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

Abstract

Myeloproliferative neoplasms (MPN) are uncommon in children/young adults. Here we present data on unselected patients diagnosed before 25 years of age included from 38 centres 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 % pt/year), peri-hepatic vein thromboses were most frequent (47.6% venous events) and logistic regression identified JAK2V617F mutation (p=0.016) and hyperviscosity symptoms (visual disturbances, dizziness, vertigo, headache) as risk factors (p=0.040). New hemorrhagic events occurred in 44 patients (9.9%, 1.04 % pt/y). Disease transformation occurred in 48 patients (10.9%, 1.13 % pt/year), usually to myelofibrosis (7.5%) with splenomegaly as a novel risk factor for transformation in ET (p= 0.000) in logistical regression. Eight deaths (1.8%) were recorded, three after allogeneic stem cell transplantation. Concerning conventional risk scores: IPSET-T and IPSET-NT differentiated ET patients in terms of thrombotic risk. Both scores identified high-risk patients with the same median thrombosis-free survival of 28.5y. No contemporary scores were able to predict survival for young ET or PV 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.

Characterization of myeloproliferative neoplasms in the paediatric and young adult population

“…PAYA with PV were also biased toward females, an unexpected finding of this study. Consistent with prior reports, PAYA differed in their MPN somatic driver lesion profile compared to OA 8,26,27 . Molecular profiling revealed a lower frequency of JAK2 p.V617F mutations in ET and MF compared to OA, with an increase in both CALR exon 9 mutations and TN disease.…”

“…6,7 More recently a large multi-institutional European cohort described 440 MPN patients under the age of 25. 8 These studies confirm that PAYA represent a significant portion of the MPN population, and that their study defines unique presentations and outcomes.…”

“…Two large single‐institution studies identifying MPN patients younger than 40 and 45 years of age observed frequencies of 12% and 8.3% respectively 6,7 . More recently a large multi‐institutional European cohort described 440 MPN patients under the age of 25 8 . These studies confirm that PAYA represent a significant portion of the MPN population, and that their study defines unique presentations and outcomes.…”

“…Consistent with prior reports, PAYA differed in their MPN somatic driver lesion profile compared to OA. 8,26,27 Molecular profiling revealed a lower frequency of JAK2 p.V617F mutations in ET and MF compared to OA, with an increase in both CALR exon 9 mutations and TN disease. Importantly, the frequency of venous thrombosis was found to be higher in PAYA than OA, while presentation with MF was uncommon in PAYA.…”

“…Similar to prior studies, splanchnic thromboses were the most common venous thrombotic events in PAYA. 8,30,31 Thus, the presence of splanchnic thrombosis in a young patient should prompt investigation for a JAK2 mutation.…”