Allogeneic hematopoietic stem cell transplantation from HLA-matched related and unrelated donors with post-transplant cyclophosphamide in children with inborn errors of immunity

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Introduction. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the mainstay of treatment for the most severe inborn errors of immunity; however, its efficacy is limited by graft-versus-host disease (GVHD). Post-transplant cyclophosphamide (PTCy) is widely used in haploidentical transplantation but its application in HLA-matched pediatric HSCT remains limited. Materials and methods. We conducted a single-center prospective study including 70 patients with inborn errors of immunity who underwent HSCT from HLA-matched related (n = 10) and unrelated donors (n = 60). All the patients received PTCy on days +3 and +4 and ruxolitinib orally from day +5 as GVHD prophylaxis. The median follow-up was 1.7 years. Results. Engraftment was achieved in 69 (98%) patients; the median time to neutrophil and platelet recovery was 24 and 18 days, respectively. Grade II–IV acute GVHD occurred in 37% of the patients and grade III–IV was observed in 24%. Notably, there were no cases of grade III–IV acute GVHD among the patients transplanted from an HLA matched related donor. Chronic GVHD developed in 11.5% of the patients. The cumulative incidence of cytomegalovirus, adenovirus, and Epstein–Barr virus reactivation was 21%, 7.1%, and 29%, respectively. Post-transplant lymphoproliferative disorder developed in 7.1% of the patients; the use of rituximab in the conditioning regimen was associated with a lower incidence of Epstein-Barr virus reactivation (p 0.001). Overall survival was 89% and event-free survival was 85%. Transplant-associated toxicity was generally moderate and mainly represented by mucositis. Conclusion. Here we demonstrated our own experience with HSCT and PTCy in children with inborn errors of immunity. Especially notable were good engraftment rates combined with the low toxicity profile of HSCT and the low probability of GVHD following HSCT from an HLA-matched related donor. Unfortunately, the patients transplanted from an unrelated donor had a high risk of developing severe GVHD which, although comparable to the results reported by several other research groups, did not meet current safety requirements for the procedure. This may serve as an argument in favor of further refinement of the method or modification of approaches to GVHD prevention.

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