MPN-244: Comorbid Conditions Occur Frequently and Correlate with Early Disease Progression and Poor Outcomes in Young Patients with Myelofibrosis

Context: Myelofibrosis (MF) rarely presents in young patients. Young patients with MF enjoy a more indolent disease course and a lower incidence of adversely prognostic clinical and genomic variables. Analysis of this population may identify patient-specific variables that predict for early disease onset or progression, as well as keys to myeloproliferative neoplasm pathogenesis, specifically with regard to inflammation. Design: We analyzed MF patients ≤ 50 years at diagnosis. Comorbid conditions present at diagnosis were classified by etiology. DIPSS score (range 0–5) was calculated from clinical variables (except age) at initial presentation and 3 and/or 5 years later, when available. Change in DIPSS represented a surrogate for clinical disease progression. Results: Among 63 patients, the median age was 43.6 years. Twenty-four (38%) were men. Forty-six (73%) had primary MF, while 17 (27%) had secondary MF. At first presentation, 18 (29%), 28 (44%), 14 (22%), and 2 (3%) had low-, int-1-, int-2-, and high-risk disease by DIPSS, respectively. With a median follow-up of 55 and 95 months from presentation and diagnosis, respectively, median OS was not reached. Among 58 patients with a known reason for presentation, 36 (62%) presented due to incidental lab abnormalities, and 17 (29%) presented with symptomatic disease (symptomatic cytopenias, splenomegaly, constitutional symptoms, thrombosis), with symptomatic cytopenias being most common (n = 9; 16%). Among 31 (49%) with comorbidities accompanying/predating diagnosis, 5 (8%) were infectious, 10 (16%) autoimmune, 10 (16%) inflammatory, 12 (19%) cardiovascular/metabolic, and 1 (2%) malignant. Six had more than one class of comorbidity. Twenty-six patients had clinical data sufficient to calculate a DIPSS score at 3 and/or 5 years after presentation. Nine (35%), 8 (31%), and 9 (35%) had a decrease, no change, and increase in DIPSS, respectively. Increasing DIPSS correlated with a worse OS (p=0.05) and the presence of comorbidity (p=0.02). Conclusions: In young MF patients, comorbid conditions are common and correlate with an increased risk of disease progression, which, in turn, correlates with poor survival. This supports the role of inflammation in disease initiation and progression and identifies potential therapeutic avenues to delay disease progression and/or identify patients at high risk of progression. No grant funding was used for this study.