Pediatric myelodysplastic syndromes

Abstract

Pediatric myelodysplastic syndromes (MDS) are a group of rare clonal hematopoietic stem cell disorders characterized by dysplasia and ineffective hematopoiesis with high risk for leukemic transformation to acute myeloid leukemia. The clinical, laboratory, and histologic presentation of pediatric MDS shares significant overlap with inherited and acquired bone marrow failure disorders, which makes the diagnosis challenging. Definitive diagnosis of pediatric MDS usually requires a comprehensive diagnostic approach including clinical and molecular genetic assessment by an experienced pediatric hematologist in conjunction with careful evaluation of the bone marrow by a specialized hematopathologist. While rapid advancements have been made in the field of adult MDS, the underlying genetics and pathophysiology of pediatric MDS are still poorly understood. The recent discovery of germline mutations in GATA2 leading to MDS suggests that some children and young adults with MDS have an underlying genetic predisposition. Hematopoietic stem cell transplantation (HSCT) remains the only curative therapy for MDS but carries significant risk for relapse, transplant-related toxicities, and mortality. Optimal timing of HSCT is not often straightforward, as some pediatric patients with low-grade MDS have an indolent disease course, while others show rapid progression to advanced MDS and leukemia. Lastly, the classification of pediatric MDS has evolved over the years and is different from the terminology currently used in adult MDS. This review will focus on the current classification schemes and diagnostic criteria of pediatric MDS. It will address clinical, laboratory, and pathologic features of MDS, genetic and genomic advances, and therapeutic options and prognosis.