Comparison of haploidentical donors for pediatric patients undergoing hematopoietic stem cell transplantation: 10-year outcomes from a single-center experience

Abstract

Abstract Introduction: Donor age is one of the main prognostic factors in haploidentical transplantation, particularly in relation to the incidence and severity of graft-versus-host disease (GVHD).¹ Several studies have indicated that, in pediatric patients, siblings may represent the best donor option due to their younger age and potentially more favorable immunological profile—especially if they are male, HLA-DR and DP matched, and compatible in CMV status and ABO blood group.² Objectives: To compare overall survival and the incidence of acute and chronic GVHD according to donor type—parents or siblings—in a cohort of 85 pediatric patients who underwent haploidentical transplantation at a single center. Materials and Methods: A retrospective study of 85 pediatric patients under 16 years of age who underwent related haploidentical hematopoietic stem cell transplantation with peripheral blood stem cells and post-transplant cyclophosphamide for GVHD prophylaxis, between January 2015 and December 2025 at a single institution. In 70 cases, the donors were one of the parents, while in the remaining 15 cases, the donor was a sibling. The median follow-up for the cohort was 26 months (95% CI: 16–31 months). Results: Clinical characteristics of the 85 patients at the time of hematopoietic stem cell transplantation (HSCT) and their donors are summarized in Table 1. The median time to neutrophil engraftment was 15 days (interquartile range [IQR], 13.5–17.0), and to platelet engraftment was 16 days (IQR, 14.0–20.0) for the entire cohort. The incidence of grade II-IV acute GVHD was significantly higher in transplants with parental donors, with a frequency of 49.5% (95% CI: 35.1–61.8%), compared to 15.2% (95% CI: 0.4–28.5%) in transplants from sibling donors (p = 0.015). Moderate to severe chronic GVHD incidence in parental donor transplants was 24.2% (95% CI: 14–35.8%) at 12 months and 26.5% (95% CI: 15.7–38.6%) at 24 months. In contrast, no cases of moderate or severe chronic GVHD were observed in transplants from sibling donors, a statistically significant difference (p = 0.047). Overall and disease-free survival at 24 months were in the sibling donor group compared to the parental donor group, although it was not statistically significant (68.8% vs. 59.7%, p = 0.454, and 61.8% vs. 55.1%, p = 0.561, respectively). The 24-month cumulative incidence of relapse was higher in the sibling donor group, at 38.2% (95% CI: 12.4–64.2%), compared to 24.9% (95% CI: 14.6–36.6%) in the parental donor group, although this difference did not reach statistical significance (p = 0.222). On the other hand, non-relapse mortality (NRM) at 24 months was significantly higher in transplants with parental donors, with an incidence of 20.0% (95% CI: 11.2–30.6%), versus no cases in the sibling donor group (p = 0.043). Causes of NRM included infection in 8 cases, GVHD in 5 cases, and hemophagocytic lymphohistiocytosis in 1 case. Conclusions: Our findings suggest clinical benefits in using sibling donors over parental donors in both short- and long-term outcomes, particularly regarding the incidence of both acute and chronic GVHD in pediatric patients undergoing haploidentical transplantation.