Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation

Abstract

Because information on management and outcome of AML relapse after allogeneic hematopoietic stem cell transplantation (HSCT) with reduced intensity conditioning (RIC) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of EBMT. Among 2815 RIC transplants performed for AML in complete remission (CR) between 1999 and 2008, cumulative incidence of relapse was 32% ؎ 1%. Relapsed patients (263) were included into a detailed analysis of risk factors for overall survival (OS) and building of a prognostic score. CR was reinduced in 32%; remission duration after transplantation was the only prognostic factor for response (P ‫؍‬ .003).

Azacitidine salvage therapy for relapse of myeloid malignancies following allogeneic hematopoietic SCT

“…However, disease relapse following allo-HSCT remains challenging 21 and current attempts to treat these patients are still disappointing. Retrospective analyses of AZA given at various doses and schedules for post-transplant relapse of AML and/or MDS have reported a response rate ranging from 55 to 72%, but with a poor survival ranging from 16 to 23% at 2 years.…”

Comparison of Intensive Chemotherapy and Hypomethylating Agents before Allogeneic Stem Cell Transplantation for Advanced Myelodysplastic Syndromes: A Study of the Myelodysplastic Syndrome Subcommittee of the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplant Research

“…Although small numbers meant the poor and very poor groups had to be combined for analysis, we demonstrate a significant adverse effect of adverse cytoge-netics on relapse and RFS, underlying the importance of considering the pretransplantation karyotype on prognosis. The relapse incidence of 61% at 3 years in these patients, along with currently re ported poor outcomes in those who relapse after transplantation [15,16], indicates the urgent need for strategies directed at prevention of post-HSCT relapse.…”

Cytokine Release Patterns in Mixed Lymphocyte Culture (MLC) of T-Cells with Dendritic Cells (DC) Generated from AML Blasts Contribute to Predict anti-Leukaemic T-Cell Reactions and Patients’ Response to Immunotherapy

“…DLIs can be applied therapeutically for treatment of relapse after SCT or prophylactically in order to stabilize remissions -indicating again the central role of T-cells (Roddie et al 2006;Barrett & Savani 2006;Schmid et al 2007). For an improvement of therapy of AML-/MDS-pts at relapse after SCT GM-CSF might be applied in the context of DLI in order to facilitate the generation of APC from leukaemic blasts and thereby to increase antileukaemic activities of donor T-cells against myeloid blasts, as already shown by others and us in ex vivo settings (Kufner et al 2005;Kremser et al 2010;Schmid et al 2011;Dreyßig et al 2011). We could already show that compared to 'MNC'-stimulation stimulation of T-cells with 'DC'/DC leu , as effective APCs presenting the complete leukaemic antigenic repertoire, gives rise to a better mediation of an antileukaemic T-cell response in vitro thereby potentially contributing to a better response to DLI after allogeneic SCT in vivo (Kufner et al 2005;Kremser et al 2010;Grabrucker et al 2010;Dreyßig et al 2011;Buhmann et al 2016).…”

“…However, graft-versus-host reactions (GVH) of donor T-cells directed against host tissue (e.g. HLA-) antigens can jeopardize the efficiency of SCT or relapse therapy (Kolb et al 1995;Schmid et al 2006;Ferrara et al 2009;Schmid et al 2011;Schmetzer & Schmid 2012). Since cytokines, interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor-necrosis-factor-a (TNF-a) and interferon-c (IFN-c) in particular, are a main part of the pathophysiology of GVHD, they can be monitored and/or used to develop therapeutic strategies (Ferrara et al 2009).…”

“…After reduced intensity SCT in AML in CR, relapse rates between 20% and 55% have been reported, being significantly higher than those observed after myeloablative conditioning . Therapeutic donor lymphocyte infusions (DLI) applied in relapsed patients (pts) after SCT demonstrate the pivotal role of donor T-cells in anti-leukaemic reactions (Kolb et al 1995;Schmid et al 2006;Schmid et al 2011;Schmetzer & Schmid 2012). However, graft-versus-host reactions (GVH) of donor T-cells directed against host tissue (e.g.…”