Historically, there has been a lack of understanding around clinical and laboratory features and prognostic factors for children with myeloproliferative neoplasms (MPNs), as MPNs are especially rare in this patient population.
The first known nationally representative survey of Philadelphia-negative myeloproliferative neoplasms (MPNs) is offering more data about the clinical features of the group of clonal hematopoietic disorders in pediatric patients.
Based on the findings, the researchers point to considerable differences between adult and pediatric MPNs, which they say warrant specialized diagnostic criteria and clinical management standards for children with Philadelphia-negative MPNs.
Historically, there has been a lack of understanding around clinical and laboratory features and prognostic factors for children with MPNs, as MPNs are especially rare in this patient population.
“Although hematologic findings are similar between cases of adult and pediatric MPNs in terms of clinical findings and genetic events, considerable differences have been indicated by several studies,” noted the researchers of the survey. According to the researchers, who offered an example: “Recently, three driver mutations in JAK2, CALR, and MPL were incorporated into the diagnostic criteria, but the prevalence of these mutations in pediatric patients is reported to be much lower than that in adults. Consequently, the diagnosis of childhood MPN often relies on clinical and laboratory findings in combination with the exclusion of secondary thrombosis, rather than using molecular markers.”
Addressing this gap, the researchers compiled data on more than 50 children diagnosed with an MPN between 2000 and 2016 were compiled.
Of these patients, 44 had essential thrombocythemia (ET), 4 had polycythemia vera (PV), and 1 had primary myelofibrosis. The median age of the patients were 14, 9, and 0 years, respectively, and the male to female ratio was 4:1, 21:23, and 1:0, respectively.
“The frequency of complications, such as thrombosis, hemorrhage, transformation to myelofibrosis, and development of leukemia, was much lower in our evaluated pediatric patients than in adult patients,” explained the researchers, who found that no patients with PV experienced an event. There were 4 patients with ET who experienced hemorrhage and 3 patients with ET who experiencedthrombotic events.
Notably, 2 patients developed myelofibrosis and subsequent acute myeloid leukemia (AML); the researchers noted that both patients were relatively old for the study cohort. One of these patients had PV, and her initial leukocyte count and abnormal karyotype were considered to be risk factors for developing leukemia. She was the only patient in the cohort who had an abnormal karyotype. Prior research has shown that the incidence of transformation to myelofibrosis and/or leukemia is significantly higher in adult patients.
All patients with PV were negative for the JAK2 V617F variant and 1 patient had a family history of erythrocytosis. The variant was detected in 9 of the 39 tested patients with ET. There were 12 patients with ET tested for the CALR mutation, 1 of which tested positive. There were also 15 patients with ET tested for the MPL variant, although none were positive.
Blood analyses showed that:
Ishida H, Miyajima Y, Hyakuna N, et al. Clinical features of children with polycythemia vera, essential thrombocythemia, and primary myelofibrosis in Japan: a retrospective nationwide survey. Br J Haematol. Published online June 27, 2020. doi: 10.1002/jha2.39.