Recent advances in hematopoietic cell transplantation for inherited bone marrow failure syndromes

Abstract

Inherited bone marrow failure syndromes (IBMFSs) are a group of rare genetic disorders characterized by bone marrow failure with unique phenotypes and predisposition to cancer. Classical IBMFSs primarily include Fanconi anemia with impaired DNA damage repair, dyskeratosis congenita with telomere maintenance dysfunction, and Diamond-Blackfan anemia with aberrant ribosomal protein biosynthesis. Recently, comprehensive genetic analyses have been implemented for the definitive diagnosis of classic IBMFSs, and advances in molecular genetics have led to the identification of novel disorders such as AMeD and MIRAGE syndromes. Allogeneic hematopoietic cell transplantation (HCT), a promising option to overcome impaired hematopoiesis in patients with IBMFSs, does not correct nonhematological defects and may enhance the risk of secondary malignancies. Disease-specific management is necessary because IBMFSs differ in underlying defects and are associated with varying degrees of risk for clonal evolution and early or late complications after HCT. In addition, long-term follow-up is essential to detect complications related to the IBMFS or HCT. This review provides a summary of current clinical practices along with the latest data on HCT in IBMFSs.

An atypical patient with bone marrow failure syndrome‐2 without microcephaly and learning disability in a Chinese family

“…6 Allogeneic haematopoietic stem cell transplantation (Allo-HSCT) remains the only curative measure for IBMFS but possibly increases the malignant transformation risk. 7 Moreover, somatic abnormalities or other non-hematological alterations already present are irreversible. Here, we reported the first BMFS2 case from a consanguineous Chinese family.…”

Pediatric Bone Marrow Failure: A Broad Landscape in Need of Personalized Management

“…Congenital amegakaryocytic thrombocytopenia (CAMT) is characterized by ineffective megakaryopoiesis and causes severe thrombocytopenia at birth which gradually progresses into pancytopenia during the first years of life [140,141]. In the majority of cases, CAMT is caused by mutations in the MPL gene encoding for the thrombopoietin (THPO) receptor [141].…”

Inherited bone marrow failure syndromes: a review of current practices and potential future research directions

“…For anaemia, corticosteroids are effective in 80% of patients [56–58]. Red blood cell transfusions are used for those resistant to corticosteroids, and iron chelation is often needed to prevent the multiple complications of iron overload [59,60 ▪▪ ]. The only curative therapy is HCT [56,60 ▪▪ ].…”

“…Red blood cell transfusions are used for those resistant to corticosteroids, and iron chelation is often needed to prevent the multiple complications of iron overload [59,60 ▪▪ ]. The only curative therapy is HCT [56,60 ▪▪ ]. Interestingly, some patients with DBA can have spontaneous remission of their red cell aplasia, though the mechanism of this is unknown.…”