Refined cytogenetic-risk categorization for overall and leukemia-free survival in primary myelofibrosis: A single center study of 433 patients

We have previously identified sole 9, 13q- or 20q-, as favorable and sole 8 or complex karyotype as unfavorable cytogenetic abnormalities in primary myelofibrosis (PMF). In this study of 433 PMF patients, we describe additional sole abnormalities with favorable (chromosome 1 translocations/duplications) or unfavorable (7/7q-) prognosis and also show that other sole or two abnormalities that do not include i(17q), 5/5q-, 12p-, inv(3) or 11q23 rearrangement are prognostically aligned with normal karyotype, which is prognostically favorable. These findings were incorporated into a refined two-tired cytogenetic-risk stratification: unfavorable and favorable karyotype. The respective 5-year survival rates were 8 and 51% (hazard ratio (HR): 3.1, 95% confidence interval (CI): 2.2-4.3; P0.0001). Multivariable analysis confirmed the International Prognostic Scoring System (IPSS)-independent prognostic value of cytogenetic-risk categorization and also identified thrombocytopenia (platelets 100 × 10⁹ /l) as another independent predictor of inferior survival (P0.0001). A similar multivariable analysis showed that karyotype (P0.001) and platelet count (P0.04), but not IPSS (P0.27), predicted leukemia-free survival; the 5-year leukemic transformation rates for unfavorable versus favorable karyotype were 46 and 7% (HR: 5.5, 95% CI: 2.5-12.0; P0.0001). This study provides the rationale and necessary details for incorporating cytogenetic findings and platelet count in future prognostic models for PMF.