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.
Aljawai et al. (Sun,) studied this question.