Characterization of myeloproliferative neoplasms in the paediatric and young adult population

Abstract

Summary The aim of this study was to compare the genomic features and clinical outcomes between paediatric and young adult patients (PAYA, <40 years) and older adults (OA, ≥40 years) with myeloproliferative neoplasms (MPN) to gain insight into pathogenesis, disease prognosis and management. Of 630 MPN patients, 171 (27%) were PAYA with an average age at diagnosis of 31 years. Females were more prevalent in PAYA than OA (71% vs 58%; p = 0.002), and PAYA more frequently presented with essential thrombocytosis (ET) at diagnosis (67% vs 39%; p < 0.001). The presence of a JAK2 somatic mutation was higher in OA (80.4% vs 64.3%; p < 0.001), while a CALR mutation or lack of any traditional driver mutation was more common in PAYA (20.5% vs 10.5%; p = 0.001, 8.8% vs 3.7%; p = 0.01 respectively). Venous thrombosis was more common in PAYA compared to OA (19.8% vs 10.7%; p = 0.002). PAYA had a higher prevalence of familial MPN and familial cancer predisposition, and two PAYA patients harboured pathogenic germline JAK2 lesions. PAYA demonstrated longer survival from diagnosis than OA (median not reached vs 13 years), while disease transformation was less frequent (19.3% vs 37.9%).

Position paper: The time for cooperative group study of ropeginterferon alfa‐2b in young patients with myeloproliferative neoplasms is now

“…9 Splanchnic vein thrombosis is common in this population, and unfortunately, this is often associated with significant morbidity. 8,9 Fibrotic transformation was reported in three of the young cohorts, ranging from 7 to 16% of ET patients and 9 to 24% of PV patients [6][7][8] (Table 1). While transformation to AML occurred much less frequently than in older patients, leukemic transformation was observed with PV.…”

“…Several recent studies reviewed clinical and molecular features of MPNs in adolescent and young adult (AYA) cohorts, including a European consortium detailing a large cohort of MPN patients diagnosed before 25 years old (Table 1). [5][6][7][8] In these publications, AYA patients comprise anywhere from 8 to 27% of total MPN patients. [5][6][7] In all cohorts, including those focused on pediatric patients, ET was the most common MPN type.…”

“…[5][6][7][8] In these publications, AYA patients comprise anywhere from 8 to 27% of total MPN patients. [5][6][7] In all cohorts, including those focused on pediatric patients, ET was the most common MPN type. ET in younger patients was associated with higher rates of "triple negative" status than older cohorts.…”

“…Indeed, the highest rates of triple negative disease occur in younger children and teens. [5][6][7][8] Thrombotic events and fibrotic transformation were frequent complications in young patients. [5][6][7] One cohort reported 24% of PV and TA B L E 1 Summary of recent pediatric and young adult MPN literature.…”

“…Harris et al 7 Szuber et al 6 Boddu et al 5 Sobas et al 6 Another group reported that VTE occurred in 20% of young MPN patients. 7 In the European cohort of patients under 25 years, 11% had a history of thrombosis while an additional 11% developed a new VTE after diagnosis. 8 Our group saw similar rates of thrombosis (12%) in a pediatric cohort in the United States.…”