Non-cutaneous Peripheral T-cell Lymphoma Research Articles

Real-Life Experience Regarding Clinical Characteristics and Treatment Outcome in Non-Cutaneous Peripheral T-Cell Lymphomas: A Multicenter Study of the Turkish Hematology Research and Education Group (ThREG)

Objective:Peripheral T-cell lymphomas (PTCLs) are an uncommon and quite heterogeneous group of disorders, representing only 10%-15% of all non-Hodgkin lymphomas. Although both molecular and clinical studies have increased in recent years, we still have little knowledge regarding real-life practice with PTCLs. In this study, we aimed to investigate the clinical characteristics and treatment outcomes of a large population-based cohort of patients presenting with systemic non-cutaneous PTCL.Materials and Methods:We conducted a multicenter retrospective analysis of 190 patients consecutively diagnosed and treated with non-cutaneous PTCLs between 2008 and 2016.Results:Considering all first-line treatment combinations, the overall response rate was 65.9% with 49.4% complete remission (n=81) and 16.5% partial response (n=27). The 5-year overall survival and event-free survival rates were significantly different between the transplant and non-transplant groups (p<0.01, and p=0.033, respectively).Conclusion:The retrospective analysis of a large volume of real-life data on the Turkish experience regarding non-cutaneous PTCL patients showed consistent results compared to other unselected PTCL cohorts with some minor differences in terms of survival and transplantation outcomes. The long-term outcome of patients who receive autologous hematopoietic cell transplantation as part of upfront consolidation or salvage therapy is favorable compared to patients who are unable to receive high-dose therapy.

Lymphomatoid papulosis mimicking relapsed angioimmunoblastic T-cell lymphoma on histology: the importance of clinicopathological correlation.

Angioimmunoblastic T-cell lymphoma (AITL) is one of the commonest subtypes of peripheral T-cell lymphoma (PTCL) world-wide and the most common non-cutaneous PTCL in Western Europe. Despite aggressive chemotherapy +/- consolidation autologous stem cell transplant relapse occurs in >50% of cases which is either treated aggressively with high dose chemotherapy followed by allogeneic transplant or with therapy aimed at producing prolonged disease control.1 Biopsy of relapsed disease is essential as a subset may be complicated by a B-cell (often EBV+) lymphoproliferation. Histological progression may occur with a monomorphic/'tumour cell rich' appearance rather than the polymorphous appearance seen in typical AITL.2.

Plitidepsin: design, development, and potential place in therapy.

Plitidepsin is a cyclic depsipeptide that was first isolated from a Mediterranean marine tunicate (Aplidium albicans) and, at present, is manufactured by total synthesis and commercialized as Aplidin®. Its antitumor activity, observed in preclinical in vitro and in vivo studies has prompted numerous clinical trials to be conducted over the last 17 years, alone or in combination with other anticancer agents. Single-agent plitidepsin has shown limited antitumor activity and a tolerable safety profile in several malignancies, such as noncutaneous peripheral T-cell lymphoma, melanoma, and multiple myeloma. In patients with relapsed or refractory multiple myeloma, plitidepsin activity seems to be enhanced after addition of dexamethasone while remaining well tolerated, and a Phase III trial comparing plitidepsin plus dexamethasone vs dexamethasone alone is underway. Additional studies are required to better define the role of plitidepsin in combination with other active agents in these indications. Results of plitidepsin activity in other hematological malignancies or solid tumors have been disappointing so far. Further studies analyzing its mechanisms of action and potential biomarkers will help select patients who may benefit most from this drug. In this review, we critically analyze the published studies on plitidepsin in hematological malignancies and solid tumors and discuss its current role and future perspectives in treating these malignancies. We also review its design, pharmaceutical data, and mechanism of action.

