Advanced MDS in Children

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic disorders characterized by cytopenia and dysplasia. Of those, peripheral blood blasts with 2–19% or bone marrow blasts with 5–19% are classified as advanced MDS. Aging-related somatic variants acquired in the hematopoietic cells are associated with the pathogenesis of adult MDS, whereas pediatric MDS often occurs in the context of germline predispositions. Besides well-known inherited bone marrow failure syndromes, germline mutations in SAMD9/SAMD9L and GATA2 are commonly found in children and adolescents with primary MDS, and the frequency was 8% and 7%, respectively. Half of patients with pediatric MDS harboring monosomy 7 have these mutations. The differential diagnosis from de novo AML with low blast count is sometimes challenging. Clinical features, disease course, cytogenetic findings, and histopathologic findings should be carefully evaluated to differentiate those features suggestive of germline predisposition and poor prognostic features. Myeloablative allogeneic hematopoietic cell transplantation is generally considered as the only curative option; however, both relapse and transplantation-related mortality are still the major cause of treatment failure. Pre-transplant intensive chemotherapy should be considered for cases that progress to bone marrow blast count exceeding 20–30%. Azacitidine may be an effective option as a bridge to transplantation.