Real-world study of children and young adults with myeloproliferative neoplasms: identifying risks and unmet needs

Abstract

Myeloproliferative neoplasms (MPNs) are uncommon in children/young adults. Here, we present data on unselected patients diagnosed before 25 years of age included from 38 centers in 15 countries. Sequential patients were included. We identified 444 patients, with median follow-up 9.7 years (0-47.8). Forty-nine (11.1%) had a history of thrombosis at diagnosis, 49 new thrombotic events were recorded (1.16% patient per year [pt/y]), perihepatic vein thromboses were most frequent (47.6% venous events), and logistic regression identified JAK2V617F mutation (P = .016) and hyperviscosity symptoms (visual disturbances, dizziness, vertigo, headache) as risk factors (P = .040). New hemorrhagic events occurred in 44 patients (9.9%, 1.04% pt/y). Disease transformation occurred in 48 patients (10.9%, 1.13% pt/y), usually to myelofibrosis (7.5%) with splenomegaly as a novel risk factor for transformation in essential thrombocythemia (ET) (P= .000) in logistical regression. Eight deaths (1.8%) were recorded, 3 after allogeneic stem cell transplantation. Concerning conventional risk scores: International Prognostic Score for Essential Thrombocythemia-Thrombosis and new International Prognostic Score for Essential Thrombocythemia-Thrombosis differentiated ET patients in terms of thrombotic risk. Both scores identified high-risk patients with the same median thrombosis-free survival of 28.5 years. No contemporary scores were able to predict survival for young ET or polycythemia vera patients. Our data represents the largest real-world study of MPN patients age < 25 years at diagnosis. Rates of thrombotic events and transformation were higher than expected compared with the previous literature. Our study provides new and reliable information as a basis for prospective studies, trials, and development of harmonized international guidelines for the specific management of young patients with MPN.

Graphical abstract

Figure 1.

Driver mutation status in the population of children, adolescents, and young adults. (A) Driver mutation status depending on MPN subtype in the global population. (B) Driver mutations observed in the ET population depending on age. (C) JAK2V617F allele burden at diagnosis of MPN. 3NEG, triple negative; CALR, calreticulin; JAK2, just another kinase 2; Others, MPL or unknown.

Figure 2.

Distribution of cytoreductive drug used as first, second, or third line. SCT, stem cell transplantation.

Figure 3.

Kaplan-Meier curves of complications during follow-up of the global cohort. Thrombosis-free survival curves in all MPN (A) and in the ET population (B). Hemorrhage-free survival curves in all MPN (C) and in the ET population (D). Evolution-free survival curves (E) and overall survival curves (F). 3NEG, triple negative; NR, not reached; O, other MPNs.

Figure 4.

Kaplan-Meier curves for thrombosis and survival scores applied to children, adolescents, and young adults’ population. Survival and thrombosis scores: (A) ELN score and thrombosis, (B) IPSET-T score, (C) IPSET-NT score, (D) ELN score and survival, (E) IPSET survival score, and (F) PV survival score. H, high risk; I, intermediate risk; L, low risk.