Pediatric myelodysplastic syndromes

Abstract

Pediatric myelodysplastic syndromes (MDS) are a group of rare clonal hematopoietic stem cell disorders characterized by varying degree of cytopenias, ineffective and dysplastic hematopoiesis, and the risk of leukemic transformation. The clinical, laboratory, and histologic presentation of pediatric MDS shares significant overlap with other inherited and acquired bone marrow failure (BMF) disorders. Given that the majority of pediatric patients with MDS present with a hypocellular bone marrow, the histopathologic diagnosis is challenging and usually requires ancillary molecular studies. 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 pediatric and young adult patients with MDS have an underlying genetic predisposition. Nevertheless, the molecular underpinnings remain poorly understood in most cases. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment option. 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 of pediatric MDS and address clinical, laboratory, and pathologic features, as well as diagnostic criteria, genomic advances, and therapeutic options and prognosis.