Characterization of myeloproliferative neoplasms in the paediatric and young adult population

Area of Science:

• Hematology
• Genetics
• Oncology

Background:

• Myeloproliferative neoplasms (MPN) are a group of clonal hematopoietic stem cell disorders.
• Understanding age-related differences in MPN is crucial for personalized treatment strategies.
• Previous studies have not fully elucidated the distinct genomic and clinical features between younger and older MPN patient cohorts.

Purpose of the Study:

• To compare genomic features and clinical outcomes of paediatric and young adult patients (PAYA, <40 years) versus older adults (OA, ≥40 years) with MPN.
• To investigate potential differences in MPN pathogenesis, prognosis, and management based on age.

Main Methods:

• Retrospective analysis of 630 MPN patients, categorizing them into PAYA (<40 years) and OA (≥40 years) groups.
• Comparison of demographic data, clinical presentation (including essential thrombocytosis and venous thrombosis), somatic and germline mutation status (JAK2, CALR, etc.), familial MPN prevalence, and disease outcomes (survival, transformation).

Main Results:

• PAYA patients (27% of cohort) were younger at diagnosis (avg. 31 years), more frequently female (71%), and presented more often with essential thrombocytosis (67%).
• OA patients had higher JAK2 mutation rates (80.4%), while PAYA patients showed more CALR mutations (20.5%) or lacked traditional driver mutations (8.8%).
• PAYA patients experienced higher rates of venous thrombosis (19.8%) but demonstrated significantly longer survival (median not reached vs. 13 years) and less disease transformation (19.3% vs. 37.9%).

Conclusions:

• Significant differences exist in genomic profiles and clinical outcomes between PAYA and OA with MPN.
• PAYA patients exhibit distinct genetic drivers and a more favorable prognostic profile compared to OA.
• These findings underscore the need for age-specific approaches in MPN diagnosis, risk stratification, and therapeutic management.