Older Donor Age Is Not Associated with Inferior Survival in Contemporary Haploidentical Transplantation

Data regarding the association of donor age with haploidentical (haplo) hematopoietic stem cell transplant (HCT) outcomes has been inconsistent, particularly concerning a specific age cutoff. Most published studies predated the advancement in cytomegalovirus prophylaxis, improved graft-versus-host disease (GVHD) treatments, maintenance therapy post-HCT. Examine the role of donor age in a recent cohort of patients, from 2018-2024. We included consecutive adult patients with hematologic malignancies who underwent haplo HCT (n=364) at MD Anderson Cancer Center. All patients received post-transplant cyclophosphamide GVHD prophylaxis. To determine the optimal donor age cutoff associated with overall survival (OS) and progression-free survival (PFS), we explored a series of donor age dichotomizations as well as categorization by 5-year intervals. Our analysis, using dichotomization of donor age, did not reveal a clear donor age cut-off to be associated with either OS or PFS. In the absence of a statistically significant age cutoff for OS or PFS, we categorized donor age into three groups (≤30 [n=155], 31-44 [n=139], and ≥45 [n=70] years) for all subsequent analyses based on cohort distribution and clinical relevance. Compared to donor age ≤30 years, the hazards of OS: (31-44: HR 0.92, P =.69) for donor age 31-44 and (≥45: HR 1.19, P =.43) in multivariable analysis (MVA). PFS mirrored OS. Similar patterns emerged for PFS. Older donor age was associated with increased hazards of non-relapse mortality in MVA: (31-44: HR 1.44,], P =.18) and (≥45: 1.52, P =.14). Consequently, relapse rates were lower in these groups (31-44: 0.55, P =.025) and (≥45: 0.70, P =.29) compared to donors ≤30 years. Older donors were associated with a significantly increased risk of grade III-IV acute GVHD (31-44: 3.77, P =.001; ≥45: 3.83, P =.002) compared to donors ≤30 years. The risk of chronic GVHD was also higher with older donors (31-44: 1.44, P =0.18; ≥45: 1.52, P =.14) compared to younger donors. We noted patient and disease-related factors significantly associated with OS in MVA; older patient age (≥ 65: 1.90 [1.22-2.98], P =.005) and a high/very high disease risk index (DRI) (1.89 [1.38-2.60], P <.001). High/very high DRI associated with a 2.5-fold increased risk of relapse(95% CI 1.63-3.90, P <.001). Our study suggested that dichotomization of donor age did not reveal it to be a major selection factor. However, it remains to be assessed whether HLA factors play a more dominant role, if improved post-HCT strategies have altered the adverse effect of donor age in this population, or if dichotomization may present a limited methodology of modeling donor age and novel approaches need to be adopted in this contemporary era. Despite the lack of survival differences, older donor age remains a significant predictor of severe acute GVHD risk.