Antithymocyte Globulin in Reduced-Intensity Conditioning Regimen Allows a High Disease-Free Survival Exempt of Long-Term Chronic Graft-versus-Host Disease

AbstractNonmyeloablative (NMA) regimens allow the use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients considered unfit for standard myeloablative conditioning (MAC) regimens using high-dose alkylating agents with or without total body irradiation (TBI). Reduced-intensity conditioning (RIC) regimens, based on fludarabine (Flu), busulfan (Bu), and rabbit antithymocyte globulin (r-ATG), represent an intermediate alternative between NMA and MAC regimens. This platform was subsequently optimized by the introduction of i.v. Bu and the use of 5 mg/kg r-ATG, based on the hypothesis that these modifications would improve the safety of RIC allo-HSCT. Here we report a study conducted at our institution on 206 patients, median age 59 years, who underwent allo-HSCT after conditioning with Flu, 2 days of i.v. Bu, and 5 mg/kg r-ATG (FBx-ATG) between 2005 and 2012. The prevalence of grade III-IV acute graft-versus-host disease (GVHD) was 9%, and that of extensive chronic GVHD was 22%. Four-year nonrelapse mortality (NRM), relapse, and overall survival (OS) rates were 22%, 36%, and 54%, respectively. NRM tended to be influenced by comorbidities (hematopoietic cell transplantation–specific comorbidity index [HCT-CI] <3 versus HCT-CI ≥3: 18% versus 27%; P = .075), but not by age (<60 years, 20% versus ≥60 years, 25%; P = .142). Disease risk significantly influenced relapse (2 years: low, 8%, intermediate, 28%, high, 34%; very high, 63%; P = .017). Both disease risk (hazard ratio [95% confidence interval]: intermediate, 2.1 [0.8 to 5.2], P = .127; high, 3.4 [1.3 to 9.1], P = .013; very high, 4.0 [1.1 to 14], P = .029) and HCT-CI (hazard ratio [95% confidence interval]: HCT-CI ≥3, 1.7 (1.1 to 2.8), P = .018) influenced OS, but age and donor type did not. The FBx-ATG RIC regimen reported here is associated with low mortality and high long-term disease-free survival without persistent GVHD in both young and old patients. It represents a valuable platform for developing further post-transplantation strategies aimed at reducing the incidence of relapse, particularly in the setting of high-risk disease

Peripheral Blood Stem Cells versus Bone Marrow for T Cell-Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide in Hodgkin Lymphoma.

Abstract Haploidentical stem cell transplantation (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) represents a potential curative strategy for patients with Hodgkin lymphoma (HL) when a matched related or unrelated donor is not available. The role of graft source, either bone marrow (BM) or peripheral blood stem cells (PBSCs), in this setting has not been fully elucidated. We performed a retrospective study on 91 patients with HL to compare the outcome after BM (n = 53) or PBSC (n = 38) transplant. Eighty-nine patients engrafted with no difference between BM and PBSCs in terms of median time for neutrophil (20 versus 20 days, P = .405) and platelet (26 versus 26.5 days, P = .994) engraftment. With a median follow-up of 40.2 months, 100-day cumulative incidences of grades II to IV acute graft-versus host disease (GVHD) and grades II to IV acute GVHD were 24% and 4%, respectively. Graft source was not associated with a different risk of acute GVHD both by univariate and multivariate analyses. Consistently, 1-year cumulative incidence of chronic GVHD was 7% with no differences between the 2 graft types (P = .761). Two-year rates of overall survival (OS), progression-free survival (PFS), nonrelapse mortality, and GVHD/relapse-free survival (GRFS) were 67%, 58%, 20%, and 52%, respectively. By univariate analysis, pretransplant disease status was the main variable affecting all outcomes. By multivariate analysis, PBSCs resulted in a protective factor for OS (hazard ratio [HR], .29; P = .006), PFS (HR, .38; P = .001), and GRFS (HR, .44; P = .020). The other independent variables affecting the final outcome were pretransplant disease status and hematopoietic cell transplant–specific comorbidity index. In conclusion, when planning a haplo-SCT with PT-Cy for patients with poor-risk HL, graft type is an important variable to take into account when selecting the best available donor

Open Questions in the Management of Nodular Lymphocyte Predominant Hodgkin Lymphoma

