Clinical features, management, and outcomes of adolescents and young adults with myeloproliferative neoplasms.

Abstract

6580 Background: Myeloproliferative neoplasms (MPNs)—polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis (MF)—are chronic myeloid malignancies mainly occurring in older adults. However, up to 20% of pts are diagnosed as adolescents and young adults (AYA; ages 13–39). Thus, treatment guidelines and outcome data primarily apply to older subjects, leaving clinical features, outcomes, and management of younger pts poorly defined. We describe the characteristics, risk stratification, and treatment of AYA pts at a tertiary academic center. Methods: We conducted a retrospective study of AYA pts with MPN treated at Mass General Brigham between 2007–2025. Pts diagnosed at ages 13–39 and meeting 2022 WHO criteria for MPN were included. Data abstracted from the electronic medical record included demographics, diagnostics, cardiovascular (CV) risk factors, thrombotic and bleeding events, risk stratification, and management. Descriptive statistics were applied. Results: 90 AYA pts with MPN were identified. Median age at diagnosis was 27 years (range 16–39), 53 (58.9%) were female and 64 (71.1%) were White. ET was the most frequent (65.6%), followed by PV (22.2%), MF (6.7%), and MPN-unclassified (5.6%). Most pts (73.3%) were diagnosed incidentally with abnormal blood counts. At least one CV risk factor—HTN, HL, DM, BMI >25, tobacco use—was present in 53 pts (58.9%). JAK2 mutation was present in 55 pts (61.1%), CALR in 26 (28.9%), MPL in 3 (3.3%), and triple-negative in 7 (7.8%). Across 18 (20.0%) pts, 23 thrombotic events occurred; arterial (n= 9) and venous (n= 14);13 in the year prior to diagnosis and 10 after; 3 pts (3.3%) experienced events in both time periods and 4 (4.4%) pts experienced more than one event. Seven (7.8%) experienced major bleeding in the year prior to diagnosis or any time after, defined by ISTH criteria. Of the 23 pts with thrombotic and/or bleeding events, 19 were subsequently cytoreduced, most often with interferon (ropeginterferon n=10; peginterferon n=3). One pt received ruxolitinib and 12 hydroxyurea. Of 71 pts classified as low-risk, 34 (47.9%) received cytoreduction. Indications included extreme thrombocytosis (32.4%), inadequate control with phlebotomy (23.5%), symptom burden (23.5%), bleeding risk/history (17.6%), and disease modification (14.7%). Median follow-up was 3.6 years (IQR 1.9-7.6), 4 (4.4%) pts progressed to MF, and 1 (1.1%) to accelerated phase MPN. Two (2.2%) of these pts have undergone allogeneic stem cell transplantation. One (1.1%) death was reported during follow-up. Conclusions: In this AYA MPN cohort, > 20% were high-risk due to thrombotic events. CV comorbidities were common despite young age. Nearly half of low-risk pts received cytoreductive therapy, highlighting potential limitations of standard risk stratification in young pts. These findings support the need for age-specific guidelines for AYA pts with MPN.