Gangat, Naseema

Abstract In an international collaborative study, a central histologic review identified 891 patients with essential thrombocythemia, strictly defined by World Health Organization criteria. After a median follow-up of 6.2 years, 109 (12%) patients experienced arterial (n = 79) or venous (n = 37) thrombosis. In multivariable analysis, predictors of arterial thrombosis included age more than 60 years (P = .03; hazard ratio [HR] = 1.7), thrombosis history (P = .003; HR = 2.1), cardiovascular risk factors including tobacco use, hypertension, or diabetes mellitus (P = .007; HR = 1.9), leukocytosis (> 11 × 109/L; P = .04; HR = 1.7), and presence of JAK2V617F (P = .009; HR = 2.6). In contrast, only male gender predicted venous thrombosis. Platelet count more than 1000 × 109/L was associated with a lower risk of arterial thrombosis (P = .007; HR = 0.4). These associations, except the one with leukocytosis, remained significant (or near significant) when analysis was restricted to JAK2V617F-positive cases. The current study clarifies the contribution of specific disease and host characteristics to the risk of arterial versus venous thrombosis in essential thrombocythemia.

Abstract Survival in cytogenetically high-risk patients with acute myeloid leukemia or myelodysplastic syndromes is significantly worse in the presence of a monosomal karyotype (MK). The objective of the present study was to determine whether the same held true for primary myelofibrosis. Among 793 primary myelofibrosis patients seen at our institution, 62 displayed an unfavorable karyotype by way of complex karyotype (n = 41) or sole trisomy 8 (n = 21). Seventeen (41%) of the 41 patients with complex karyotype were classified as having an MK. Median survival was 6, 24, and 20 months in patients with MK, complex karyotype without monosomies, and sole trisomy 8, respectively (P < .0001). The corresponding 2-year leukemic transformation rates were 29.4%, 8.3%, and 0 (P < .0001); hazard ratios (95% confidence intervals) were 6.9 (1.3-37.3) and 14.8 (1.7-130.8). The prognostic relevance of MK was not accounted for by the Dynamic International Prognostic Scoring System. We conclude that MK in primary myelofibrosis is associated with extremely poor overall and leukemia-free survival.

Purpose The Dynamic International Prognostic Scoring System (DIPSS) for primary myelofibrosis (PMF) uses five risk factors to predict survival: age older than 65 years, hemoglobin lower than 10 g/dL, leukocytes higher than 25 × 10 9 /L, circulating blasts ≥ 1%, and constitutional symptoms. The main objective of this study was to refine DIPSS by incorporating prognostic information from karyotype, platelet count, and transfusion status. Patients and Methods Mayo Clinic databases for PMF were used to identify patients with available bone marrow histologic and cytogenetic information. Results Seven hundred ninety-three consecutive patients were selected and divided into two groups based on whether or not their referral occurred within (n = 428; training set) or after (n = 365; test set) 1 year of diagnosis. Multivariable analysis identified DIPSS, unfavorable karyotype, platelets lower than 100 × 10 9 /L, and transfusion need as independent predictors of inferior survival. Hazard ratio (HR) –weighted adverse points were assigned to these variables to develop a composite prognostic model using the training set. The model was subsequently validated in the test set, and its application to all 793 patients resulted in median survivals of 185, 78, 35, and 16 months for low, intermediate-1 (HR, 2.2; 95% CI, 1.4 to 3.6), intermediate-2 (HR, 4.9; 95% CI, 3.2 to 7.7), and high-risk groups (HR, 10.7; 95% CI, 6.8 to 16.9), respectively (P < .001). Leukemia-free survival was predicted by the presence of thrombocytopenia or unfavorable karyotype (10-year risk of 31% v 12%; HR, 3.3; 95% CI, 1.9 to 5.6). Conclusion DIPSS plus effectively combines prognostic information from DIPSS, karyotype, platelet count, and transfusion status to predict overall survival in PMF. In addition, unfavorable karyotype or thrombocytopenia predicts inferior leukemia-free survival.