral T-cell lymphoma. A number of newer agents have been shown to benefit some patients with relapsed peripheral T-cell lymphoma and need to be tested as possible primary therapy.
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PubMed queries on PCTL

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 Diagnosis | Review | Therapies | Prognosis
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Clinical Trials

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ClinicalTrials.gov studies for

Previously Untreated PTCL:
http://bit.ly/f0LALB  

Relapsed PTCL: http://bit.ly/dRSOak
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Treatment Updates

 
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Summary of NCCN Guidelines 2011 
See for details: nccn.org pdf (requires free subscription and login)

First-primary treatment
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Clinical Trial preferred - Lookup:
Previously Untreated PTCL:
http://bit.ly/f0LALB  

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CHOP for ALCL, ALK+ subtype

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Other regimens to consider:
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CHOP, then ICE

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CHOP, then IVE

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HyperCVAD

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First-line consolidation (such as transplant)
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All patients except low risk, or ALCL, ALK+ with good prognosis.

Second-line treatment (relapse setting) transplant eligible
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Clinical Trial preferred - Lookup:
Relapsed PTCL: http://bit.ly/dRSOak

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Transplant following:
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DHAP /  ESHAP / GDP / GemoOx / ICE / MINE

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Pralatrexate (but not for AITL subtype)

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Romidepsin

Second-line treatment (relapse setting) not eligible for transplant:
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Clinical Trial preferred - Lookup:
Relapsed PTCL: http://bit.ly/dRSOak

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Alemtuzumab (activity in small trial)

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Bortezomib (activity in small trial)

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Cylosporine for AITL subtype only

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Denileukin Diftitox / Gemcitabine / Radiation therapy

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Pralatrexate (but not for AITL subtype)

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Romidepsin
 

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Treatment policy prepared by Dr. Kirsty Tompkins  www.tsrcc.on.ca T-Cell.pdf 
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Peripheral T cell lymphoma, not otherwise specified: the stuff of genes, dreams and therapies pubmedcentral.nih.gov/  (full text - technical)
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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
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Autologous transplantation for relapsed or primary refractory peripheral T-cell lymphoma. http://bit.ly/yYvN9 

"With a median follow-up time of 6 years for surviving patients with PTCL and DLBCL, the 5-year progression-free survival (PFS) rates for PTCL and DLBCL patients were 24% and 34% respectively (P = 0.14); the corresponding overall survival (OS) rates were 33% and 39% respectively. There were no significant differences between the two groups with respect to time to disease progression or survival after progression." 
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Also see Long-term results of autologous hematopoietic cell transplantation for peripheral T cell lymphoma: the Stanford experience. www.ncbi.nlm.nih.gov/pubmed/18541192  

"Disease status at AHCT had a significant impact on PFS and OS. The 5-year PFS for patients in CR1/PR1, CR2/PR2+, and REF was 51%, 12%, and 0%, respectively, and the corresponding figures for OS were 76%, 40%, and 30%, respectively. The pretransplant factors that impacted survival were disease status and the number of prior regimens. Histology, age, sex, stage, B symptoms, bone marrow involvement, and duration of first response did not significantly affect PFS or OS."
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Phase II trial of denileukin diftitox (Ontak) for relapsed/refractory T-cell non-Hodgkin lymphoma interscience.wiley.com 

"Objective responses (six CRs, seven PRs) were achieved in 13 patients (48·1%), stable disease in eight (29·6%) and six (22·2%) had progressive disease. An objective response was achieved in eight of 13 patients (61·5%) with CD25+ tumours (four CR/four PR) and five of 11 patients (45·5%) with CD25 tumours (two CR/three PR). Median progression-free survival was 6 months (range, 1–38+ months). Most adverse reactions were grade 1/2 and transient. No grade 4–5 toxicities were reported. Denileukin diftitox had significant activity and was well tolerated in relapsed/refractory T-NHL, with responses observed in both CD25+ and CD25 tumours. Further studies of denileukin diftitox in combination with other agents are warranted in previously untreated and relapsed/refractory T-NHL."
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Therapy with gemcitabine in pretreated peripheral T-cell lymphoma patients annonc.oxfordjournals.org  

"Of the 13 patients, one achieved complete response (CR) and eight achieved partial responses (PR); the remaining four showed no benefit from the treatment. Among the responders, one CR and four PR were documented in the PTCLU patients and four PR in MF patients. Treatment was well tolerated; hematologic toxicity was mild and no nausea/vomiting or organ toxicity was recorded."
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Review: Hematopoietic SCT for peripheral T-cell lymphoma?
Bone Marrow Transplant. 2008 Oct 20. PMID: 18936735
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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.

