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Hofmann I.,Dana Farber Boston Childrens Cancer And Blood Disorders Center Boston | Hofmann I.,Harvard University
Journal of Hematopathology | Year: 2015

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. © 2015, Springer-Verlag Berlin Heidelberg.


Hofmann I.,Dana Farber Boston Childrens Cancer And Blood Disorders Center Boston | Hofmann I.,Harvard University
Journal of Hematopathology | Year: 2015

Myeloproliferative neoplasms (MPNs) are a group of clonal hematopoietic stem cell disorders characterized by aberrant proliferation of one or more myeloid lineages often with increased immature cells in the peripheral blood. The three classical BCR-ABL-negative MPNs are (1) polycythemia vera (PV), (2) essential thrombocythemia (ET), and (3) primary myelofibrosis (PMF), which are typically disorders of older adults and are exceedingly rare in children. The diagnostic criteria for MPNs remain largely defined by clinical, laboratory, and histopathology assessments in adults, but they have been applied to the pediatric population. The discovery of the JAK2 V617F mutation and, more recently, MPL and calreticulin (CALR) mutations are major landmarks in the understanding of MPNs. Nevertheless, they rarely occur in children, posing a significant diagnostic challenge given the lack of an objective clonal marker. Therefore, in pediatric patients, the diagnosis must rely heavily on clinical and laboratory factors and exclusion of secondary disorders to make an accurate diagnosis of MPN. This review focuses on the clinical presentation, diagnostic work up, differential diagnosis, treatment, and prognosis of the classical BCR-ABL-negative MPNs (PV, ET, and PMF) in children and highlights the key differences to the adult diseases. Particular attention will be given to pediatric PMF, as it is the only disorder of this group that is observed in infants and young children, and in many ways appears to be a unique entity compared to adult PMF. © 2015, Springer-Verlag Berlin Heidelberg.

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