Young platelet millionaires with essential thrombocythemia

The platelet count threshold for World Health Organization classification system-compliant diagnosis of essential thrombocythemia (ET) is ?450 × 109/L.1 Extreme thrombocytosis (ExT), on the other hand, arbitrarily defined by ?1000 109/L and occurs in approximately 22% patients with ET, at time diagnosis.2 Note, ExT most frequent context young ET incidence rates 44%/29%/29% aged ?40, 41–60, > 60 years respectively.3 presence has been shown to confer a lower risk arterial thrombosis4; additionally, its association hemorrhage linked aspirin use.5 Nevertheless, often poses therapeutic dilemma low-risk terms need cytoreductive therapy, stemming from an unsubstantiated concern heightened thrombotic risk, or ameliorate bleeding tendency microvascular symptoms. In light inadequate published literature we compiled this report specifically focusing patients. Our main objectives were (a) characterize clinical phenotype “young” millionaires via comparison their counterparts without (b) assess long term outlook thrombosis, myelofibrotic/leukemic transformation overall survival. Study retrospectively recruited Mayo Clinic myeloproliferative neoplasms (MPN) database which maintained under institutional review board approved protocol included 3023 MPN evaluated over five decades (1967 through 2017).2 Of 1070 adult ET; 192 (18%) below 40 years. Major thrombosis myocardial infarction, angina, cerebrovascular accidents, transient ischemic attack, peripheral aortic mesenteric artery central retinal thrombosis. venous deep pulmonary embolism, portal/splenic/mesenteric/hepatic vein cerebral sinus Bleeding events that required red cell transfusions classified as major hemorrhage. Follow up each patient was updated December 2020 means either phone call electronic communication referring physician. Conventional statistical methods utilized using JMP Pro 14.0.0 software package, SAS Institute, Cary, NC Cox proportional hazards model multivariable analyses Kaplan-Meir estimator overall, leukemia-free, myelofibrosis-free thrombosis-free Median age our study cohort (n = 192) 31 (range; 18–39) female preponderance (70%). Half 96) presented ExT. order accurately define ExT, compared laboratory features (Table S1). Young frequently harbored CALR mutation (46% vs 25%) opposed JAK2 (35% 56%; P .05), also higher leukocyte (median 9.5 7.8 109/L; .03). prior significantly amongst (2% 8%; .04). On prevalence cardiovascular factors similar those Despite these findings, much proportion received initial agents mainly hydroxyurea anagrelide (64% 47%; .04) suggested differences individual physician discretion. As expected, trend towards rate before after observed (15% 7%, .09) might be accounted acquired Von Willibrand's syndrome (AvWS) 8/15 (53%) 4/13 (31%; .23) Interestingly, symptoms (18% 22%, .55). All followed median 16 2–51 years); total 34 deaths recorded; 25 occurred who note, international prognostic score survival (IPSET) categories (P .86). age-adjusted analysis, emerged independent predictor shortened (HR, 2.32. 95% CI, 1.1–4.99; .02; Table S2). Figure 1(A) highlights difference beyond three decades, Leukemic fibrotic transformations recorded thirty-two respectively. leukemic 27.5 20.1–36.6 years). It noted two directly transformed acute leukemia development myelofibrosis; mutated, mutated; next generation sequencing (NGS) panel obtained one did not harbor high mutations; karyotype available four only abnormal del (20q). No leukemogenic therapies administered specific limited 4), 3) interferon 2). case survival, leukemia-free .01, S2; 1(B)). .98; 1(C)). mutational analysis performed subset 53), spliceosome, P53 mutations.6 Moreover, mutations detected DNMT3A 2) RUNX1 1). diagnosis, (17 23%), primarily (9% 15%) (8% 10%). all relevant variables known impact namely age, leukocytosis ?11 109/L, gender, driver mutations, factors, along latter borderline significant, conferring reduced .14, HR 0.62; S2, 1(D)). current defines distinct salient genotypic phenotypic characteristics. Both are consistent mostly status.7 exceedingly follow spans enabled us appreciate long-term spite progression. This previous work implicating factor progression ET.8 These observations warrant further investigation, suggest underlying biological underscore importance delineate natural history. Importantly, counseling should provided regarding obviating counts therapy low asymptomatic Naseema Gangat Ayalew Tefferi designed study, collected data, wrote paper. Natasha Szuber Tabinda Jawaid analyzed data. Curtis A. Hanson reviewed bone marrow morphology. Animesh Pardanani authors final draft None. S1 Clinical characteristics (age < stratified absence extreme (? 1000 109/L) S2 Univariate (ET). Please note: publisher responsible content functionality any supporting information supplied authors. Any queries (other than missing content) directed corresponding author article.