Radiation Therapy In Peripheral T-Cell Lymphoma Of The Head and Neck

IntroductionThe role of radiation therapy in peripheral T-cell lymphoma (PTCL) is not well established. While the NCCN guidelines recommend combined modality treatment with consolidative radiation therapy after chemotherapy for localized (stage I and II) disease, the data supporting this recommendation is lacking and is extrapolated from B-cell lymphoma. MethodsThis is a retrospective analysis of outcome in patients with non-cutaneous peripheral T-cell lymphoma of the head and neck from the Surveillance, Epidemiology and End Results (SEER) database diagnosed between 1981-2010. Survival was estimated by Kaplan-Meier estimates using the log-rank test. Univariate and multivariable analyses were performed using Cox regression analysis. ResultsOf the 307 patients analyzed, 130 (43%) underwent radiation therapy. The median age was 59 years old, 60.3% were male, 73.9% were Caucasian and the median year of diagnosis was 2004. The majority of patients had PTCL, Not Otherwise Specified (74.3%), followed by anaplastic large cell histology (22.2%). Patients were grouped as stage I (47.2%), stage II (29.9%) and stage III/IV (22.8%). Head and neck sites included the nasal cavity (28.3%), oropharynx (25.7%), oral cavity (21.2%), salivary gland (11.7%), nasopharynx (7.8%) and larynx/hypopharynx (5.2%).The median follow-up was 54 months for survivors. Radiation therapy was associated with a higher 5-year overall survival in all patients (56.7% vs. 38.4%, p=0.001), patients with stage I disease (63.4% vs. 53.4%, p=0.036) and patients with stage II disease (60.8% vs. 36.3%, p=0.034), see Figure 1. Radiation therapy was not associated with a difference in overall survival in patients with stage III/IV disease (p=0.91). [Display omitted] Univariate analysis demonstrated that age, stage, radiation therapy and marital status were predictive of overall survival, but sex, and race were not. The year (p=0.93) or decade of treatment (p=0.67) did not impact overall survival. On multivariable analysis, increasing age (HR: 1.02, p<0.001), increasing stage (HR: 1.42, p=0.004), radiation therapy (HR: 0.60, p=0.011) and marital status of not married (HR: 1.49, p=0.035) remained statistically significant predictors of overall survival.An additional analysis was performed excluding patients who survived less than 3 months to account for mortality related to disease progression or chemotherapy toxicity. After excluding these 45 patients, radiation therapy was still associated with increased overall survival in all patients (p<0.001) and in patient with limited stage disease (p=0.021). ConclusionsThe integration of local radiation therapy to the treatment of PTCL of the head and neck may improve overall survival in patients with limited stage disease. Disclosures:No relevant conflicts of interest to declare.

Multicenter phase II study of plitidepsin in patients with relapsed/refractory non-Hodgkin's lymphoma

This phase II clinical trial evaluated the efficacy, safety and pharmacokinetics of plitidepsin 3.2 mg/m(2) administered as a 1-hour intravenous infusion weekly on days 1, 8 and 15 every 4 weeks in 67 adult patients with relapsed/refractory aggressive non-Hodgkin's lymphoma. Patients were divided into two cohorts: those with non-cutaneous peripheral T-cell lymphoma (n=34) and those with other lymphomas (n=33). Efficacy was evaluated using the International Working Group criteria (1999). Of the 29 evaluable patients with non-cutaneous peripheral T-cell lymphoma, six had a response (overall response rate 20.7%; 95% confidence interval, 8.0%-39.7%), including two complete responses and four partial responses. No responses occurred in the 30 evaluable patients with other lymphomas (including 27 B-cell lymphomas). The most common plitidepsin-related adverse events were nausea, fatigue and myalgia (grade 3 in <10% of cases). Severe laboratory abnormalities (lymphopenia, anemia, thrombocytopenia, and increased levels of transaminase and creatine phosphokinase) were transient and easily managed by plitidepsin dose adjustments. The pharmacokinetic profile did not differ from that previously reported in patients with solid tumors. In conclusion, plitidepsin monotherapy has clinical activity in relapsed/refractory T-cell lymphomas. Combinations of plitidepsin with other chemotherapeutic drugs deserve further evaluation in patients with non-cutaneous peripheral T-cell lymphoma. (clinicaltrials.gov identifier: NCT00884286).

