Haploidentical Bone Marrow Transplantation for Wiskott-Aldrich Syndrome

Introduction: Wiskott-Aldrich syndrome (WAS) is an X-linked disorder caused by mutations in the WAS gene, which encodes the WAS protein involved in actin polymerization. WAS is a rare syndrome affecting approximately 1 in 100,000 live births. Hematopoietic stem cell transplantation is the mainly curative option for WAS. In this study, the outcome of Haplo-BMT in four patients with WAS was investigated.

Methods: Four patients with WAS, who were confirmed with frameshift mutation in the WAS gene, were treated with haploidentical bone marrow transplant (haplo BMT) in second hospital of Dalian Medical University (China) from May 2018 to July 2024. The follow-up period was up to July 31, 2024. Flu/Bu/Cy/ATG was used as conditioning regimen, containing fludarabine (Flu, 30 mg/m²) once a day for 4 consecutive days, Busulfan (Bu, 0.8 mg/kg) four times a day for 4 days, cyclophosphamide (Cy, 30 mg/kg) once a day for 2 days, and rabbit ATG (SangStat, France) of 2.5 mg/kg once a day for 4 days. G-CSF-primed HSCTs plus marrow grafts were infused into recipients. Father served as blood stem cell donor.

Results: Four patients with were retrospectively collected, who had median age of 1.8 (range, 0.4-14) years. They received a median mononuclear cell number of 18.7 (range, 14.2-24.0) × 10⁸/kg of body weight, or median CD34⁺ cell number of 12.9 (range, 10.3-14.9) × 10⁶/kg of body weight. They were all successfully engrafted with a median time for neutrophil or platelets of 12 (range, 11-16) days and 12 (range, 11-14) days, respectively. One developed limited chronic graft versus host disease, and he well recovered by treating with methylprednisolone (1 mg/kg/day) and tacrolimus. One patient died of transplantation associated thrombotic microangiopathy at 8 months post-transplantation. Four patients with overall survival is 75%, with a median follow-up time of 26 (range, 2.5-48) months.

Conclusion: This retrospective investigation indicated haplo-BMT is feasible for a long-term overall survival in pediatric patients with WAS.

No relevant conflicts of interest to declare.