Localized Nodular Lymphocyte Predominant Hodgkin Lymphoma is a rare disease with an overall good prognosis but frequent late relapses. Due to it’s rarity there is no standard therapeutic approach and pathological diagnosis may be hard. In this paper we discuss the technical aspects of the radiation therapy and histological issues. The new fields reductions proposed for classical Hodgkin lymphoma cannot be applied to early stages Nodular Lymphocyte Predominant Hodgkin lymphomas which are usually treated with radiation therapy without systemic chemotherapy

Co-occurrence of mucosal leishmaniasis caused by Leishmania infantum and mucosal-associated lymphoid tissue lymphoma

International audienc

Impact of post-brentuximab vedotin consolidation on relapsed/refractory CD30+ Hodgkin lymphomas: a large retrospective study on 240 patients enrolled in the French Named-Patient Program

International audienceBrentuximab vedotin was reported to be effective and safe against refractory/relapsed Hodgkin lymphoma in cohorts of 12 to 102 patients. Herein we report our retrospective analysis of the French experience with brentuximab vedotin used alone to treat 240 refractory/relapsed Hodgkin lymphoma patients enrolled in a named patient program between 2011 and 2013. All patients had histologically documented CD30+ Hodgkin lymphoma; 74% had refractory disease or early relapses. After a median of 3 chemotherapy lines, brentuximab vedotin was infused intravenously (1.8 mg/kg every 3 weeks). The primary endpoint was best response. Response at the end of treatment, its duration, survival data and toxicity profile were secondary endpoints. Patients received a median of 6 cycles; 68 underwent a consolidation thereafter. The best response was observed after a median of 4 cycles in 145 (60.4%) patients: 33.8% complete response/unconfirmed complete response, 26.7% partial response. Objective responses were observed decreased (39.3%) in the 28 patients \textgreater60 years. Median response duration was 8.4 months. With median follow-up at 16.1 months, median progression free-survival was 6.8 months and significantly longer for patients transplanted after brentuximab vedotin (median at 18,8 months); median overall survival was not reached. No death has been linked to brentuximab vedotin toxicity. The most common adverse events were peripheral sensory neuropathy (29.3%) and hematological toxicity. The results of this analysis support the previously reported brentuximab vedotin efficacy with manageable toxicity. Because short-term responses in most patients, high-dose therapy with stem-cell transplantation for responders should be considered rapidl

Obinutuzumab (GA101) Monotherapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma or Mantle-Cell Lymphoma: Results From the Phase II GAUGUIN Study

International audiencePurposeObinutuzumab (GA101), a type II, glycoengineered, humanized anti-CD20 monoclonal antibody, was superior to rituximab in human diffuse large B-cell lymphoma (DLBCL) and mantle-cell lymphoma (MCL) xenograft models. In phase I of our study, obinutuzumab (GA101) exhibited encouraging activity but no clear dose-response relationship, and few patients had aggressive histologies. The efficacy and safety of two doses of obinutuzumab (GA101) were explored in our randomized phase II trial in patients with heavily pretreated DBLCL and MCL.Patients and MethodsPatients were randomly assigned to receive eight cycles of obinutuzumab (GA101) either as a flat dose of 400 mg for all infusions (days 1 and 8 of cycle 1; day 1 of cycles 2 to 8) or 1,600 mg on days 1 and 8 of cycle 1 and 800 mg on day 1 of cycles 2 to 8.ResultsForty patients were enrolled: 21 patients in the 400/400-mg treatment arm (DLBCL, n = 10; MCL, n = 11) and 19 patients in the 1,600/800-mg arm (DLBCL, n = 15; MCL, n = 4). End-of-treatment response was 28% (32% and 24% in the 1,600/800-mg and 400/400-mg study arms, respectively). Best overall response rates were 37% in the 1,600/800-mg arm and 24% in the 400/400-mg study arm (DLBCL, eight [32%] of 25 patients; MCL, four [27%] of 15 patients). Five (20%) of 25 rituximab-refractory patients exhibited treatment response, including four of 12 in the 1,600/800-mg group. The most common adverse events were infusion-related reactions (IRRs), which were manageable. Three patients had grade 3/4 IRRs. Grade 3/4 neutropenia was seen in only one patient.ConclusionObinutuzumab (GA101) 1,600/800 mg achieves early steady-state concentration and clinical activity with an acceptable safety profile in relapsed/refractory DLBCL and MCL, supporting further exploration

Ovarian function recovery in newly diagnosed advanced Hodgkin lymphoma patients treated with PET-adapted regimen: Prospective analysis of a multicentric randomized phase 3 trial (AHL2011).

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