Acute GVHD prophylaxis plus ATLG after myeloablative allogeneic haemopoietic peripheral blood stem-cell transplantation from HLA-identical siblings in patients with acute myeloid leukaemia in remission : final results of quality of life and long-term outcome analysis of a phase 3 randomised study

Background We previously showed that human anti-T-lymphocyte globulin (ATLG) plus ciclosporin and methotrexate given to patients with acute leukaemia in remission, having allogeneic haemopoietic stem-cell transplantation with peripheral blood stem cells from an HLA-identical sibling donor after myeloablative conditioning, significantly reduced 2-year chronic graft-versus-host disease (cGVHD) incidence and severity, without increasing disease relapse and infections, and improves cGVHD-free and relapse-free survival (cGRFS). The aim of an extended follow-up study was the assessment of long-term outcomes, which are, in this context, scarcely reported in the literature. We report unpublished data on quality of life (QoL) from the original study and the results of a follow-up extension. Methods In the original open-label study, patients with acute myeloid and lymphoblastic leukaemia in first or subsequent remission, having sibling HLA-identical allogeneic peripheral blood stem-cell transplantation, were randomly assigned (1:1) to receive ATLG plus standard GVHD prophylaxis with ciclosporin and short-term methotrexate (ATLG group) or standard GVHD prophylaxis without ATLG (non-ATLG group). Conditioning regimens were cyclophosphamide 120 mg/kg with either total body irradiation (12 Gy) or busulfan (12 . 8 mg/kg intravenously or 16 mg/kg orally), with or without etoposide (30-60 mg/kg). Randomisation was stratified according to centre and disease risk. The primary endpoint was cumulative incidence of cGVHD at 2 years. The primary and secondary endpoints, excluding QoL, have been published. QoL, assessed using European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-HDC29 questionnaires, was an unpublished secondary endpoint, which we now report here. A follow-up extension was then done, with the primary endpoint cumulative incidence of cGVHD. Enrolment has been completed for both studies. Findings In the original study, from Dec 14, 2006, to Feb 2, 2012, 161 patients were enrolled and 155 were randomly assigned to either the ATLG group (n=83) or to the non-ATLG group (n=72). In the follow-up study, which started on Feb 7, 2017, and was completed on June 30, 2017, 61 patients were included in the ATLG group and 53 were included in the non-ATLG group. Global health status showed a more favourable time course in the ATLG group compared with the non-ATLG group (p=0 . 02; treatment by visit interaction). ATLG was descriptively superior to non-ATLG at 24 months for physical function (points estimate -14.8 [95% CI -26.4 to-3.1]; p= 0.014) and social function (-19.1 [-38.0 to -0.2]; p=0.047), gastrointestinal side-effects (8 . 8 [2.5-15.1]; p=0 . 008) and effect on family (13.5 [1.2-25.8]; p=0.032). Extended follow-up (median 5 . 9 years [IQR 1.7-7.9]) confirmed a lower 5-year cGVHD incidence (30.0% [95% CI 21.4-41.9] vs 69.1% [59.1-80.1]; analysis for entire follow-up, p Interpretation The addition of ATLG to standard GVHD prophylaxis improves the probability of surviving without disease relapse and cGVHD after myeloablative peripheral blood stem-cell transplantation from an HLA-identical sibling donor for patients with acute leukaemia in remission. Further additional benefits are better QoL and shorter immunosuppressive treatment compared with standard GVHD prophylaxis without ATLG. Therefore, in this setting, ATLG plus standard GVHD prophylaxis should be preferred over the standard GVHD prophylaxis alone. Copyright (C) 2019 Elsevier Ltd. All rights reserved.Peer reviewe

Rapporto Maghreb. Riforme economiche e competitività

Le relazioni economiche tra l'Europa e il Maghreb, le riforme economiche e il partenariato euromediterraneo, l'Italia e il Maghreb.- Indice #9- Premessa #13- Cap.I Le relazioni economiche tra l’Europa e il Maghreb #15- Cap.II Riforme economiche e competitività internazionale in Marocco e Tunisia #29- Cap.III Le riforme economiche algerine #45- Cap.IV L’integrazione economica regionale e l’Unione del Maghreb Arabo #53- Cap.V L’accelerazione delle riforme economiche e il partenariato euromediterraneo #61- Appendice L’Italia e il Maghreb #69- Riferimenti bibliografici #7

Successful HLA haploidentical myeloablative stem cell transplantation for aggressive hepatosplenic alpha/beta (αβ) T-cell lymphoma

Hepatosplenic T cell lymphoma (HSTCL) is a type of hematologic neoplasia with a poor prognosis and a high frequency of refractoriness to conventional chemotherapy. The results obtained by high dose chemotherapy followed by autologous stem cells transplantation seem to be a more effective option but still unsatisfactory. Also the role of allogeneic stem cell transplantation is still unclear, although the few cases reported on the literature would seem to show good results in overall survival rates. In this paper, we reported the patient׳s medical history affected by a αβ variant of hepatosplenic T cell successfully rescued with a haploidentical transplant

Graft-versus-lymphoma effect in relapsed peripheral T-cell non-Hodgkin's lymphomas after reduced-intensity conditioning followed by allogeneic transplantation of hematopoietic cells

Purpose: Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of malignancies characterized by a poor prognosis. We performed a pilot study to investigate the role of reduced-intensity conditioning (RIC) followed by allogeneic stem-cell transplantation in relapsed or refractory PTCLs. Patients and Methods: We have conducted a phase II trial on 17 patients receiving salvage chemotherapy followed by RIC and allogeneic transplantation of hematopoietic cells. The RIC regimen consisted of thiotepa, fludarabine, and cyclophosphamide. The acute graft-versus-host disease prophylaxis consisted of cyslosporine and short course methotrexate. Results: Patients had a median age of 41 years (range, 23 to 60 years). Two patients were primary chemorefractory, and 15 had relapsed disease; eight patients (47%) had a disease relapse after an autologous transplantation. After a median follow-up of 28 months from the day of study entry (range, 3 to 57 months), 14 of 17 patients were alive (12 in complete remission, one in partial remission, and one with stable disease), two died as a result of progressive disease, and one died as a result of sepsis concomitant to acute graft-versus-host disease. The estimated 3-year overall and progression-free survival rates were 81% (95% CI, 62% to 100%) and 64% (95% CI, 39% to 89%), respectively. The estimated probability of nonrelapse mortality at 2 years was 6% (95% CI, 1% to 17%). Donor lymphocyte infusions induced a response in two patients progressing after allografting. Conclusion: RIC followed by allogeneic stem-cell transplantation is feasible, has a low treatment-related mortality, and seems to be a promising salvage treatment for relapsed PTCL. These findings suggest that the existence of a graft-versus-T-cell lymphoma effect

Graft-Versus-Lymphoma Effect in Relapsed Peripheral T-Cell Non-Hodgkin's Lymphomas After Reduced-Intensity Conditioning Followed by Allogeneic Transplantation of Hematopoietic Cells.

RIC followed by allogeneic stem-cell transplantation is feasible, has a low treatment-related mortality, and seems to be a promising salvage treatment for relapsed PTCL. These findings suggest that the existence of a graft-versus-T-cell lymphoma effec