Evaluation of infectious complications in patients with myelodysplastic syndromes: a prospective cohort study from the Canadian MDS registry

Infections are a significant cause of morbidity and mortality in myelodysplastic syndrome (MDS). Precise estimates of infection frequency and severity with modern therapies are uncertain. We conducted a retrospective analysis of a prospective cohort enrolled in a Canadian MDS registry and characterized the frequency and severity of infectious complications. Among 1,115 patients enrolled in the registry from 2006 to 2022, 349 (31%) experienced fever/infection, 207 (19%) were hospitalized due to fever/infection, and 95 (9%) died from fever/infection. Patients with severe neutropenia (absolute neutrophil count < 0.5 x 109/L) experienced more fever/infection (40% vs. 30%; p = 0.05), shorter time to fever/infection (7 vs. 25 months; p < 0.01) and more hospitalization for fever/infection (9 vs. 27 months; p < 0.01). Higher-risk MDS patients (Revised International Prognostic Scoring System > 3.5) had more fever/infection (36% vs. 29%; p = 0.05), infection-related hospitalizations (24% vs. 14%; p < 0.01), and a trend toward higher mortality due to fever/infection (11% vs. 7%; p = 0.06). Hypomethylating agent (HMA) treatment was associated with higher rates of fever/infection (40% vs. 26%; p < 0.01), as well as increased infection-related hospitalization (27% vs. 14%; p < 0.01) and death (14% vs. 6%; p < 0.01). Multivariate analysis showed that higher-risk disease and HMA treatment contributed to poorer infection-related outcomes including a shorter time from diagnosis to fever/infection (HR 1.9; p < 0.01 and HR 1.8; p < 0.01, respectively), hospitalization (HR 2.5; p < 0.01 and HR 1.9; p < 0.01, respectively), and death (HR 2.3; p = 0.01 and HR 3.3; p < 0.01, respectively). In a Canadian MDS population, infectious events were common with baseline neutropenia, higher-risk disease, and hypomethylating agents associated with increased infection risk.