Limited Prognostic Value of ELN Classification and Relevance of Molecular Ontogeny in Acute Myeloid Leukemia post Myeloproliferative Neoplasms: A Retrospective Multicenter Study.

Acute myeloid leukemia (AML) post myeloproliferative neoplasm (MPN) have very poor prognosis and are often excluded from most clinical trials. We retrospectively collected data from 166 patients, including 156 with available treatment data and 83 with NGS data treated in France and USA. 2022 ELN risk categories were favorable, intermediate and adverse in 3 (2%), 17 (13%), and 110 (85%), respectively. Overall response rate was 57%, 20%, and 25% in patients treated by intensive chemotherapy (IC), hypomethylating agents (HMAs) and BSC (including low-intensity treatments as hydroxyurea and low-dose cytarabine), respectively. A total of 31 (22%) patients underwent allogeneic stem cell transplantation (ASCT). Median overall survival (OS) was 7.2 months without significant difference between IC and HMA (9.5 and 8.6 months, respectively). OS was significantly improved in patients allografted (6.7 vs. 1.3 months, respectively, p < 0.001). Even though 2017 and 2022 ELN risk categories were not prognostic for OS, we observed a prognostic impact on OS of Lindsley's classifier (p = 0.014). In multivariate analysis, JAK2 mutation was associated with worse OS (p = 0.037), whereas SRSF2 showed a trend toward adverse prognosis (p = 0.057). Among functional groups, only spliceosome mutations predicted poor prognosis (p = 0.015). We confirmed poor prognosis of AML post-MPN. Classical prognostic classification was not validated in our cohort. We observed poor outcome using IC or HMA encouraging us to propose new clinical trials in this specific subgroup. Only ASCT was able to improve prognosis.