Pediatric Myeloproliferative Neoplasms

Key points

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by hyperproliferation of the myeloid lineages. The annual incidence in adults is low, with approximately 6 per 100,000 individuals. Typically, the onset of MPN is in the fifth to seventh decade of life, but, rarely, these diseases can occur in the pediatric setting. Because of the rarity of pediatric MPNs, little is known about the natural history, pathology, and molecular features of these cases. Depending on the practice setting, pediatric hematologists may not be familiar with the diagnosis of pediatric MPNs according to current World Health Organization (WHO) criteria; in these situations, hematopathologists can be a useful resource for their clinical colleagues.

In the 1950s, William Dameshek ¹ described 4 myeloproliferative disorders based primarily on their clinical presentation and bone marrow morphology: chronic myeloid leukemia, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). ^1 , 2 Over the ensuing decades, a proliferation of molecular data showed the clonal nature of these MPNs and transformed classification of these neoplasms into an integrated process incorporating clinical, laboratory, morphologic, and molecular findings. In the 1960s and 1970s, the Philadelphia (Ph) chromosome with fusion of BCR and ABL1 was identified as the driver of chronic myeloid leukemia (CML). ^3 , 4 At the turn of the twenty-first century, imatinib was developed as a targeted therapeutic for patients with CML. The JAK2 V617F mutation was identified as a driver mutation in MPN in 2005, followed subsequently by the discovery of MPL and CALR mutations. 567 These driver mutations now play a critical role in the diagnosis and classification of MPN; in patients with CML, BCR-ABL1 transcripts are used as a marker of disease burden.

This article reviews the 4 major myeloproliferative neoplasms using the diagnostic criteria published in the 2016 WHO update, with attention to unique considerations for pediatric patients. Pediatricians are fond of saying that children are not just tiny adults. Therefore, is it appropriate to apply the diagnostic criteria used in adults to pediatric MPN? Is the natural history of pediatric MPN identical to adult MPN? Can the same therapeutic modalities be used in a growing young person? Data on pediatric MPN are limited. They consist primarily of large decentralized meta-analyses and small case reports. Thus, it is possible that this article raises as many questions about the diagnosis of pediatric MPN as it answers.