Comparison of Outcomes after Unrelated Double-Unit Cord Blood and Haploidentical Peripheral Blood Stem Cell Transplantation in Adults with Acute Myelogenous Leukemia: A Study on Behalf of Eurocord and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Unmanipulated haploidentical hematopoietic stem cell transplantation (HCT) with post-transplantation cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis (haplo-PTCY) and unrelated double-unit umbilical cord blood transplantation (dUCBT) are feasible options for treating patients with high-risk acute myelogenous leukemia (AML). This study compared outcomes after dUCBT and haplo-HCT using peripheral blood stem cells (PBSCs) in adult patients with AML in complete remission (CR) who underwent transplantation in European Society for Blood and Marrow Transplantation (EBMT)-affiliated centers. In a population of adults with de novo AML in first or second CR, we compared outcomes after dUCBT (n = 165) and after haplo-PTCY PBSC (n = 544) performed between January 2013 and December 2018. Patients receiving in vivo antithymocyte globulin, Campath, or ex vivo T cell depletion were excluded. The median follow-up was 33 months for the haplo-PTCY arm and 52 months for the dUCBT arm. No statistically significant differences were observed between the 2 arms in the rates of grade II-IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 1.31; P = .18), grade III-IV acute GVHD (HR, 1.17; P = .56), chronic GVHD (HR, .86; P = .48), relapse (HR, 1.07; P = .77), nonrelapse mortality (NRM) (HR, .94; P = .77), leukemia-free survival (LFS) (HR, .99; P = .95), or overall survival (OS) (HR, .99; P = .97). Favorable cytogenetic risk was the sole factor predictive of lower relapse incidence (RI). Younger age at transplantation was associated with lower NRM and higher LFS and OS. Both dUCBT and haplo-PTCY with PBSCs can be considered valid approaches for adult AML patients in CR. New strategies should be investigated in both settings to define the most appropriate conditioning regimen and potentially decrease RI and NRM through better immune reconstitution and optimal supportive care.

Leukemia relapse following unmanipulated haploidentical transplantation: a risk factor analysis on behalf of the ALWP of the EBMT.

BACKGROUND: As information on incidence, risk factors, and outcome of acute leukemia (AL) relapse after unmanipulated haploidentical stem cell transplantation (haplo-SCT) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. METHODS: Among 1652 transplants performed for lymphoblastic and myeloid AL between 2007 and 2014, 587 patients (acute lymphoblastic leukemia (ALL) 131, acute myeloid leukemia (AML) 456) with detailed information were analyzed aiming to identify risk factors for post-transplant relapse and for overall survival (OS) after relapse. RESULTS: The cumulative incidence of relapse at 3 years was 44% (35-53%) for ALL and 32% (27-36%) for AML (p = 0.023). In ALL, risk factors for relapse were disease status different from the first complete remission (CR1) at haplo-SCT (CR2 vs CR1: HR 2.85, p = 0.011; advanced vs CR1: HR 14.28, p < 0.0001) and male donor gender (HR 3.64, p = 0.0002), while in AML, risk factors were advanced disease at haplo-SCT (advanced vs CR1: HR 3.95, p < 0.0001) and comorbidities (HCT-CI) ≥ 3 (HR 1.75, p = 0.014). Transplants performed in more recent years were associated with lower relapse incidence (RI) in AML, but not in ALL (HR 0.91, p = 0.042). After relapse, median follow-up was 13 months (mos). OS at 1-year post relapse was 18%. Prognostic factors for superior OS after relapse were remission at time of haplo-SCT (CR vs advanced: HR 0.71, p = 0.028), time from transplant to relapse (≥ 5 mos vs < 5 mos: HR 0.530, p < 0.0001), and bone marrow as a stem cell source (peripheral blood (PB) vs bone marrow (BM): HR 1.473, p = 0.016). CONCLUSIONS: Risk factors for relapse after haploidentical transplantation were disease specific. Longer OS after relapse was achieved in particular by patients both in CR at haplo-SCT and relapsing more than 5 months after transplant (1-year OS 33%).