C097 | MDS/MPN OTHER THAN CMML: AN ITALIAN COOPERATIVE STUDY

Background: MDS/MPN syndromes include chronic myelomonocytic leukemia (CMML), MDS/MPN with neutrophilia or atypical chronic myeloid leukemia (aCML), MDS/MPN neoplasm with SF3B1 mutation and thrombocytosis (-SF3B1) and MDS/MPN not otherwise specified (NOS), not meeting the criteria for a defined category. Molecular and clinical features of MDS/MPN entities other than CMML have been poorly investigated. Methods: Thus, we decided to investigate these MDS/MPN entities collecting demographic, clinical, molecular and outcome data through a Italian nation-wide collaboration, involving several centres belonging to Gruppo Laziale for the study of Ph-negative MPN, Milan, Cremona and Pescara. 68 patients were enrolled (30 MDS/MPN-SF3B1, 10 MDS/MPN with neutrophilia/aCML, 28 MDS/MPN NOS). Results: When comparing the three groups of patients, we found no differences in terms of age and gender, while we observed a higher incidence of anaemia and thrombocytosis in MDS/MPN-SF3B1 cohort (median Hb: 9 g/dl vs 10.1 g/dl and 11 g/dl in aCML and MDS/MPN NOS, respectively; p= 0.0275. Median platelets: 500.000/mcg vs 269.000/mcg vs 190.000/mcg in aCML and MDS/MPN NOS, respectively; p= 0.0041). Furthermore, aCML patients presented higher white blood cell count (median 38.350/mcg vs 6.090/mcg vs 10.850/mcg in MDS/MPN-SF3B1 and MDS/MPN NOS, respectively; p<0.001). No differences were observed in terms of blast percentage in bone marrow. Most of the patients presented normal karyotype (69%). NGS was available for 43 patients (Fig 1A). aCML presented higher median number of mutations (5 vs 2 and 2 in MDS/MPN-SF3B1 and MDS/MPN NOS, respectively; p=0.0445). At a median follow-up of 23.4 months, median overall survival (OS) and leukemia-free survival (LFS) were 108 and 101 months, respectively; aCML presented the worse prognosis [median OS: 14.6 vs 101 months vs not reached in MDS/MPN NOS and MDS/MPN-SF3B1, respectively; p=0.039 (Fig 1B). Median LFS: 14.6 vs 101 months vs not reached in MDS/MPN NOS and MDS/MPN-SF3B1, respectively; p=0.0065]. IPSS-M stratification, performed in 36 patients, correctly predicted both OS (high risk: 14.6 vs 108.5 months in low risk; p<0.0001) and LFS (high risk: 13.4 vs 101 months in low risk; p<0.0001) (Fig 1C). Conclusions: Our analysis confirmed the genomic complexity and dismal outcome of aCML. IPSS-M can efficiently stratify patients’ risk in a real-world setting and may inform on both follow-up timing and therapeutic possibilities.