Haploidentical versus HLA-matched sibling donor HCT with PTCy prophylaxis: HLA factors and donor age considerations

• Haploidentical-HCT, especially with younger donors, may offer comparable outcomes to MSD-PTCy HCT

• In older patients, 'younger' haploidentical B-leader matched donors HCT had superior OS than older MSD

HLA-matched sibling donors (MSDs) are preferred for hematopoietic cell transplantation (HCT). However, the use of alternative donors, especially haploidentical, is increasing, as is our understanding of the impact of HLA factors such as B-leader and DRB1-matching on its outcomes. Yet, data comparing these donor types, particularly considering these HLA factors, is lacking. Herein, we compared haploidentical-HCT (n=1052) to MSD-HCT (n=400), both with posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis. The haploidentical group included older patients (median 49 vs. 46 years) with younger donors (39 vs. 45 years) compared to MSD recipients. Other characteristics were similar. In multivariate analysis, haploidentical group had similar overall survival (OS) [hazard ratio (HR), [95% confidence interval] 0.94, [0.78-1.14], p=.54], non-relapse mortality (HR 0.98 [0.72-1.32], p=.87) and relapse (HR 0.87, [0.70-1.08], p=.20) as the MSD group. Younger donors age was a significant predictor of improved OS. Next, we directly compared the outcomes of 'younger' haploidentical (donor age <35 years, n=347) versus an 'older' MSD (donor age >=50 years, n=143) in 'older' recipients (patient age >=50 years). Patients with 'younger' haploidentical B-leader matched donors had significantly superior OS (HR 0.65, [0.48-0.90], p=.009) compared to 'older' MSD group. Additionally, patients with 'younger' DRB1-mismatched haploidentical donors (HR 0.63 [0.46-0.87], p=.004) had significantly lower risk of relapse than 'older' MSDs. Our study suggests that haploidentical-HCT may offer comparable outcomes to MSD-PTCy HCT. Moreover, among 'older' patients, a 'younger' haploidentical B-leader matched donor might be preferable to an 'older' MSD. These findings need validation in larger datasets.