Abnormal Karyotype and Prognosis in Polycythemia Vera: A Single Center Experience in 239 Informative Cases

Abstract Background In polycythemia vera (PV), abnormal karyotype at diagnosis has been reported in 10% to 20% of patients and some studies have suggested an association with inferior survival (Leukemia 2013;27:1874) . In the current study, we examined the prognostic contribution of abnormal karyotype, in general, and specific abnormalities, in particular, in newly diagnosed PV. Methods Study patients were selected from our institutional database of myeloproliferative neoplasms (MPN) and fulfilled the 2008 World Health Organization (WHO) criteria for diagnosis of PV (Blood. 2009;114:937). Cytogenetic analysis and reporting was done according to the International System for Human Cytogenetic Nomenclature (Cytogenetic and Genome Research 2013;141:1-6). Assignment as "unfavorable karyotype" was according to criteria established for PMF: favorable = normal + favorable abnormalities; unfavorable = unfavorable abnormalities (Leukemia. 2011;25:82). Screening for the two most frequent mutations in PV, other than JAK2 (i.e. TET2 and ASXL1), were performed according to conventional methods (Leukemia. 2014;28:2206). Statistical analyses considered clinical and laboratory parameters obtained at time of diagnosis. Results Patient characteristics: Median (range) values for the 239 study patients (53% females) included: age 62 (17-94), leukocyte count 11.7 x 10(9)/L (4.3-59.3) and platelet count 479 x 10(9)/L (37-2747). Palpable splenomegaly was present in 26% of the patients, pruritus in 27%, erythromelalgia in in 8%, hypertension in 47%, diabetes in 10% and hyperlipidemia in 28%. Thrombosis history at diagnosis was documented in 33% of the patients and 20% experienced the same after diagnosis. 73% of the patients were "high risk" by conventional risk stratification. Mutation screening for TET2 and ASXL1 was performed in 80 patients and mutational frequencies were 19% and 11% respectively. All study patients provided cytogenetic information, which was abnormal in 46 (19%) patients. The most frequent abnormalities were isolated +9 (n=11; 24% of abnormal karyotype and considered favorable), isolated del(20q) (n=8; 17% of abnormal karyotype and considered favorable), isolated loss of Y chromosome (n=7; 15% of abnormal karyotype and considered favorable) and isolated +8 (n=5; 11% of abnormal karyotype and considered unfavorable). A total of 9 (20% of abnormal karyotype) patients displayed unfavorable karyotype that included +8 in 7 patients, del(11q) in one patient and +20 in one patient. After a median follow-up of 83 months, 70 (29%) deaths, 48 (20%) thrombotic events, 20 (8%) fibrotic progressions and 7 (3%) leukemic transformations were documented. Comparison of patients with and without cytogenetic abnormalities Patients with abnormal cytogenetics were older (p=0.048), displayed lower platelet count (p=0.005) and were more likely to be high risk (p=0.02); there was no significant correlation with TET2 or ASXL1 mutation. In univariate analysis, patients with abnormal cytogenetics displayed inferior leukemia-free (p=0.007; HR 10.6, 95% CI 1.9-58.7), myelofibrosis-free (p Conclusions Cytogenetic abnormalities in PV confer an independent adverse prognostic effect on overall, leukemia-free and myelofibrosis-free survival, but not thrombosis-free survival; the adverse effect on leukemia-free and myelofibrosis-free survival was seen with both favorable and unfavorable cytogenetic abnormalities. Disclosures No relevant conflicts of interest to declare.