The outcome of peripheral T-cell lymphoma patients failing first-line therapy: a report from the prospective International T-Cell Project.
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ABSTRACT:
SUBMITTER: Bellei M
PROVIDER: S-EPMC6442952 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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The outcome of peripheral T-cell lymphoma patients failing first-line therapy: a report from the prospective International T-Cell Project.
Bellei Monica M Federico Massimo M
Haematologica 20190401 4
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Project description:This analysis explored factors influencing survival of patients with primary refractory and relapsed peripheral T-cell lymphomas enrolled in the prospective International T-cell Project. We analyzed data from 1020 patients with newly diagnosed disease, enrolled between September 2006 and December 2015. Out of 937 patients who received first-line treatment, 436 (47%) were identified as refractory and 197 (21%) as relapsed. Median time from the end of treatment to relapse was 8 months (range 2-73). Overall, 75 patients (8%) were consolidated with bone marrow transplantation, including 12 refractory and 22 relapsed patients. After a median follow up of 38 months (range 1-96 months) from documentation of refractory/relapsed disease, 440 patients had died. The median overall survival (OS) was 5.8 months; 3-year overall survival rates were 21% and 28% for refractory and relapsed patients, respectively (P<0.001). Patients receiving or not salvage bone marrow transplantation had a 3-year survival of 48% and 18%, respectively (P<0.001). In a univariate Cox regression analysis, refractory disease was associated with a higher risk of death (HR=1.43, P=0.001), whereas late relapse (>12 months, HR 0.57, P=0.001) and salvage therapy with transplantation (HR=0.36, P<0.001) were associated with a better OS. No difference was found in OS with respect to histology. This study accurately reflects outcomes for patients treated according to standards of care worldwide. Results confirm that peripheral T-cell lymphomas patients had dismal outcome after relapse or progression. Patients with chemotherapy sensitive disease who relapsed after more than 12 months might benefit from consolidation bone marrow transplantation.
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Project description: Not available
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Project description:Peripheral T-cell lymphoma accounts for about 10% of all cases of non-Hodgkin's lymphoma. However, less than 5% of patients with non-Hodgkin's lymphoma present with hypercalcaemia as the initial symptom, and less than 1% present with primary bone lesions. We herein describe a 76-year-old Chinese man who was diagnosed with primary bone adult T-cell lymphoma with extensive osteolysis, including bone loss in the radius, as the initial manifestation. He had developed severe generalised bone pain and an inability to raise his arms. X-ray examination revealed osteolytic destruction of the forearm with loss of the radial diaphysis. The patient was diagnosed with peripheral T-cell lymphoma based on his immunohistochemical results. He began treatment with the CHOPE chemotherapy regimen, which resulted in significant improvement of his bone pain.
| S-EPMC8524712 | biostudies-literature
Project description:The natural history of limited-stage peripheral T-cell lymphomas (PTCLs) remains poorly defined. We investigated outcomes and prognostic variables in patients registered in the T-Cell Project (TCP) (#NCT01142674) to develop a model to predict overall survival (OS) for the common nodal PTCL subtypes (PTCL-NOS, AITL, ALCL). The model was validated in an independent data set from Australian and Brazilian registries. 211 patients registered in the TCP between 2006-2018 were studied. The median age was 59 years (range 18-88) and median follow-up was 49 months. One hundred twenty-seven patients (78%) received anthracycline-based regimens, 5 patients (3%) radiotherapy alone (RT), 24 patients (15%) chemotherapy+RT. 5-year OS and PFS were 47% and 37%, respectively. Age >60 years, elevated LDH and low serum albumin were independent prognostic factors. The model identified 3 groups with low- (26%, score 0), intermediate- (41%, score 1), and high-risk (33%, score 2-3) with 5-year OS of 78% (95% confidence interval [95% CI], 29-127), 46% (95% CI, 24-68), and 25% (95% CI, 20-30), respectively (P < 0.001) and 5-year PFS of 66% (95% CI, 33-99), 37% (95% CI, 9-65), and 17% (95% CI, 9-25), respectively (P < 0.001). The model demonstrated greater discriminatory power than established prognostic indices and an analogous distribution and outcomes in the 3 groups in the validation cohort of 103 patients. The SALENTO Model (Limited Stage Peripheral T-Cell Lymphoma Prognostic Model) is an objective, simple and robust prognostic tool. The high-risk group has poor outcomes, comparable to advanced stage disease, and should be considered for innovative first-line approaches.
