Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission

Abstract

HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy–based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor–based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P = .15), leukemia-free survival (P = .50), nonrelapse mortality (P = .16), relapse (P = .90), or grade II-IV acute GVHD (P = .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P < .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease–donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy–based Haplo-HCT vs MSD using calcineurin inhibitor–based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients.

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

“…In a CIBMTR retrospective study in patients who underwent transplantation for AML in CR1, 336 who underwent a PTCY‐based HAPLO transplantation were compared with 869 who underwent an MSD transplantation using calcineurin GVHD prevention. The HAPLO group had a significantly lower incidence of cGVHD but had similar other outcomes, leading to the conclusion that a HAPLO transplantation with PTCY was a viable alternative to MSD transplantation in this patient population . Finally, in a recent joint EBMT‐CIBMTR study, patient age appeared to be important, with equivalent outcomes reported using MSDs or HAPLO donors in patients aged <55 years, but with better outcomes using MSDs in older patients …”

“…The HAPLO group had a significantly lower incidence of cGVHD but had similar other outcomes, leading to the conclusion that a HAPLO transplantation with PTCY was a viable alternative to MSD transplantation in this patient population. 4 Finally, in a recent joint EBMT-CIBMTR study, patient age appeared to be important, with equivalent outcomes reported using MSDs or HAPLO donors in patients aged <55 years, but with better outcomes using MSDs in older patients. 46 In view of these results, we considered a practical possible clinical issue: ie, what would be the best choice for transplantation in a male patient with intermediate-risk or high-risk AML who has a unique genoidentical sister available.…”

“…The CIBMTR study, which compared outcomes between 869 patients with AML in CR1 who underwent transplantation from an MSD and 336 patients who underwent PTCY HAPLO transplantation, had similar outcomes. However, that study did not addressed the question we raised in our own study; ie, male recipients receiving sister MSD versus HAPLO transplantation stratified by cytogenetics.…”

T-Cell Immunotherapies Targeting Histocompatibility and Tumor Antigens in Hematological Malignancies

“…In both cases, the risk of GVHD (especially chronic GVHD) is surprising low. Although the reasons for this are incompletely understood, several factors, such as the intensity of the immunosuppression in haplo-identical AHCT, or the intrinsic features of the graft in terms of cell composition and functionality in cord blood transplants, may contribute to this observation (29,30). Moreover, in certain circumstances, the risk of relapse appears to be lower following these mismatched transplants, arguing in favor of enhanced GVT in these settings (31)(32)(33).…”

ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia

“…Nonetheless, the timely availability of a matched unrelated donor (MUD), high incidences of chronic GvHD (cGvHD), and high relapse rates remain well-known obstacles to the overall improvement of outcome after allogeneic HSCT [2,3]. As most patients have multiple potential haploidentical family donors, recent advances in both T-cell-replete and T-celldepleted haploidentical HSCT have overcome donor shortage and are now challenging the standard use of matched HSCT without compromising outcomes [4][5][6][7][8][9][10][11][12][13][14]. In vivo depletion of alloreactive T cells with posttransplant cyclophosphamide (PTCY) is the most frequently utilized approach to haploidentical HSCT, yet severe GvHD still occurs despite use of immunosuppression and relapse remains an ongoing concern [15][16][17][18][19].…”