CLINICAL, CYTOGENETIC AND MOLECULAR CHARACTERIZATION OF BRAZILIAN COHORT PATIENTS WITH PRIMERY MYELOFIBROSIS AND MYELOFIBROSIS POST-POLYCYTTHEMIA VERA AND POST-ESSENTIAL THROMBOCYTHEMIA

Abstract

Myelofibrosis (MF) is the most severe myeloproliferative neoplasia (MPN), with a very variable survival, which can be beyond 20 years to less than two years. The only curative treatment is allogeneic bone marrow transplantation (ABMT), but this is restricted to patients of less advanced age and is associated with significant mortality and disease relapse. Adequate prognostic characterization is essential for therapeutic decision-making, and modern prognostic indexes using molecular and cytogenetic data have been replacing the traditional indexes. Clinical and laboratory data were evaluated, bone marrow and peripheral blood karyotype were studied, and BCR-ABL1, JAK2, CALR, MPL, ASXL1, SRSF2, EZH2, IDH1, IDH2, U2AF1 mutations were investigated. The classic IPSS, DIPSS, DIPSS plus, and the most recent MIPSS70, MIPSS70 plus, MIPSS 70 plus 2.0, GIPSS, and MYSEC-PM indexes were applied to a population of 230 patients from 8 Brazilian institutions with primary myelofibrosis (MFP) and secondary myelofibrosis polycythemia vera (PV-MF) and essential thrombocythemia (TE-MF) and compared among themselves. The median-age was 65 years-old, the overall survival was 8.1 years (CI 95%, 7,2 – 10,7), with a 5 years estimated survival of 61% (53 – 70). Comparing the prognostic indexes with each other identified a greater accuracy of the prognostic indexes that use mutational and cytogenetic data on the classic prognostic indexes. In the univariate analysis, advanced age, male gender, spleen size, hemoglobin, white blood cell count, peripheral blood blast percentage, SRSF2 mutation, triple-negative patients, IPSS, DIPSS and DIPSS plus stratification, MIPSS70 high risk and MIPSS70 plus high and very high risk showed impact in survival. In the multivariate analysis, triple-negative for JAK2 V617F, CARL , and MPL (p = 0,002) and stratification by IPSS (p < 0,0001) maintained significance as risk factors for overall survival. The present study is the most extensive Brazilian cohort study of patients with MF evaluating these variables.