Impact of Donor Age and Gender on Allogeneic Hematopoietic Stem Cell Transplantation
Authors: McGuirk Matthew , Shahzad Moazzam , Irfan Sohaib , Amin Muhammad Kashif , Chaudhary Sibgha Gull , Anwar Iqra , DeJarnette Shaun , Shune Leyla O. , Abdallah Al-Ola , Singh Anurag K. , McGuirk Joseph P. , Mushtaq Muhammad Umair 
Published: December 2024

Background:

Allogeneic hematopoietic stem cell transplant (allo-SCT) is critical in managing hematologic disorders. Donor age and gender are essential factors for post-transplant outcomes, and younger male donors have been associated with improved outcomes. We aimed to investigate the impact of donor age and gender on outcomes in patients undergoing matched unrelated donor (MUD) and haploidentical (haplo) allo-SCT.

Methods:

For this retrospective single-center study, we included allo-SCT recipients who received a MUD (n=276) or haplo (n=176) SCT at the University of Kanas Medical Center from August 2016 to July 2021. Cox regression analysis compared overall survival (OS) and disease-free survival (DFS). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Logistic regression was performed to compare relapse, non-relapse mortality (NRM), acute and chronic graft versus host disease (GVHD), and GVHD-free Relapse-free survival (GRFS). Odds ratios (0R) with 95% CI were calculated. Linear regression was performed to compare platelet and neutrophil engraftment, and the correlation coefficient (R) was calculated. Multivariate analyses were performed for donor age as a continuous and categorical variable (&lt;30 years vs 30 years and above). SPSS version 28 and R version 4.16 were used for data analysis. Statistical significance was considered at p&lt;0.05.

Results:

We included 452 Allo-SCT recipients who received a MUD (n=276) or Haplo (n=176) SCT. The median recipient age was 57 (18-77) years and 277 (61%) were male. The median age of the donor was 28 (10-65) years, with 57% of donors being younger than 30 years. Seventy-one percent (n=331) of donors were male. Myeloablative and reduced-intensity conditioning were performed in 169 (37%) and 283 (63%) recipients. The graft source was bone marrow in 224 (49.6%), and 228 (50.4%) had peripheral blood stem cell grafts. The median graft cell dose was 4 million CD34 cells/kg. GVHD prophylaxis included tacrolimus/methotrexate (n=241, 53%) and post-transplant cyclophosphamide-based (n=211, 47%). Hematologic diagnoses included myeloid (n=322, 71%), lymphoid (n=101, 22%), and others (n=29, 7%). After adjusting for significant variables in the multivariate regression models, OS was not affected by the donor age (HR 1.005, 95% CI 0.991-1.021, p=0.476) and donor age &lt;30 years (HR 0.923, 95% CI 0.681-1.252, p=0.608). Donor age had a marginal association with relapse (donor age: OR 0.974, 95% CI 0.950-0.997, p=0.032; donor age &lt;30 years: OR 1.760, 95% CI 1.131-2.775, p=0.013) and NRM (donor age: OR 1.025, 95% CI 1.001-1.048, p=0.034; donor age &lt;30 years: OR 0.656, 95% CI 0.417-1.031, p=0.067). The donor's age did not affect GRFS, DFS, acute and chronic GVHD, and engraftment. Allo-SCT with male donors had superior OS (HR 0.626, 95% CI 0.452-0.868, p=0.0049) compared to female donors. Faster platelet engraftment was observed using male donors (R -4.212, -7.90 to -0.517, p=0.0250). GRFS, Relapse, DFS, NRM, acute and chronic GVHD, and neutrophil engraftment were not affected by donor gender.

Conclusion:

The use of male donors was associated with superior overall survival and faster platelet engraftment, while donor age did not significantly impact post-transplant outcomes. Our findings suggest improved survival with the use of male donors regardless of donor age, and these findings should be validated in a larger contemporary cohort.