Adult-onset hereditary myeloid malignancy and allogeneic stem cell transplantation

Hereditary myeloid malignancies, especially in adults or elderly persons, had been considered quite rare before the next-generation sequencing era; however, increased usage of clinical sequencing has revealed much higher prevalence of inherited myeloid malignancies. DDX41 and various pathogenic germline mutations have newly been recognized as the cause of adult-onset familial leukemia and myeloid malignancies. Although germline predisposition to myeloid neoplasms had been categorized as a provisional entity in the World Health Organization classification of hematopoietic neoplasms in 2016, methodology for the identification of hereditary myeloid malignancies has not been fully established yet. In addition, many unresolved problems, such as epidemiology, the exact pathogenic mechanisms, and ideal treatment strategy, including indications of allogeneic hematopoietic stem cell transplantation, still remain. Related donor selection for stem cell transplant is a particularly sensitive issue due to the possibility of germline mutation of the candidate relatives and the risk of donor cell leukemia after transplantation. Here, we reviewed the current evidence regarding epidemiology, diagnosis, mechanisms of progression, and transplantation strategy for hereditary myeloid malignancies.