Allogeneic Hematopoietic Stem Cell Transplantation in Children with Mendelian Susceptibility to Mycobacterial Diseases Caused by Interferon Gamma Receptor 1 Deficiency and Literature Review

Abstract Purpose IFNGR1 deficiency is a rare primary immunodeficiency causing severe disseminated mycobacterial infections. HSCT is the only curative option, but reports of success are limited and optimal graft/TCD strategies remain unclear. We aimed to evaluate the safety and efficacy of peripheral blood stem cell transplantation with in vivo TCD for IFNGR1 deficiency using alternative donors. Methods We retrospectively analyzed three pediatric patients with complete IFNGR1 deficiency who received HSCT at our center and performed a systematic literature review. Results All three patients lacked HLA-matched sibling donors and received PBSC grafts with in vivo TCD (ATG and/or post-transplant cyclophosphamide) from alternative donors (10/10 unrelated, 5/10 haploidentical sibling, 8/10 mismatched unrelated). All achieved durable full donor chimerism (>99%) with no grade III-IV acute or extensive chronic GVHD. Manageable complications (PTLD, limited skin/joint/eye GVHD, pulmonary fungal infection) occurred without graft failure or transplant-related mortality. One patient who failed initial transplantation during active infection and elevated IFN‑γ succeeded after infection control, underscoring the critical role of pre-transplant infection management. Conclusion PBSC transplantation with in vivo TCD is safe and effective for complete IFNGR1 deficiency using alternative donors, expanding donor options and avoiding aggressive ex vivo TCD in this vulnerable population.