MDS-255 Clinical Characteristics and Mutational Profile of Patients With Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia.

Abstract

Next-generation sequencing (NGS) is a booming tool that allows the detection of useful characteristics for the diagnosis and prognosis of myeloid pathologies. An association between certain mutations and clinical characteristics has recently been proposed and predictive models of survival that contribute to the IPSS-R and cytogenetic risk have emerged. To describe clinical characteristics and their association with mutational profiles in patients with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) diagnosis. Assess the usefulness of molecular scales to predict risk and survival. Retrospective cohort study, including adult patients diagnosed with MDS and LMMC from two highly complex private centers. 55 patients were included, 41% women, with a median age of 55 years (31-87). According to the WHO classification, 3 CMML; 27 MDS-DM; 6 MDS-DU; 6 MDS-EB-1; 2 MDS-EB-2, and 1 MDS-SA. Karyotype abnormalities were found in 16 patients (29%), being the alterations in chromosome 8 (8/55), 7 (7/55), and 5 (6/55) the most frequent. 71% (39/55) were classified as good prognosis in the reviewed cytogenetic risk group. According to the IPSS-R, they presented very low risk (20%), low (46%), intermediate (13%), high (7%), and very high (13%). 91% of the patients presented at least one somatic mutation by NGS. The median number of mutations was 3 (0-6). TET2, SRSF2, DNMT3A, ASXL1, and TP53 were the most frequently reported mutations, in 15, 13, 11, 10, and 8 patients respectively. Adverse Risk mutations were found in more than 50% (21/39) of patients with good cytogenetic risk. Of the 36 low/very low-risk patients according to IPSS-R 4/36 (11%) and 6/36 (17%) were categorized as high- and intermediate-risk, respectively, with the MIPSS-Scale. Patients with TET/IDH mutations had significantly higher cancer rates (p=0.040) and a higher trend of IE (p=0.062). The median OS for the entire group was 1.5 years, and at 2 years it was 27%. Both the Nazha stratification scale and the MIPSS-R were good predictors of OS (p=0.0021 and p=0.0008, respectively) in our population. The frequency and type of the mutations that we found were similar to those described in the literature. Mutations in TET/IDH are a special group of interest with potential clinical implications. The molecular risk scales of Nazha and MIPSS-R were useful tools to predict OS.