Size does not always matter: limited impact of donor-recipient weight difference on outcomes of adult allogeneic peripheral blood stem cell hematopoietic cell transplantation.

Background: Allogeneic hematopoietic cell transplantation (HCT) relies on careful donor selection to optimize outcomes and minimize complications such as graft-versus-host disease (GVHD). While human leukocyte antigen (HLA) matching remains central to donor selection, secondary characteristics such as age, sex, cytomegalovirus serostatus, and donor-recipient weight difference have become increasingly relevant. Previous studies have demonstrated a relationship between donor-recipient weight ratio and stem cell dose, which may, in turn, influence outcomes including engraftment, survival, relapse, and GVHD. Despite evidence suggesting that donor weight affects CD34+ cell dose per unit of recipient weight, the specific impact of donor-recipient weight difference on transplant outcomes remains unclear.

Objective: This study aims to evaluate the effect of donor-recipient weight disparity on post-transplant outcomes in adult allogeneic HCT, thereby informing donor selection when multiple suitable donors are available.

Study design: This retrospective cohort study included 841 consenting patients 18 years of age or older who underwent allogeneic HCT using peripheral blood stem cells (PBSC) as the source of graft at the Princess Margaret Hospital Cancer Centre between January 1, 2018, and April 30, 2023. Collected variables included patient and donor weight, clinical and demographic characteristics, transplant regimen details, engraftment time, stem cell dose, survival outcomes, incidence of GVHD, and secondary complications. Conditioning regimens and GVHD prophylaxis varied by donor type, with protocol changes implemented during the study period. Primary outcomes included overall survival (OS), relapse-free survival (RFS), non-relapse mortality (NRM), cumulative incidence of relapse, and incidence of GVHD, CMV and EBV reactivation, and bloodstream infections. Statistical analyses included Mann-Whitney U test, chi-squared test, Kaplan-Meier survival estimates with log-rank testing, and Cox proportional hazards modeling for univariate and multivariate analysis. All analyses were conducted using TIBCO Statistica® 13.5.

Results: Among 841 patients, the median donor-recipient weight difference was 1.3 kg (range: -82 kg to +128 kg). When donor-recipient weight difference was analyzed as a continuous variable, the use of heavier donors was associated with higher CD34+ dose (r=0.2956, P<0.001) and increased risk of chronic GVHD (HR 1.07, P=0.036). Weight difference was not significantly associated with OS, RFS, relapse, or risk of acute GVHD. The use of heavier donors was associated with decreased risk of NRM in univariate (HR 0.93, P=0.05) and multivariate (HR 0.93, P<0.05) analyses.

Conclusion: The use of heavier donors in PBSC allogeneic HCT is associated with higher CD34+ cell dose, but its impact on transplant outcomes is limited, being associated only with a small decrease in the incidence of NRM and increase in the incidence of chronic GVHD. The findings are likely confounded by CD34+ cell dose, which itself is associated with rates of chronic GVHD and CMV reactivation. Overall, donor-recipient weight disparity has minor impact on PBSC HCT outcomes in adults and should therefore be given limited consideration during donor selection.