Impact of Donor Age on Transplant Outcomes in Matched Unrelated Donor Transplantation for Myelofibrosis.

Abstract

Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF), and donor selection remains one of the few modifiable determinants of outcome. As the unrelated donor pool ages, the impact of donor age in matched unrelated donor (MUD) HCT for MF has become increasingly relevant but remains undefined. To evaluate the impact of donor age on engraftment, graft-versus-host disease (GVHD), and survival after MUD HCT for primary MF, and to examine whether any association could be attributed to an identifiable mechanism. We retrospectively analyzed 132 adults who underwent their first MUD HCT for primary MF between 2000 and 2021 using the Japanese nationwide transplant registry, dichotomized at the median donor age of 41 years (younger, n = 65; older, n = 67). Engraftment, GVHD, non-relapse mortality (NRM) and relapse were analyzed by the Fine-Gray method, and overall survival (OS), disease-free survival (DFS) and GVHD-free, relapse-free survival (GRFS) by the Kaplan-Meier method. Multivariable models were adjusted for prespecified covariates and baseline imbalances. Missing data were handled by multiple imputation. Donor age increased over the study period (r = 0.332, P < .001). Day-50 neutrophil engraftment was similar (89.2% versus 89.6%, P = .868), but after adjustment older donor age predicted slower neutrophil (hazard ratio [HR] 0.65, 95% CI: 0.45 to 0.95, P = .027) and platelet (HR, 0.41, 95% CI: 0.23 to 0.72, P = .002) recovery; the nucleated cell dose of marrow declined with donor age and accounted for this association. Grade III-IV acute GVHD at d 100 was higher with older donors (15.1% versus 1.6%, P < .001; adjusted HR, 13.73, 95% CI: 1.87 to 100.76, P = .010), although events were few. Three-year NRM was 34.4% versus 21.4% (adjusted HR 1.76, 95% CI: 0.91 to 3.40, P = .093) and 3-year relapse was 35.4% versus 26.3% (adjusted HR, 1.36, 95% CI: 0.73 to 2.54, P = .329). Older donor age was associated with inferior 3-year OS (35.1% versus 62.4%; adjusted HR, 2.07, 95% CI: 1.19 to 3.62, P = .010), DFS (HR, 1.73, 95% CI: 1.04 to 2.90, P = .036) and GRFS (HR, 1.86, 95% CI: 1.17 to 2.96, P = .009). In MUD HCT for MF, older donor age was associated with slower engraftment, more severe acute GVHD and inferior survival. The engraftment findings were explained by the lower nucleated cell dose of marrow from older donors, but no mechanism could be identified for the survival difference, and residual confounding cannot be excluded. Donor age should therefore be regarded as an independent prognostic marker available at donor selection rather than a demonstrated causal determinant. In a steadily ageing donor registry, the magnitude of this association supports giving donor age explicit weight when equivalent HLA matches are available.