2024 Volume 61 Issue 5 Pages 313-317
Inherited bone marrow failure syndromes (IBMFSs) are a heterogeneous group of hematological disorders characterized by impaired hematopoietic cell proliferation, differentiation, and various external malformations. IBMFSs also serve as cancer and leukemia predisposition syndromes, with a high risk of developing myelodysplastic syndrome or acute myeloid leukemia and, in some cases, solid tumors. IBMFSs account for 10–20% of childhood bone marrow failures, with Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome being the most common diseases. Differentiating IBMFSs from acquired bone marrow failures such as aplastic anemia is crucial for determining the appropriate treatment, including hematopoietic cell transplantation (HCT). IBMFS diagnosis relies on hematological examination, family history assessment, identification of specific external surface malformations, and disease-specific screening. With advancements in genetic analysis, many causative genes have been identified, facilitating the comprehensive genetic analysis and differential diagnosis of IBMFS. Allogeneic hematopoietic stem cell transplantation is a promising treatment option for addressing bone marrow disorders in patients with IBMFS. However, it is essential to note that HCT does not improve non-hematologic pathologies and may increase the risk of secondary malignancies due to inherited cancer predisposition. Therefore, careful consideration of the graft donor selection and determination of the conditioning regimen are necessary. Additionally, monitoring the late effects of HCT and age-related complications in patients with IBMFS is important to provide appropriate counseling, surveillance, and treatment.