Gleevec (imatinib) in Relapsed/Refractory T Cell Non-Hodgkin's Lymphoma ClinicalTrials.gov
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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.
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Interim Response and Safety Analyses Support Continuation of PDX (pralatrexate) in Patients with Peripheral T-Cell Lymphoma  www.earthtimes.org

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.
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Frontline Autologous Stem Cell Transplantation (Asct) In High-Risk Peripheral T-Cell Lymphoma (PTCL): A Prospective Study From The Gel-Tamo Study Group  blackwell-synergy.com 

Results: CR was achieved by 12 patients (46%) after 3 courses of MegaCHOP and 12 patients received IFE as a salvage therapy. After the ASCT (n=19), 89% of patients achieved CR. In contrast, 6 patients (23%) did not receive the transplant due to the progression of the disease (n=5) or lethal toxicity (n=1). One patient in first-line CR refused ASCT. 

After a median follow-up of 35 months, the OS and PFS at 3 years was 73% and 53%, respectively. Moreover, the OS, PFS and DFS were 84%, 56% and 63%, respectively 2 years after transplant in the patients who received ASCT consolidation (n=19). 

Conclusions: Early salvage therapy for patients with high-risk aggressive nodal PTCL that do not achieve CR after 3 courses of chemotherapy and ASCT frontline consolidation for chemosensitive patients may improve treatment outcome.
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Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation.
Leukemia. 2006 Sep;20(9):1533-8. Epub 2006 Jul 27. PMID: 16871285 

... our findings indicate (1) up-front high-dose therapy and ASCT are feasible, but could induce a high rate of long-term CR only in patients with ALK-positive ALCL and (2) the achievement of CR before autografting is a strong predictor of better survival."
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Autologous transplantation for relapsed or primary refractory peripheral T-cell lymphoma.
Br J Haematol. 2006 Jun 6; PMID: 16759221
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Marker Expression in Peripheral T-Cell Lymphoma: A Proposed Clinical-Pathologic Prognostic Score.
J Clin Oncol. 2006 Apr 24; PMID: 16636342
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Gene expression profiling identifies molecular subgroups among nodal peripheral T-cell lymphomas.
Oncogene. 2006 Mar 9;25(10):1560-70. PMID: 16288225
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Direct comparisons of peripheral T-cell lymphoma with diffuse B-cell lymphoma of comparable histological grades--should peripheral T-cell lymphoma be considered separately? jco.org 
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Stem cell transplantation for peripheral T-cell lymphomas. 
Leuk Lymphoma. 2004 Mar;45(3):441-6. Review. PMID: 15160904
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Peripheral T-cell lymphomas unspecified presenting in the skin: analysis of prognostic factors in a group of 82 patients. Blood. 2003 Sep 15;102(6):2213-9. Epub 2003 May 15. PMID: 12750155 | More
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Peripheral T-cell lymphoma (excluding anaplastic large-cell lymphoma): results from the Non-Hodgkin’s Lymphoma Classification Project  Annals of Oncology 13:140-149, 2002
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Clinical features of peripheral T-cell lymphomas in 78 patients diagnosed according to the Revised European-American lymphoma (REAL) classification.
Eur J Cancer. 2002 Jan;38(1):75-81. PMID: 11750843  PubMed
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Peripheral T-cell lymphoma [NK-type] Curr Oncol Rep. 2002 Sep;4(5):434-42. Review. PMID: 12162919  PubMed
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Inhibitor of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T-cell lymphoma: a case report.  Blood. 2001 Nov 1;98(9):2865-8. PMID: 11675364  PubMed

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In the News:

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Novel therapies for peripheral T-cell lymphomas (full text) ncbi.nlm.nih.gov

Accumulating data indicate that these novel agents have little cumulative toxicity and can be administered continuously to patients who are not candidates for consolidative stem-cell transplantation (SCT), with little impact on quality of life. They might also provide a new salvage option for patients eligible for SCT with no impact on autologous stem-cell collection or subsequent engraftment.
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Oncology Times: PTCL: Should Initial Management Include High-Dose Therapy with Autologous Stem Cell Rescue?
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