Cytogenetic abnormalities in polycythemia vera: phenotypic correlates and prognostic relevance in 669 informative cases

Abstract

The main objective of the current study was to provide a detailed account on the prognostic relevance of abnormal karyotype (AK) and associated specific cytogenetic abnormalities in polycythemia vera (PV). 669 PV patients were informative, of which 436 (65%) were evaluated within 1 year of diagnosis. Karyotype was abnormal in 67 (15%) patients, including isolated abnormalities of loss of Y chromosome (-Y; N=15; 3%), +9 (N=11; 3%), del(20q) (N=10; 2%), +8 (N=4; 1%). AK correlated with older age (p<0.01), lower platelet count (p<0.01), and grade ≥2 reticulin fibrosis (p<0.01). Specifically, del(20q) correlated with older age and grade ≥2 reticulin fibrosis; +9 with higher incidence of venous thrombosis history. SRSF2 and IDH2 mutations clustered with normal karyotype. At a median follow-up of 7.4 years, 163 (37%) deaths, 50 (11%) fibrotic (post-PV MF) and 14 (3%) leukemic transformations (LT) were documented. In univariate analysis, AK was associated with inferior overall survival (median 10.5 vs 16.3 years; p<0.01); significance was sustained during multivariable analysis (HR 2.0; p=0.02), along with age ≥60 years (p<0.01), leukocytosis ≥15 × 109/L (p<0.01) and SRSF2 (p<0.01) mutation. AK was also associated with post-PV MF (21% vs 10%; p<0.01) and LT (7% vs. 2%; p<0.01); significance was sustained during multivariable analysis for post-PV MF (HR 3.7; p<0.01, but not LT (P=0.47). In regard to specific abnormalities, del(20q) was associated with progression to post-PV MF and ≥2 abnormalities with LT. The current study describes the spectrum of cytogenetic abnormalities in PV and their associated phenotypic and prognostic correlates.