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

Haploidentical hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy) graft-versus-host-disease (GVHD) prophylaxis yields similar overall survival (OS) as HLA-matched-unrelated donor (MUD) HCT with conventional prophylaxis. Given 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 [hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.10-1.71, p=0.005]; 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<0.001), poor cytogenetics (61% vs 51%, respectively, p=0.44), Philadelphia chromosome-negative (53% vs 48%, respectively, p=0.38), received bone marrow graft (42% vs 16%, respectively, p<0.001) and reduced-intensity conditioning (45% vs 23%, respectively, p<0.001). In multivariate analysis, the older MUD group was associated with a significantly higher risk of chronic GVHD [HR 1.91, 95% CI 1.28-2.85, p=0.002], higher non-relapse mortality (HR 2.75, 95% CI 1.51-4.99, p=0.001), lower relapse (HR 0.50, 95% CI 0.31-0.82, p=0.006) and poorer OS (HR 1.77, 95% CI 1.16-2.71, p=0.008). Despite a higher risk of relapse, younger donor haploidentical HCT with PTCy prophylaxis may be preferred over an older MUD HCT with conventional prophylaxis in patients with ALL due to lower nonrelapse mortality and better OS. Further analysis comparing the effect of donor age in haploidentical-PTCy vs MUD-PTCy is warranted.