P086 | DIAGNOSIS AND MANAGEMENT OF CHRONIC MYELOMONOCYTIC LEUKEMIA: THE EXPERIENCE OF THE HEMATOLOGY CLINIC OF ANCONA

Background: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem and progenitor cell disorder characterized by persistent peripheral blood monocytosis and bone marrow dysplasia. CMML carries an inherent risk of progression to acute leukemia, with the probability of transformation assessed through various prognostic scoring systems like CPSS and CPSS-mol. Aims: This study retrospectively evaluates clinical features, prognostic factors, and therapeutic outcomes in patients diagnosed with CMML at the Hematology Clinic of Ancona. Methods: We analyzed 41 CMML patients, with a median age of 77 years. Risk stratification was performed using FAB, WHO 2022, cytogenetic score, CPSS, and CPSS-mol classifications. Cytogenetic and molecular profiles were assessed via standard karyotyping and NGS. Results: Most patients exhibited a myelodysplastic phenotype (73%) and WHO CMML-1 subtype (78%). Cytogenetic abnormalities were present in 21.7%, primarily trisomy 8 and monosomy 7. Molecular analysis revealed a high mutational burden, with almost all patients harboring at least one mutation and a median of three mutations per patient. The most frequently mutated genes were TET2 (57.6%), SF3B1 (30.7%), SRSF2 (23%), RUNX1 (23%), and ASXL1 (19.2%). Median overall survival (OS) was 87.2 months, significantly shorter in patients over 70 years, transfusion-dependent, bone marrow blasts > 5%, FAB myeloproliferative subtype, high-risk cytogenetics, or high-risk CPSS-mol scores. SF3B1 mutations correlated with favorable prognosis, while ASXL1 mutations were linked to poor outcomes. TET2 did not have a prognostic role. First-line therapeutic approaches varied: 31,7% watch and wait strategy, 21,9 % received ESAs, 2,4% eltrombopag (off-label), 29,3 % were treated with hydroxyurea and 12,5% with hypomethylating agents. Although two patients were eligible for allogeneic stem cell transplantation, only one proceeded to transplantation as a second-line therapy. OS was longer in patients managed supportively compared to those receiving cytoreductive or hypomethylating therapies. Progression to acute myeloid leukemia occurred in 20.7% of cases associated with NRAS mutations, high-risk cytogenetics, and adverse CPSS-mol scores. Conclusions: Our study underscores the clinical and molecular heterogeneity of CMML and the prognostic relevance of cytogenetic and mutational profiles. Personalized risk stratification and treatment remain critical in improving CMML patient outcomes.