MDS-308: Mutational Profile of Patients Diagnosed with Myelodysplastic Syndromes, First Experiences in a Center of Argentina

Abstract

Context: Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are heterogeneous myeloid malignant clonal disorders. Different mutations can be associated with higher risks of these diseases, specific characteristics, and responses to certain treatments. Molecular findings obtained through next-generation sequencing (NGS) have gained importance in myeloid neoplasms, but local access is limited. We recently incorporated NGS technology in our center that will seek to identify mutations. Objective: To describe the mutational landscape of patients diagnosed with MDS and CMML locally. Design: We designed a prospective observational cohort study from July 2019 to July 2020 in adult patients diagnosed with MDS and CMML who underwent bone marrow biopsy with NGS at a private university reference hospital, Hospital Italiano, in Buenos Aires. Results: 24 adult patients with MDS and CMML diagnosis were included, 18 MDS and 6 CMML. The median age was 74 years (IQR: 60–78.25), 54% male. All patients were classified with IPSS-R. NGS was performed in all patients; 86.9% had at least one mutation. Among the most frequent genes were TET2, SRSF2, DNMT3A, and RUNX1. Five of six patients with CMML had a normal karyotype; all obtained at least three mutations, and SRF2 mutation was the most frequent. The most common mutational pathways involved in patients with adverse cytogenetics were DNA repair and transcription pathways (p = 0.019). The number of mutations in patients with high-risk IPSS-R was 3.5 vs 2 mutations in low-risk patients, which was not statistically significant. The mean Hb value in patients with 2 mutations or fewer was 10.3 mg/dl vs 9 mg/dl in patients with > 3 mutations (p = 0.069). Treatment was required in 50% of patients with 1–2 mutations and in 86% of patients with 3 mutations or more (p = 0.016). Conclusions: As described in the literature, most of our patients had mutations, the most frequent being epigenetic regulators and signal translation genes. The number of mutations was statistically correlated with the degree of anemia and with treatment indication. Recognizing mutations is crucial for clinical decisions, diagnosis, prognosis, and treatment. Although we have evaluated few patients, our data are comparable to those published and encourage us to continue working to improve the care of our patients.