Adolescent and Young Adult versus Older Adult Philadelphia-Negative Myeloproliferative Neoplasms: A Single-Center Experience from the MENA Region.

BACKGROUND: Philadelphia-negative myeloproliferative neoplasms (MPNs), including essential thrombocythaemia (ET), polycythaemia vera (PV), and myelofibrosis (MF), usually affect older adults, but a subset occurs in adolescents and young adults (AYA). Regional age-stratified data remain limited. METHODS: We retrospectively studied Philadelphia-negative MPN patients managed at the National Center for Cancer Care and Research from 2014 to 2024. Patients were classified as AYA (15-39 years) or older adults (≥40 years). Clinical, laboratory, molecular, thrombotic, bleeding, transformation, and survival outcomes were analyzed by subtype. Risk categories followed institutional disease-specific practice; analyses were descriptive and unadjusted. RESULTS: The cohort included 220 patients: 79 ET, 47 MF, and 94 PV; 76 (34.5%) were AYA. Low-risk disease predominated in AYA ET (p<0.001) and PV (72.4% vs 35.4%; p=0.002), partly reflecting age-based risk definitions. In ET (molecular n=30 vs 49), CALR was 16/30 (53.3%) versus 19/49 (38.8%) and JAK2 was 6/30 (20.0%) versus 21/49 (42.9%); MPL, triple-negative, and unavailable categories were 2, 4, and 2 versus 2, 6, and 1, respectively. In MF (n=11 vs 36), JAK2 was 4 (36.4%) versus 18 (50.0%), CALR 4 (36.4%) versus 10 (27.8%), MPL 0 versus 2 (5.6%), triple-negative 1 (9.1%) versus 3 (8.3%), and unavailable data 2 (18.2%) versus 3 (8.3%). In PV (n=29 vs 65), JAK2 V617F was 28 (96.6%) versus 63 (96.9%) and JAK2 exon 12 was 1 (3.4%) versus 2 (3.1%). Overall survival did not differ by age. CONCLUSION: AYA patients with Philadelphia-negative MPNs demonstrated age-related differences in risk classification, molecular profile, and thrombotic phenotype, while overall survival was comparable to older adults. Larger prospective multicenter studies are warranted.