Tandem versus single haematopoietic stem cell transplant and BV maintenance in relapsed/refractory Hodgkin lymphoma: A matched cohort analysis from the LYSA.

Autologous hematopoietic stem cell transplant (ASCT) is the standard curative treatment for patients with high-risk relapsed/refractory Hodgkin lymphoma (R/R HL). The AETHERA study showed survival gain with Brentuximab Vedotin (BV) maintenance after ASCT in BV-naive patients, which was recently confirmed in the retrospective AMAHRELIS cohort, including a majority of BV-exposed patients. However, this approach has not been compared to intensive tandem auto/auto or auto/allo transplant strategies, which were used before BV approval. Here, we matched BV maintenance (AMAHRELIS) and tandem SCT (HR2009) cohorts, and observed that BV maintenance was associated with better survival outcome in patients with HR R/R HL.

[Retrospective cohort study of rituximab biosimilar (Rixathon®) adverse events in adult hematology and pediatric nephrology]. / Etude de cohorte rétrospective sur les effets indésirables du biosimilaire du rituximab (Rixathon®) en hématologie adulte et néphrologie pédiatrique.

The purpose of this study was to describe rituximab biosimilar safety in adult hematology and pediatric nephrology units. Adverse events were classified using the Common Terminology Criteria for Adverse Events (CTCAE) classification. Fifty adult patients were enrolled for a total of 126 cures and 11 pediatric patients for a total of 24 biosimilar cures. Among adults, three infusion-related reactions of biosimilar occurred : a bronchospasm, a reaction at the injection site and emesis. Among children, infusion-related reactions were: a bronchospasm, an injection site reaction, an emesis, and diarrhea. For adults, the most common adverse events included neutropenia (13.5 %) with 9 severe grade 3/4 cases, anemia (8.7 %), grade 1 thrombocytopenia (6.3 %), asthenia (2.4 %), infection (2.4 %), and chills (1.6 %). For children, a case of severe grade 4 neutropenia, a fever and conjunctivitis were observed. Results of this study show a confident safety profile of rituximab biosimilar in adults and children in «real life¼.

L'objectif de ce travail est de décrire les effets indésirables du biosimilaire du rituximab en «vie réelle¼ dans les services d'Hématologie adulte et de Néphrologie pédiatrique. Les effets indésirables ont été codés selon la classification des «Common Terminology Criteria for Adverse Events¼ (CTCAE). Cinquante patients adultes ont été inclus pour un total de 126 cures et 11 enfants pour un total de 24 cures de biosimilaire. Chez l'adulte, des réactions liées à la perfusion du biosimilaire ont été caractérisées par un bronchospasme avec frissons, une réaction au point d'injection et un cas de vomissements. Chez les enfants, les réactions liées à la perfusion étaient similaires avec un bronchospasme, une réaction au point d'injection, un cas de vomissements, et un cas de selles liquides. Chez les adultes, les effets indésirables les plus fréquents étaient la neutropénie (13,5 %), une anémie (8,7 %), une thrombopénie de grade 1 (6,3 %), une asthénie (2,4 %), une infection (2,4 %). Chez les enfants, un cas de neutropénie de grade 4, une fièvre et une conjonctivite ont été enregistrés. Le profil d'effets indésirables du biosimilaire du rituximab chez les adultes et les enfants est rassurant.

Enteropathy-associated T-cell lymphoma: improving treatment strategies.

Enteropathy-associated T-cell lymphoma (EATL) is a rare and usually rapidly fatal intestinal T-cell non-Hodgkin lymphoma. It arises from intraepithelial lymphocytes and has a high association with coeliac disease. The high mortality of EATL is associated not only with the very aggressive and often chemotherapy-refractory nature of the lymphoma. The poor condition of patients due to prolonged and severe malnutrition compromises the ability to deliver chemotherapy. There are no standardized treatment protocols, and the optimal therapy for EATL remains unclear. The primary step of treatment consists of local debulking, preferably as early as possible after EATL diagnosis. Morbidity and mortality seem to rise with advanced stages of disease due to tumour size progression, worse nutritional status and a higher risk of emergency surgery due to perforation. Standard induction therapy for EATL is anthracycline-based chemotherapy, preferably resumed between 2 and 5 weeks after surgery (depending on clinical condition). Intensification of therapy using high-dose chemotherapy followed by consolidation with BEAM and autologous stem cell transplantation is associated with better outcome. Notably, this treatment strategy has only been applied in patients eligible for this aggressive regimen which might reflect selection bias. Unfortunately, prognosis of EATL remains poor; 5-year survival varies from 8 to 60% depending on the eligibility to receive additional steps of therapy. New treatment strategies are urgently needed for a better prognosis of this lethal complication of coeliac disease. Brentuximab vedotin (anti-CD30) might be promising when added to conventional chemotherapy and is suggested as upfront treatment in EATL.

Identification of prognostic factors predicting outcome in Hodgkin's lymphoma patients relapsing after autologous stem cell transplantation.

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed Hodgkin's lymphoma (HL). However, there is currently little information on the predictors of outcome for patients whose disease recurs after ASCT. METHODS: Five hundred and eleven adult patients with relapsed HL after ASCT from EBMT-GITMO databases were reviewed. RESULTS: Treatments administered following ASCT failure included conventional chemotherapy and/or radiotherapy in 294 (64%) patients, second ASCT in 35 (8%), and alloSCT in 133 (29%). After a median follow-up of 49 months, overall survival (OS) was 32% at 5 years. Independent risk factors for OS were early relapse (<6 months) after ASCT, stage IV, bulky disease, poor performance status (PS), and age ≥50 years at relapse. For patients with no risk factors OS at 5 years was 62% compared with 37% and 12% for those having 1 and ≥2 factors, respectively. This score was also predictive for outcome in each group of rescue treatment after ASCT failure. CONCLUSION(S): Early relapse, stage IV, bulky disease, poor PS, and age ≥50 years at ASCT failure are relevant factors for outcome that may help to understand the results of different therapeutic approaches.