| S-EPMC10471929 | biostudies-literature
Project description:Angioimmunoblastic T-cell lymphoma (AITL) is a unique subtype of peripheral T-cell lymphoma (PTCL) with distinct clinicopathologic features and poor prognosis. We performed a subset analysis of 282 patients with AITL enrolled between 2006 and 2018 in the international prospective T-cell Project (NCT01142674). The primary and secondary end points were 5-year overall survival (OS) and progression-free survival (PFS), respectively. We analyzed the prognostic impact of clinical covariates and progression of disease within 24 months (POD24) and developed a novel prognostic score. The median age was 64 years, and 90% of patients had advanced-stage disease. Eighty-one percent received anthracycline-based regimens, and 13% underwent consolidative autologous stem cell transplant (ASCT) in first complete remission (CR1). Five-year OS and PFS estimates were 44% and 32%, respectively, with improved outcomes for patients who underwent ASCT in CR1. In multivariate analysis, age ≥60 years, Eastern Cooperative Oncology Group performance status >2, elevated C-reactive protein, and elevated β2 microglobulin were associated with inferior outcomes. A novel prognostic score (AITL score) combining these factors defined low-, intermediate-, and high-risk subgroups with 5-year OS estimates of 63%, 54%, and 21%, respectively, with greater discriminant power than established prognostic indices. Finally, POD24 was a powerful prognostic factor with 5-year OS of 63% for patients without POD24 compared with only 6% for patients with POD24 (P < .0001). These data will require validation in a prospective cohort of homogeneously treated patients. Optimal treatment of AITL continues to be an unmet need, and novel therapeutic approaches are required.
| S-EPMC8493974 | biostudies-literature
Project description:Peripheral T-cell lymphomas (PTCLs) have an aggressive biological course and poor clinical outcomes. Despite producing somewhat less-than-satisfactory results, the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) remains the de facto standard in PTCL treatment. Addition of etoposide to CHOP backbone to overcome such unsatisfactory results has yielded contradictory information. We aimed to thoroughly analyze the impact of incorporating etoposide into first-line treatment. Using merged data from the Korean National Health Insurance Service and National Cancer Registry, a total of 1933 patients (median age, 58 years) were evaluated for clinical characteristics and treatment outcomes. Thirty-eight percent (n = 748) of the 1933 patients received CHOP or CHOP-like regimen, 35.1% (n = 678) received CHOP-like regimen plus etoposide, 5.9% (n = 113) received other backbone chemotherapy plus etoposide, and 20.3% (394) received other treatments in the first-line setting. When we divided the patients into 3 groups according to regimen (group 1, CHOP or CHOP-like regimen; group 2, CHOP or CHOP-like regimen plus etoposide; group 3, all others), group 1 was associated with longest progression-free survival (PFS; P < .001) and overall survival (OS; P < .001). This lack of benefit with etoposide addition was observed across different PTCL subtypes and age groups. Adding etoposide led to longer hospitalizations and cytopenias requiring more transfusion. Upfront hematopoietic stem-cell transplantation led to better OS. Addition of etoposide to CHOP-like regimens does not result in better PFS or OS for patients with PTCL. Overall, Asian patients with PTCL do not benefit from chemotherapy intensification of first-line treatment. We hereby provide crucial information on establishing standardized PTCL treatment.