Upfront VIP‐reinforced‐ABVD (VIP‐rABVD) is not superior to CHOP/21 in newly diagnosed peripheral T cell lymphoma. Results of the randomized phase III trial GOELAMS‐LTP95

Peripheral T-Cell lymphomas (PTCL) are relatively rare diseases but appear to be highly aggressive and display worse remission and survival rates than B-cell lymphomas. Despite unsatisfactory results with the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen, it remains the reference front-line therapy in these diseases, but has not been challenged in phase III trials. The Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang (GOELAMS) devised an alternative therapeutic schedule including etoposide, ifosfamide, cisplatin alternating with doxorubicin, bleomycin, vinblastine, dacarbazine (VIP-reinforced-ABVD; VIP-rABVD) and compared it to CHOP/21 as front-line treatment in non-cutaneous PTCL. All newly diagnosed patients were eligible. The primary objective was to improve the 2-year event-free survival (EFS) rate. Secondary objectives were to compare the response rate, overall survival, and toxicities as well as identify prognostic factors. Eighty-eight patients were identified between 1996 and 2002. Both arms were well balanced for patients' characteristics in terms of histological and clinical presentation. No significant difference was observed between the two arms in terms of 2-year EFS. Anaplastic large cell lymphoma type and Ann Arbor stage I-II were identified as two independent favourable prognostic factors influencing survival. VIP-rABVD was not superior to CHOP/21 in terms of EFS as first-line treatment of PTCL, confirming that CHOP/21 remains the reference regimen in these lymphomas.

Clinicopathologic Characteristics of HIV-Associated Peripheral T-Cell Lymphoma.

Abstract 3924Poster Board III-860 IntroductionThe incidence of lymphomas is increased in HIV-infected individuals. Most of the cases are B-cell subtypes of non-Hodgkin lymphoma. Although the incidence of mature or peripheral T-cell lymphomas (PTCL) seems to be increased in HIV-positive cases, clinicopathological data is lacking. The objective of this study is to describe the characteristics of non-cutaneous PTCL in HIV-infected individuals and identify potential prognostic factors. MethodsInstitutions within and outside of the United States were invited to submit original data on cases of HIV-associated PTCL. Data on each case included country of origin, age, sex, ethnicity, CD4 count, use of highly active antiretroviral therapy (HAART), B symptoms, lymphoma subtype according to the WHO classification of lymphoid neoplasms, expression of ALK, EBV and Ki-67, T-cell gene rearrangement, number of extranodal sites, bone marrow involvement, clinical stage, performance status, lactate dehydrogenase (LDH) levels, frontline therapy, response, use of stem cell transplantation (HSCT), final outcome, survival in months and cause of death; these will be presented using descriptive statistics. Univariate analyses were performed using Kaplan-Meier survival estimates compared using the log-rank test. Cox proportional-hazard regression test was used for the multivariate analysis. P-values of less than 0.05 were considered significant. ResultsThus far, data on 24 cases have been obtained from 7 institutions. From these cases, 13 (54%) are from South America, 5 (21%) from Europe, 3 (12.5%) from North America and 3 (12.5%) from Asia. Thirteen cases (54%) are Hispanic, 5 (21%) are Caucasian, 3 (12.5%) are Black and 3 (12.5%) are Asian. Median age is 39 years (range 26 to 58 years) and the male-to-female ratio is 7:1. Sixteen cases (70%) presented with B symptoms. Median CD4 count is 129 cells/mm3 (range 4 to 305 cells/mm3). Twelve cases (63%) reported use of HAART. Fourteen cases (58%) are PTCL, unspecified (PTCLU), 4 cases (17%) anaplastic large cell lymphoma (ALCL), 4 cases (17%) of NK/T-cell lymphoma (NKTCL) and 2 cases (8%) angioimmunoblastic lymphoma (AITL). All ALCL cases were ALK-negative; EBV was expressed in 50% of NKTCL cases but in none of the AITL cases. Four of 15 cases (27%) had involvement of more than 2 extranodal sites, 3 of 11 cases (27%) had bone marrow involvement, 19 of 24 cases (79%) presented with advanced stage, 5 of 12 cases (42%) had an elevated LDH level and 8 of 24 cases (33%) had a performance status higher than 2. Thirteen of 24 cases (54%) were treated with chemotherapy alone from which 8 cases (62%) received CHOP therapy; six of 24 cases (25%) did not receive any therapy. Nine of 14 cases (65%) responded to therapy (29% CR and 36% PR); 35% of cases did not respond to therapy. Five cases of 14 (36%) underwent HSCT; 4 cases (29%) in the frontline and 1 case (7%) in the salvage setting. At the time of this report, 63% of cases have died; 53% due to infectious complications and 40% due to lymphoma progression. The median survival for the group was 10 months. The median survival for treated (n=19) and untreated cases (n=5) were 10.5 and 1 month, respectively (p=0.005). ConclusionsHIV-associated PTCL tends to affect younger men with CD4 counts of less than 200 cells/mm3. PTCLU is the most common subtype reported in HIV-infected individuals. HIV-associated ALCL cases do not appear to express ALK. The survival of treated HIV-associated PTCL cases is short at 10.5 months despite a 65% initial response to therapy. Accumulation of data continues. Disclosures:No relevant conflicts of interest to declare.

