PS1458 RISK FACTORS AND OUTCOME OF ACUTE MYELOID LEUKEMIA SECONDARY TO POST-POLYCYTHEMIA VERA AND POST-ESSENTIAL THROMBOCYTHEMIA MYELOFIBROSIS: AN ANALYSIS OF THE MYSEC COHORT
Authors: B. Mora, P. Guglielmelli, E. Rumi, M. Maffioli, D. Barraco, A. Rambaldi, M. Caramella, R. Komrokji, J.J. Kiladjian, J. Gotlib, A. Iurlo, F. Cervantes, T. Devos, F. Palandri, V. De Stefano, M. Ruggeri, R.T. Silver, G. Benevolo, F. Albano, C. Cavalloni, D. Pietra, T. Barbui, G. Rotunno, L. Bertù, M. Cazzola, A.M. Vannucchi, F. Passamonti
Journal: HemaSphere (2019)

Background: Information on the molecular and phenotypic correlates of acute myeloid leukemia secondary (S-AML) to post-polycythemia vera (post-PV) and post-essential thrombocythemia (post-ET) myelofibrosis (known as secondary myelofibrosis, SMF) is scant. Aims: The primary objective of this study is to assess the incidence and outcome of S-AML in a large cohort of SMF. To find out predictors of S-AML occurrence, we performed a whole investigation of risk factors at the time of SMF, also applying established prognostic models. Methods: The MYSEC (Myelofibrosis Secondary to PV and ET Collaboration) project was recently updated collecting 805 SMF cases. We performed time-to-event (S-AML) analysis with Fine & Gray competing risks model using either death or the time of stem cell transplantation as competing risks. To explore whether IPSS (International Prognostic Scoring System), DIPSS (Dynamic IPSS) and MYSEC-PM (MYSEC-Prognostic Model) predicted S-AML occurrence, we calculated the difference in Cumulative Incidence Function (CIF) among risk categories for each score and applied Gray's model for testing the homogeneity of CIFs. Results: Within 805 SMF patients, 71 (8.8%) developed S-AML. Median time from SMF to S-AML evolution was 1.6 years (range: 0.6 - 14.6). The S-AML incidence rate was 2.3 x100 person-year of follow up (CI 95%: 1.8 - 2.9 x100). In univariate analysis, we found a direct association between increased S-AML risk and platelets <150 x10^9/l, hemoglobin <10 g/dl, PV/ET duration > 14 years, blasts ≥ 3% and non-CALR genotype, and an inverse association with the use of JAK2 inhibitors. In a multivariate analysis, only blasts ≥ 3%, PV/ET duration > 14 years and non-CALR genotype maintained their association with an increased risk of S-AML (Table 1). No impact on S-AML risk was found as for leukocyte count, spleen size, symptoms, karyotype and age at SMF; neither imbalance was evident for gender, previous PV versus ET, and cytoreduction.Among IPSS, DIPSS and MYSEC-PM, only the latter score stratified SMF patients for S-AML risk (P = 0.004) (Figure 1a). The estimated hazard ratios (HRs) when changing score category were: 1.55 (CI 95%: 0.69 - 3.50) from low to intermediate-1, 1.09 (CI 95%: 0.51 - 2.34) from intermediate-1 to intermediate-2, and 2.42 (CI 95%: 1.01 - 5.77) from intermediate-2 to high risk. Comparing to lower risk groups, HR for high risk cases was 4.07 (CI 95%: 1.66 - 10.03). Among S-AML, 65 (91.5%) patients died and the median survival was 3.9 months (CI 95%: 2.4 - 6.8) (Figure 1b).Summary/Conclusion: In our dataset of 805 SMF patients, ∼ 9% evolved into S-AML. The S-AML incidence rate was 2.3 x100 person-year and the median survival dismal. In a multivariate analysis, blasts ≥ 3%, non-CALR genotype and longer duration of PV/ET correlated with an increased risk of S-AML. Besides, our data supports the relevance of MYSEC-PM in predicting S-AML evolution, especially for the opposite categories of low and high risks.