Hematopoietic cell transplantation in inherited bone marrow failure syndromes

Inherited bone marrow failure syndromes (IBMFS) comprise a heterogeneous group of rare genetic disorders characterized by defective hematopoiesis, congenital anomalies, and a predisposition to clonal evolution and malignancies. Hematopoietic cell transplantation remains the only curative option for the hematologic manifestations of these disorders, although it does not correct congenital malformations or eliminate the long-term risk of non-hematopoietic cancers. This review summarized current evidence and transplantation strategies for major IBMFS, including Fanconi anemia, dyskeratosis congenita/telomere biology disorders, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, congenital neutropenia, congenital amegakaryocytic thrombocytopenia, and other inherited thrombocytopenias. We discussed disease-specific transplant indications, donor selection, conditioning regimens, graft source preferences, and outcomes across different patient populations. Advances in reduced-intensity conditioning and post-transplant cyclophosphamide have expanded donor availability, improving survival even with alternative donors. Nevertheless, long-term challenges persist, such as increased risks of solid tumors, endocrine dysfunction, and organ toxicity, emphasizing the need for multidisciplinary care and lifelong surveillance. Optimal outcomes depend on timely referral to specialized centers, meticulous donor screening, and individualized transplant strategies tailored to the unique biology of each disorder.