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Updates
 In the News:
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Oncology Times: PTCL: Should Initial Management Include
High-Dose Therapy with Autologous Stem Cell Rescue?
http://bit.ly/15nsV5x |
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
References
and News
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NEW 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.
Background Resources
PubMed queries on PCTL
Clinical Trials
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. |
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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 |
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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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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.
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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