Management of rare forms of lymphoma

The recent Revised European-American Classification of Lymphoma (REAL) classification system has been shown to allow easy, accurate, and reproducible identification of several clinically distinctive lymphoma subtypes. Many of these well-recognized lymphoma entities are relatively rare, as shown by a recent large survey of more than 1400 non-Hodgkin's lymphoma (NHL) cases from eight different countries. The purpose of this article is to summarize the present information known about these less common entities. Particular attention will be paid to the management problems of the following subtypes: the marginal-zone B-cell lymphomas of nodal type (or monocytoid lymphoma, comprising 1.8% of total cases in the above-mentioned series), the extranodal marginal-zone B-cell lymphomas (or mucosa-associated lymphoma tissue [MALT] lymphomas, representing 7.6% of the cases), the splenic marginal-zone B-cell lymphomas (< 1% of cases), the mantle cell lymphomas (6% of cases), and the primary mediastinal large B-cell lymphomas (2.4% of cases). Also, the main non-cutaneous peripheral T-cell lymphoma types, which including the natural killer (NK) disorders comprise less than 12% of all lymphoma cases, are discussed.

Peripheral T-cell lymphoma: a clinicopathological study of 41 cases and evaluation of the prognostic significance of the updated Kiel classification.

A total of 41 non-cutaneous peripheral T-cell lymphomas were classified following the updated Kiel classification. Of these, 20 cases belonged to the low-grade group (T-cell chronic lymphocytic leukaemia, 3; lymphoepithelioid, 5; angioimmunoblastic, 4; pleomorphic small cell, 8) and 21 to the high grade group (pleomorphic medium and large cell, 11; immunoblastic, 3; large-cell anaplastic Ki-1 positive, 7). Seventy per cent showed a CD4+/CD8-phenotype, 39% a defective phenotype and 88% an activation phenotype. Eighty per cent had B-symptoms, 63% hepatomegaly, 48% splenomegaly and 26% had involvement of more than three lymphoid areas. Bone marrow was infiltrated in 34%, central nervous system in 4%, lung in 12% and skin in 14.6%. Seventeen per cent presented with extranodal disease and 82.8% had stage III/IV disease. Hypergammaglobulinaemia was found in 29%, hypercalcaemia in 7%, raised LDH serum levels in 58% and HTLV-I antibodies in only one case. Of the 37 treated patients 18 (48%) achieved a complete remission, but 33% relapsed. Mortality was 59% and actuarial overall survival at 38 months was 0.32. In the comparison of the clinical, analytical and immunophenotypic variables and outcome between low and high grade groups, only the average of bone marrow infiltration in the low grade and stage I-II, presence of defective phenotypes and higher Ki-67 positivity in the high grade group were significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytogenetic abnormalities in noncutaneous peripheral T-cell lymphoma

Cytogenetic studies were performed on lymph nodes from eight patients with noncutaneous peripheral T-cell lymphoma. At least one chromosomally abnormal clone was identified in each patient. Chromosomes having structural abnormalities in two or more patients included chromosome #1 (four), chromosome #2 (three), chromosome #4 (two), chromosome #8 (two), chromosome #14 (two), and chromosome #17 (two). The abnormal clones from seven patients had structural abnormalities involving either chromosomes #1 or #2, and the eighth patient had an abnormal clone that was trisomic for chromosome #1. We did not observe structural rearrangements in chromosome #14 at bands q11 or q12 in any of our cases, in contrast to previous suggestions that this chromosomal region may play a critical role in the development of T-cell lymphomas. Our findings suggest that other nonrandom chromosome abnormalities are common and may be important in the development of non-cutaneous peripheral T-cell lymphomas.