Impact of in vivo T-cell depletion on outcome of AML patients in first CR given peripheral blood stem cells and reduced-intensity conditioning allo-SCT from a HLA-identical sibling donor: a report from the Acute Leukemia Working Party of the European group for Blood and Marrow Transplantation

Abstract

The impact of in vivo T-cell depletion on transplantation outcomes in patients transplanted with reduced-intensity conditioning (RIC) remains controversial. This study assessed the outcome of 1250 adult patients with de novo AML in first CR (CR1) given PBSC from HLA-identical siblings after chemotherapy-based RIC. A total of 554 patients did not receive any form of in vivo T-cell depletion (control group), whereas antithymocyte globulin (ATG) and alemtuzumab were given in 444 and 252 patients, respectively. The incidences of grade II-IV acute GVHD were 21.4, 17.6 and 10.2% in control, ATG and alemtuzumab patients, respectively (Po0.001).In multivariate analysis, the use of ATG and the use of alemtuzumab were each associated with a lower risk of chronic GVHD (Po0.001 each), but a similar risk of relapse, and of nonrelapse mortality, and similar leukemia-free survival and OS. Further, among patients given BU-based RIC, the use of o6 mg/kg ATG did not increase the risk of relapse (hazard ratio, HR ¼ 1.1), whereas there was a suggestion for higher relapse risk in patients given X6 mg/kg ATG (HR ¼ 1.4, P ¼ 0.08). In summary, these data suggest that a certain amount of in vivo T-cell depletion can be safely used in the conditioning of AML patients in CR1 given PBSC after chemotherapy-based RIC. INTRODUCTIONThe use of PBSC instead of BM in patients receiving grafts from HLA-matched donors after myeloablative conditioning has been associated with faster hematological recovery, lower relapse risk in patients with advanced disease (due to higher immune-mediated graft-versus-tumor (GVT) effects), but also higher incidence extensive chronic GVHD. 1-4 These observations prompted several groups of investigators to study in vivo T-cell depletion of the graft with antithymocyte globulin (ATG) or alemtuzumab as a way to reduce severe GVHD in patients given PBSC after highdose myeloablative conditioning regimen. [5][6][7] These studies demonstrated that the use of ATG or alemtuzumab was successful at preventing severe GVHD without apparently increasing the relapse incidence (RI). [5][6][7] In contrast to patients given grafts after myeloablative conditioning who benefit from both the high-dose chemo/radiotherapy given as part of the conditioning regimen and the GVT effect for tumor eradication,

Outcome of conditioning intensity in acute myeloid leukemia with monosomal karyotype in patients over 45 year‐old: A study from the acute leukemia working party (ALWP) of the European group of blood and marrow transplantation (EBMT)

“…Other retrospective studies comparing RIC with MAC in AML have shown similar DFS and OS as in our analysis, but the increased relapse incidence usually associated with RIC was not found in the present report [16,30]. We also found that in-vivo T-cell depletion with ATG was not associated with an increased risk of relapse as it has been recently described [31].…”

The impact of graft-versus-host disease prophylaxis in reduced-intensity conditioning allogeneic stem cell transplant in acute myeloid leukemia: a study from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

“…11 In contrast, a similar recent EBMT study failed to detect either association. 12 Because transplant outcomes are also dependent on recipient age, type of donor, disease risk and status at transplant, 22,23 in order to evaluate the impact of GVHD prophylaxis on transplant outcomes more accurately, in the present study we limited the analysis to a very homo-GVHD prophylaxis in RIC HSCT haematologica | 2015; 100 (5) 687 Table 3. Transplant outcomes at 2 years after allogeneic hematopoietic stem cell transplantation according to the GVHD prophylaxis.…”

“…The impact of graft-versus-host disease prophylaxis in reduced-intensity conditioning allogeneic stem cell transplant in acute myeloid leukemia: a study from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation Marie Thérèse Rubio, 1,2,3 Myriam Labopin, 1,4 Didier Blaise, 5 Gerard Socié, 6 Rafael Rojas Contreras, 7 Patrice Chevallier, 8 Miguel A. Sanz, 9 Stéphane Vigouroux, 10 Anne Huynh, 11 Avichai Shimoni, 12 Claude-Eric Bulabois, 13 Nerea Caminos, 14 Lucía López-Corral, 15 Arnon Nagler, 12,4 * and Mohamad Mohty 1,2,3,4 * been poorly explored. While, the combination of CsA and a short course of methotrexate (MTX) after transplantation is considered as the gold standard for GVHD prophylaxis after conventional myeloablative allogeneic HSCT from HLA-identical siblings, 15,16 there is no consensus on the optimal preventive regimen for GVHD prophylaxis after RIC allogeneic HSCT.…”

“…3,11 It is now established that the effects of ATG in RIC are dose-dependent, 3 and that intermediate doses of thymoglobulin between 4 and 6 mg/kg seem to prevent GVHD optimally while sparing the GVL effect. [12][13][14] Apart from ATG, the impact of the post-transplant immunosuppression on transplant outcomes in allogeneic HSCT following RIC has October 19, 2014. Manuscript accepted March 6, 2015.…”

In patients older than 55 years with AML in first CR, should we search for a matched unrelated donor when an old sibling donor is available?

“…However, our results are in accordance with earlier report by other smaller studies, [21][22][23] as well as to a recent publication by our group on 1250 adult patients with de novo AML in CR1 given PBSC from HLA-identical siblings after chemotherapy-based RIC regimen, where the use of ATG and the use of alemtuzumab were each associated with a lower risk of chronic GVHD, but a similar risk of relapse. 24 Because of the selection criteria (only patients 8/8 matched were considered), we were unable to assess the impact of mismatches on the risk of chronic GvHD and eventually NRM. Moreover, the type and dose of ATG were unknown for a sizeable number of the patients in our study.…”