Two atypical cases of cutaneous gamma/delta T-cell lymphomas.

Cutaneous γ/δ T-cell lymphoma (CGD-TCL) is a recent entity described in the newly revised World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas, and is characterized by the γ/δ T-cell receptor expression on atypical lymphocytes. Only a few cases of primary CGD-TCL have been reported, with an extremely aggressive course (median survival time of 15 months). We describe 2 atypical cases of CGD-TCL. The first case was initially misdiagnosed as an inflammatory panniculitis due to the granulomatous infiltrate on the skin biopsy specimen. Diagnosis was confirmed using δ PCR that revealed γ/δ T-cell clonal expansion. The evolution was marked by predominant γ/δ T-cell infiltrate with diffuse body fat involvement as seen on positron emission tomography-computed tomography. The second case is the first described Epstein-Barr virus (EBV)-associated CGD-TCL with a rapidly fatal evolution. CGD-TCL is also a heterogeneous entity and δ PCR and EBV-encoded RNA probe to detect an EBV latent infection may help diagnose and characterize these cutaneous lymphomas.

Analysis of factors influencing inclusion of 102 patients with stage III/IV Hodgkin's lymphoma in a randomized trial for first-line chemotherapy.

BACKGROUND: Data on factors influencing inclusion of Hodgkin's lymphoma (HL) patients in randomized clinical trials (RCT) are limited and, for the present study they were analyzed in a RCT for III/IV HL. PATIENTS AND METHODS: All patients with stage III/IV HL referred to the Saint-Louis Hospital between January 2003 and May 2007 were studied. A Groupe d'Etudes des Lymphomes de l'Adulte/European Organisation for Research and Treatment of Cancer RCT, to compare ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) with increased-dose BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone), was open for recruitment. Noninclusion criteria and physician's reasons for non-recruitment were prospectively recorded. The reasons for patient's refusal were collected retrospectively. Logistic regression analyses were carried out in order to identify factors predicting inclusion. RESULTS: A total of 102 patients were diagnosed, among whom 51% were included. Seven patients were ineligible, 22 refused to participate, and 21 were not enrolled due to the physician's decision. Main reasons for patients' refusal were standard treatment preference and concerns about experimental arm toxicity, mainly infertility risk. Conditions that could hamper accurate follow-up and toxicity concerns accounted for most of the physicians' reasons. Adverse prognostic factors [B symptoms (odds ratio, OR = 5.35) and international prognostic score > or =3 (OR = 2.69)] were independently associated with inclusion. CONCLUSION: Despite an attractive protocol, only 51% of patients were included. It highlights concerns about selection of patients and the difficulty to obtain informed consent with better prognostic profile patients.

Pre-transplant donor CD4- invariant NKT cell expansion capacity predicts the occurrence of acute graft-versus-host disease.

Clinically useful pre-transplant predictive factors of acute graft-versus-host-disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT) are lacking. We prospectively analyzed HSC graft content in CD34+, NK, conventional T, regulatory T and invariant natural killer T (iNKT) cells in 117 adult patients before allo-SCT. Results were correlated with occurrence of aGVHD and relapse. In univariate analysis, iNKT cells were the only graft cell populations associated with occurrence of aGVHD. In multivariate analysis, CD4- iNKT/T cell frequency could predict grade II-IV aGVHD in bone marrow and peripheral blood stem cell (PBSC) grafts, while CD4- iNKT expansion capacity was predictive in PBSC grafts. Receiver operating characteristic analyses determined the CD4- iNKT expansion factor as the best predictive factor of aGVHD. Incidence of grade II-IV aGVHD was reduced in patients receiving a graft with an expansion factor above versus below 6.83 (9.7 vs 80%, P<0.0001), while relapse incidence at two years was similar (P=0.5).The test reached 94% sensitivity and 100% specificity in the subgroup of patients transplanted with human leukocyte antigen 10/10 PBSCs without active disease. Analysis of this CD4- iNKT expansion capacity test may represent the first diagnostic tool allowing selection of the best donor to avoid severe aGVHD with preserved graft-versus-leukemia effect after peripheral blood allo-SCT.

Autologous hematopoietic stem cell transplantation in elderly patients (≥ 70 years) with non-Hodgkin's lymphoma: A French Society of Bone Marrow Transplantation and Cellular Therapy retrospective study.

INTRODUCTION: Limited data is available on the feasibility of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) in elderly patients over 70 years of age with non-Hodgkin's lymphoma (NHL). MATERIALS AND METHODS: In the setting of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) group, we retrospectively analyzed 81 consecutive patients with NHL over 70 years of age who received AHSCT. RESULTS: The median age at AHSCT was 72.3 years [70-80]. Patients' were diagnosed with diffuse large B-cell lymphoma (n=40), follicular lymphoma (n=16), mantle cell lymphoma (n=15), T-cell lymphoma (n=5), and other (n=5). Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) was 0 in 73% of patients. Main conditionings were BEAM (Carmustine-Etoposide-Cytarabine-Melphalan, n=61) and melphalan alone (n=14). Median delays to reach 0.5×109/L neutrophils and 20 × 10(9)/L platelets were of 12 [9-76] days and 12 [0-143] days, respectively. One hundred day and one year cumulative incidence of NRM was 5.4% and 8.5%, respectively. The main cause of death remains relapse. CONCLUSION: In conclusion, this study revealed that AHSCT seemed to be acceptable in patients over 70 years of age with NHL. Patient age is not a limiting factor if clinical condition is adequate.