INFECTIOUS COMPLICATIONS IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES AND CORRELATED MYELOID NEOPLASM TREATED WITH AZACITIDINE: AN UNICENTRIC COHORT

Abstract

Introduction: Although the survival benefit of azacitidine in patients with high-risk myelodysplastic syndrome (MDS), oligoblastic acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) has been proven, few studies on infections have been published. This study aims to analyze infectious complications in patients with MDS, oligoblastic AML, and CMML treated with azacitidine. Objectives: Evaluate infectious complications in MDS and correlated myeloid neoplasms (MN) patients treated with azacitidine. Material and methods: Retrospective analysis of infectious complications in patients over 18 with MDS and related MN (de novo or therapy-related) treated with azacitidine at a single clinic from 2009 to 2021. Data were collected from REDCap medical records. Survival was analyzed by Kaplan-Meier, and univariate and multivariate analyses were conducted using Cox regression. Results: A total 72 patients were included: 57 MDS (79%), 7 AML (9.7%), and 8 CMML (11%); 63% males, median age 62 years-old, 48 high/very high risk IPSS-R. Sixty nine patients were on antibiotics, mainly levofloxacin. Twenty-three (32%) patients had severe infection (SI), 15 (21%) mild/moderate infection (MI), and 34 (47%) no infection (NI). Univariate analysis showed higher proportions of SI (74%) and MI (80%) in high/very high-risk IPSS-R patients compared to NI (56%). Severe neutropenia and thrombocytopenia, and higher ferritin levels were associated with SI risk in the univariate analysis and thrombocytopenia marginally at multivariate analysis (p = 0.069). There were 72 infectious episodes over 739 cycles, 96% with antibacterial prophylaxis. Infection incidence was highest in the first four cycles, peaking at 26% in the second cycle and decreasing to 2.8% by the eighth cycle. Eight percent of patients required dose reductions, and 29% had cycle delays due to infections. Of the infections, 52% were severe and 48% mild/moderate (CTCAE 5.0); 8.4% were microbiologically defined, 47.2% clinically defined and 44.4% fever of unknown origin. The cumulative infection incidence was 47% at 6 months and 68% at 1 year. Event-free survival was 1.26 years, median overall survival (OS) of 38.43, 16.75 and 11.14 months in NI, MI and SI patients, respectively. Infections were the cause of death in 9.8% of patients and in 39% of those with severe infections (p < 0.001). Discussion: Infectious complications were associated with decreased OS of patients treated with azacitidine. Infection rates in the first three cycles were consistent with existing literature. Despite bacterial prophylaxis, no bacterial resistance was found. Thrombocytopenia was the main variable associated with higher infection risk, as previously described in previous studies. Conclusion: In this unicentric outpatient study, patients with MDS and thrombocytopenia are at greater risk of developing infection, especially in the first cycles and should be monitored cautiously. Although infection is associated with reduced survival, death generally occurs due to other causes, such as disease progression.