| S-EPMC5737133 | biostudies-literature
Project description:In November 2018, the U.S. Food and Drug Administration (FDA) approved brentuximab vedotin (BV) for the treatment of adult patients with previously untreated systemic anaplastic large cell lymphoma or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone (CHP). Approval was based on ECHELON-2, a randomized, double-blind, actively controlled trial that compared BV+CHP with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in 452 patients with newly diagnosed, CD30-expressing PTCL. Efficacy was based on independent review facility-assessed progression-free survival (PFS). The median PFS was 48.2 months with BV+CHP versus 20.8 months with CHOP, resulting in a hazard ratio (HR) of 0.71 (95% confidence interval [CI]: 0.54-0.93). The trial also demonstrated improvement in overall survival (HR 0.66; 95% CI: 0.46-0.95), complete response rate (68% vs. 56%), and overall response rate (83% vs. 72%) with BV+CHP. The most common adverse reactions (incidence ≥20%) observed ≥2% more with BV+CHP were nausea, diarrhea, fatigue or asthenia, mucositis, pyrexia, vomiting, and anemia. Peripheral neuropathy rates were similar (52% with BV+CHP, 55% with CHOP). Through the Real-Time Oncology Review pilot program, which allows FDA early access to key data, FDA granted this approval less than 2 weeks after official submission of the application. IMPLICATIONS FOR PRACTICE: This is the first U.S. Food and Drug Administration approval for treatment of patients with newly diagnosed peripheral T-cell lymphomas (PTCL). Improvement in progression-free and overall survival over cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, which has been the standard of care for decades, is unprecedented. The new regimen represents a major advance for the frontline treatment of patients with CD30-expressing PTCL.
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Project description:PurposeNatural killer (NK) cells are well known to be the most important effector cells mediating antibody-dependent cellular cytotoxicity (ADCC) which is an important mechanism of action of antibody drugs. We evaluated the effects of chemotherapy on the cell number and activity of NK cells from patients who received the vincristine-cyclophosphamide-doxorubicin-prednisone (VCAP), doxorubicin-ranimustine-prednisone (AMP), and vindesine-etoposide-carboplatin-prednisone (VECP) (mLSG15) or mLSG15-like (-L) regimen, which is one of the standard of cares for newly diagnosed adult T-cell leukemia-lymphoma (ATL), or the cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) or CHOP-L regimen which is another standard of care for ATL and peripheral T-cell lymphoma (PTCL).MethodsThe number of lymphocytes and NK cells, and NK cell activity, were assessed using flow cytometry and a (51)Cr release assay, respectively.ResultsA total of 26 patients with untreated ATL or PTCL were enrolled, and blood samples from 25 patients were evaluable. NK cell number in ATL decreased after mLSG15/-L treatment, and the degree of decrease in the NK cell number was more prominent just before VECP therapy (Day 15-17 of each cycle) than just before VCAP therapy (Day 1 of each cycle). The NK cell number in ATL after CHOP/-L treatment also decreased. Interestingly, the NK cell activity showed a tendency to increase after the treatment. NK cell number in PTCL did not decrease by CHOP/-L regimen, but the activity was slightly decreased after the treatment.ConclusionsThese results indicate that the effects of chemotherapeutic agents on NK cells vary according to the disease type and intensity of chemotherapy.
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Project description:Different models to investigate the prognosis of peripheral T cell lymphoma not otherwise specified (PTCL-NOS) have been developed by means of retrospective analyses. Here we report on a new model designed on data from the prospective T Cell Project. Twelve covariates collected by the T Cell Project were analysed and a new model (T cell score), based on four covariates (serum albumin, performance status, stage and absolute neutrophil count) that maintained their prognostic value in multiple Cox proportional hazards regression analysis was proposed. Among patients registered in the T Cell Project, 311 PTCL-NOS were retained for study. At a median follow-up of 46 months, the median overall survival (OS) and progression-free survival (PFS) was 20 and 10 months, respectively. Three groups were identified at low risk (LR, 48 patients, 15%, score 0), intermediate risk (IR, 189 patients, 61%, score 1-2), and high risk (HiR, 74 patients, 24%, score 3-4), having a 3-year OS of 76% [95% confidence interval 61-88], 43% [35-51], and 11% [4-21], respectively (P < 0·001). Comparing the performance of the T cell score on OS to that of each of the previously developed models, it emerged that the new score had the best discriminant power. The new T cell score, based on clinical variables, identifies a group with very unfavourable outcomes.
| S-EPMC6033106 | biostudies-literature
Project description:T-cell lymphomas are rare malignancies that are often found in older individuals. Here we present the case of a 63 year old female that presented with diffuse cervical, inguinal, and axillary lymphadenopathy with associated weight loss and night sweats. The patient underwent excisional lymph node biopsy which revealed a T-cell lymphoma with findings characteristic of peripheral T-cell lymphoma, not otherwise specified.
| S-EPMC7296317 | biostudies-literature