Expanding access in pediatrics: Outcomes of haploidentical transplantation with reduced intensity and peripheral blood stem cells

Abstract Introduction: The growing complexity of health systems limits equitable access to hematopoietic stem cell transplantation (HSCT). The availability of haploidentical donors in over 95% of cases and the use of reduced-intensity conditioning (RIC), which in adults has yielded results comparable to myeloablative conditioning, provides an alternative to expand access and improve outcomes in the region. Objective: To describe the outcomes in pediatric patients undergoing haploidentical HSCT (Haplo-HSCT) with graft-versus-host disease (GVHD) prophylaxis using post-transplant cyclophosphamide (PTCy) and a RIC regimen. Methods: A retrospective study was conducted at a single center, including pediatric patients under 14 years old with hematological malignancies, enrolled in a prospective registry between January 2015 and April 2024. All patients received related Haplo-HSCT with peripheral blood stem cells. A RIC with Flu/Cy/Bu8 or Flu/Cy/Mel140 + 2 Gy total body irradiation (TBI) was used. GVHD prophylaxis was PTCy based. Results: Forty-seven patients were included, with a median age of 8 years (1–14), of whom 92% had acute leukemia. Sixty percent were in second remission, and 40% had received three or more prior treatment lines. In 60% of cases, the donor was the father, with a median age of 31 years. Two patients (4%) experienced primary graft failure, both with the Flu/Cy/Bu8 regimen. Eighty-five percent received conditioning with Flu/Cy/Mel140 and 2 Gy radiotherapy. The median time to neutrophil engraftment was 14 days, and 15 days for platelets. The cumulative incidence of acute graft-versus-host disease (aGVHD) grades II-IV at day 100 was 36%, and grades III-IV was 12.7%. The cumulative incidence of moderate to severe chronic GVHD at 12 months was 21%. Non-relapse mortality (NRM) at one year was 14.8%, and the cumulative incidence of relapse at two years was 21.9%. Overall survival (OS) was 79% at one year and 68% at two years, while event-free survival (EFS) at two years was 63%. Conclusion: The outcomes of this pediatric cohort undergoing haploidentical HSCT with PTCy, using a reduced-intensity conditioning regimen and peripheral blood hematopoietic stem cells, demonstrated acceptable toxicity, overall survival, and event-free survival. Sharing this experience contributes to collective knowledge, highlights the challenges faced, and may motivate other teams in similar settings to implement this therapeutic strategy.