Haploidentical Hematopoietic Cell Transplantation with Posttransplant Cyclophosphamide for Children with Non-Malignant Disease

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Background Haploidentical hematopoietic cell transplantation (haplo-HCT) with posttransplant cyclophosphamide (PTCy) is widely used as an alternative donor transplant , but the evidence in pediatric patients is insufficient, especially for non-malignant disease (NMD). The aim of this study is to verify the safety and efficacy of haplo-HCT with PTCy for children with NMD by performing a single center retrospective analysis. Patients and Methods With the ethics committee approval, we reviewed medical records and performed a retrospective analysis of the transplant outcomes of NMD patients who underwent haplo-HCT with PTCy from March 2017 to March 2024 at our center. A total of 21 pediatric patients (female 5, male 16) were eligible, with a median age at HCT of 6 years old (range, 0-16). The underlying disease consisted of inborn errors of immunity (n = 9), bone marrow failure (n = 6), Epstein-Barr (EB) virus associated disease 5, and inborn errors of metabolism (n = 1). Sixteen patients were treated with the busulfan-based regimen consisting of targeted busulfan , fludarabine , anti-thymocyte globulin, and low-dose total body irradiation . All patients received PTCy (40-50 mg/kg/day on day 3 and 4) with tacrolimus (from day 5) and mycophenolate mofetil (from day 5 to 35). The median observation period of survivors was 52 months, ranged with 7-89 months. Results Eighteen patients achieved engraftment (neutrophil > 0.5 × 10 9 /L) with median day 15 [range, 11-26]. The cumulative incidence (CI) of engraftment at day 35 was 86 %, and the CIs of reticulocyte > 1% and platelet > 20 × 10 9 /L at day 50 were 76% and 57%, respectively (Fig. A). No patient experienced acute heart failure associated with PTCy. The CIs of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD) at day 100 and chronic GVHD at 4 years were 29 %, 10 %, and 10 %, respectively (Fig. B). The CIs of cytomegalovirus antigenemia, EB viremia , hemorrhagic cystitis , and sinusoidal obstructive syndrome at day 100 were 14 %, 5 %, 14 %, and 10 %, respectively. The chronic GVHD-free/failure-free survival rate and the overall survival rate at 4 years were 75% and 85%, respectively (Fig. C). Three patients died during the observation period, two due to progression of the underlying disease (EB virus-associated hemophagocytic lymphohistiocytosis) before engraftment and one due to pulmonary chronic GVHD oon day 759. Conclusion Our analysis suggests that haplo-HCT with PTCy for pediatric patients with NMD may have comparable outcomes to other alternative donor HCT in children. Additionally, it may be necessary to consider SOS, hemorrhagic cystitis , and viral infection in PTCy-haplo HCT. The long-term feasibility of PTCy in pediatric patients is a future issue because of concerns about the increased risk of late-onset complications such as gonadal dysfunction and secondary cancers .

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.