Haploidentical Versus Matched Sibling Donor HCT in Racially Diverse Pediatric and AYA Patients with Hematologic...

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for pediatric patients with hematologic malignancies. Human leukocyte antigen (HLA)-matched sibling donors (MSDs) are considered the optimal source for stem cell transplantation; however, up to 70% of patients lack an MSD. This disparity is particularly pronounced among racial and ethnic minorities, who face challenges in identifying matched unrelated donors (MUDs). Haploidentical (haplo) donors are nearly universally available and have become viable alternatives with post-transplant cyclophosphamide (PT-CY) improving immune reconstitution and reducing graft-versus-host disease (GvHD). While adult studies have demonstrated comparable outcomes between haplo-HCT and MSD-HCT, pediatric data remain limited, especially in racial and ethnic minority populations.

This study aimed to compare the clinical outcomes of myeloablative conditioning (MAC) haplo-HCT versus MSD-HCT in pediatric and adolescent/young adult (AYA) patients with hematologic malignancies, predominantly from Hispanic and other minority backgrounds.

A retrospective single-center analysis was conducted on 72 pediatric and AYA patients (0-28 years) with hematologic malignancies who underwent MAC followed by either T-cell-replete haplo-HCT (n=43) or MSD-HCT (n = 29) between October 2013 and March 2025. Conditioning regimens included total body irradiation (TBI)- or busulfan-based protocols. GvHD prophylaxis consisted of PT-CY ± bendamustine (PT-BEN) with tacrolimus-mycophenolate mofetil (haplo-HCT) or methotrexate-cyclosporine (MSD-HCT).

At a median follow-up of 39.4 months (MSD-HCT) and 48.7 months (haplo-HCT), OS was 74.5% for MSD-HCT and 70.1% for haplo-HCT (P = .89), while LFS was 70.6% and 67.8%, respectively (P = .87). Relapse rates (26.8% vs. 23.0%; P = .49) and NRM (13.1% vs. 9.8%; P = .95) were comparable between groups. The cumulative incidence of grade III-IV acute GvHD was higher, though not statistically significant, in haplo-HCT (19.4% vs. 7.3%; P = .17), whereas chronic GvHD rates were 35.9% (MSD) vs. 23.9% (haplo) (P = .25). GvHD-free, relapse-free survival (GRFS) was 60.1% for MSD-HCT versus 54.1% for haplo-HCT (P = .83). Haplo-HCT recipients had higher rates of cytomegalovirus (CMV) reactivation requiring therapy (40% vs. 7%; P = .002). Donor age was independently associated with increased chronic GvHD risk in multivariable analyses.

In this predominantly Hispanic pediatric and AYA cohort, haplo-HCT with PT-CY achieved survival, relapse, and NRM outcomes comparable to MSD-HCT, supporting its role as a practical alternative when MSDs are unavailable. Although haplo-HCT was associated with a higher risk of CMV reactivation and a non-significant trend toward increased severe acute GvHD, overall GvHD rates were manageable. Donor age emerged as a key predictor of chronic GvHD, underscoring its importance in haploidentical donor selection. These findings highlight haplo-HCT as an effective and accessible transplant option for minority populations with limited donor availability.