Haploidentical vs matched unrelated donors for patients with ALL: donor age matters more than donor type

Haploidentical hematopoietic cell transplantation (HCT) with posttransplant cyclophosphamide (PTCy) graft-versus-host-disease (GVHD) prophylaxis yields a similar overall survival (OS) to HLA-matched unrelated donor (MUD) HCT with conventional prophylaxis. Given the prognostic implications of donor age, we investigated the impact of donor age (younger [<35 years, n = 868] vs older [≥35 years, n = 418]) and donor type (haploidentical [n = 373] vs MUD [n = 913]) on OS in adult patients with acute lymphoblastic leukemia (ALL). Older donor age was independently associated with significantly poor OS, whereas donor type was not. Next, we directly compared the outcomes of a younger haploidentical donor (n = 187) vs an older MUD (n = 232). In this cohort, more patients in the haploidentical group had B-cell immunophenotype (89% vs 77%, respectively, P < .001), poor cytogenetics (61% vs 51%, respectively, P = .44), Philadelphia chromosome-negative (53% vs 48%, respectively, P = .38), received bone marrow graft (42% vs 16%, respectively, P < .001), and reduced-intensity conditioning (45% vs 23%, respectively, P < .001). In the multivariate analysis, the older MUD group was associated with a significantly higher risk of chronic GVHD, higher nonrelapse mortality (NRM), lower relapse, and poorer OS. Despite a higher risk of relapse, younger donor haploidentical HCT with PTCy prophylaxis may be preferred over older MUD HCT with conventional prophylaxis in patients with ALL due to lower NRM and better OS. Further analysis comparing the effect of donor age in haploidentical PTCy vs MUD PTCy is warranted.