Outcomes of hematopoietic stem cell transplantation from unmanipulated haploidentical versus matched sibling donor in patients with acute myeloid leukemia in first complete remission with intermediate or high-risk cytogenetics: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Abstract

Allogeneic hematopoietic stem cell transplantation is the optimal care for patients with high-risk or intermediate - acute myeloid leukemia. In patients lacking matched sibling donor, haploidentical donors are an option. We compared outcomes of unmanipulated (Haplo) to matched sibling donor transplant in acute myeloid leukemia patients in first complete remission. Included were intermediate and high-risk acute myeloid leukemia in first complete remission undergoing Haplo and matched sibling donor transplant from 2007–2015, and reported to the ALWP of the EBMT. A propensity score technique was used to confirm results of main analysis: 2 matched sibling donors were matched with 1 Haplo. We identified 2654 pts (Haplo =185; matched sibling donor =2469), 2010 with intermediate acute myeloid leukemia (Haplo=122; matched sibling donor =1888) and 644 with high-risk acute myeloid leukemia (Haplo =63; matched sibling donor =581). Median follow up was 30 (range 1–116) months. In multivariate analysis, in intermediate - acute myeloid leukemia patients, Haplo resulted in lower leukemia-free survival (Hazard Ratio 1.74; P<0.01), overall-survival (HR 1.80; P<0.01) and GvHD-free-relapse-free survival (Hazard Ratio 1.32; P<0.05) and higher graft-versus-host disease (GvHD) non-relapse mortality (Hazard Ratio 3.03; P<0.01) as compared to matched sibling donor. In high-risk acute myeloid leukemia, no differences were found in leukemia-free survival, overall-survival, and GvHD-free- relapse-free survival according to donor type. Higher grade II-IV acute GvHD was observed for Haplo in both high-risk (Hazard Ratio 2.20; P<0.01) and intermediate risk (Hazard Ratio 1.84; P<0.01). A trend for a lower Relapse-Incidence was observed in Haplo among high-risk acute myeloid leukemia (Hazard Ratio 0.56; P=0.06). The propensity score analysis confirmed results. Our results underline that matched sibling donor is the first choice for acute myeloid leukemia patients in first complete remission. On the other hand, results of Haplo transplants are similar to matched sibling donor transplants in acute myeloid leukemia patients with high risk cytogenetics.

Stem cell transplantation from a haploidentical donor versus a genoidentical sister for adult male patients with acute myelogenous leukemia in first remission: A retrospective study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation

“…For many teams, HAPLO donors are becoming the first choice when an alternative donor is sought. The question whether a HAPLO donor might produce outcomes similar to those produced by genoidentical donors has recently been investigated retrospectively by the EBMT in a matched‐pair analysis of 2654 adult patients with intermediate‐risk and high‐risk leukemia . In a multivariate analysis of patients with intermediate‐risk disease, the use of MSDs was associated with higher LFS, OS, and GRFS and with lower GVHD‐related NRM.…”

“…The more recent study from the EBMT of patients who underwent transplantation from 2007 to 2015 compared MSDs with HAPLO donors in recipients who had AML in CR1. That group reported similar outcomes in patients with adverse‐risk cytogenetics.…”

“…In view of the predicted higher NRM and lower LFS and OS associated with the female‐to‐male transplantation combination, one might question whether HAPLO transplantation would result in a similar or even better outcome. Indeed, for patients with high‐risk AML, there are indications that the relapse incidence (RI) may be lower with a HAPLO donor than with an MSD …”

Is a matched sibling the ideal donor for hematopoietic cell transplant?

“…In the group with patients aged 18-54 years, a comparison of haploidentical to HLA-matched sibling transplant did not reveal differences in survival. The characteristics of the patients studied in two reports and their numbers differ 1,2 and this is the most likely explanation for the differences between the two reports. As the report by Salvatore and colleagues did not consider donor-recipient relationship, we do not know whether the effect of cytogenetic risk on survival may be explained by donor-recipient relationship and patient age on survival.…”

“…1 They conclude survival was inferior after transplantation of peripheral blood or bone marrow from a haploidentical relative compared to an HLA-matched sibling for patients with intermediate-risk cytogenetics. On the other hand, for patients with high-risk cytogenetics, survival did not differ by donor type despite a non-significant reduction in relapse risk after haploidentical transplant.…”