Infection Linked With Nearly a Quarter of Deaths in Lower-Risk MDS

Infection was the main cause of death among a cohort of patients with lower-risk myelodysplastic syndromes (LR-MDS), accounting for approximately 1 in 4 deaths within a year of diagnosis, according to a study published in Haematologica.¹ The authors identified several risk factors for infection and infection-related death and highlighted the importance of monitoring patients with LR-MDS closely for symptoms of infection.

While research has focused on risk factors for infection and infection-related deaths among patients with high-risk MDS (HR-MDS), risk factors for infection have not been thoroughly explored in those with LR-MDS, the study authors explained.

Patients with LR-MDS, particularly those with the highest rates of infection-related deaths, would benefit from close monitoring for infections. | Image credit: Saiful52 - stock.adobe.com

“There are reasons to assume that the risk factors for infections in patients with LR-MDS might be different from those of patients with HR-MDS due to differences in disease pathophysiology, course, and treatment,” they wrote. “The risk of infections in patients with HR-MDS is increased mainly due to a higher risk of transformation to AML [acute myeloid leukemia] and more pronounced bone marrow suppression compared to patients with LR-MDS.” Treatment is also more intensive for HR-MDS, they added, and chemotherapy-induced neutropenia, treatment with hypomethylating agents, and worsening of pre-existing cytopenias may independently increase the risk of infections.

The study aimed to determine the prevalence and risk factors for infections and infection-related deaths within 1 year of diagnosis of LR-MDS. Data from the prospective European LeukemiaNet MDS (EUMDS) registry, which includes newly diagnosed patients with all subtypes of MDS,² were used in the analysis.

A total of 2552 patients from the EUMDS registry were included in the study, with a mean age at diagnosis of 74 years (range, 18-97 years).¹ There were 1074 patients (42.1%) categorized as Revised International Prognostic Scoring System (IPSS-R) low risk and 1024 (40.2%) categorized as intermediate-1 risk. A total of 452 patients (17.7%) could not be properly scored due to a lack of cytogenetic testing, but these patients were presumed to fall into the LR-MDS cohort based on the number of cytopenias and bone marrow blasts reported.

The prevalence of infections was 7.6% within the first year of follow-up, and 43.2% of infections occurred within 100 days of MDS diagnosis. Additionally, one-third of infectious episodes led to death.

Of the 297 deaths that occurred within a year of follow-up, 24.6% were due to infections. This was the most common cause of death in the study population. More patients in the group who experienced infections died within a year of follow-up (49.2%) compared with the patients who did not experience an infectious episode (8.6%). AML was the most common cause of death in patients who did not experience infectious episodes (1.1% vs 19.3%, respectively).

Several factors, including an intermediate or higher IPSS-R risk group, severe anemia, severe thrombocytopenia, poorer cytogenetics, and having received a red blood cell transfusion at diagnosis, were linked with increased risks of infections and infection-related death within 1 year of follow-up.

Study limitations included lacking data on the site, type, and severity of infection in the study population, as well as a lack of criteria around what types of infections warrant reporting. Therefore, there may have been an underestimation of infectious episode prevalence and overestimation of mortality, as infections requiring hospitalization or leading to death were likely reported more comprehensively compared with infections that were less severe, the authors noted. The date of infections was also not reported, making it impossible to evaluate data longitudinally or extend follow-up duration.

Despite these limitations, the authors concluded that patients with LR-MDS, particularly those with the highest rates of infection-related deaths—older patients and patients with severe anemia, thrombocytopenia, poor cytogenetics, and red blood cell transfusions—would benefit from close monitoring for infections. If these patients experience infectious symptoms, providers should be diligent in monitoring and addressing these symptoms.

“Future research should focus on the type of infections and causative pathogens in patients with LR-MDS, as this is crucial data for preventive strategies in patients at highest risk for infections, such as prophylactic antibiotics,” the authors wrote. “Certain criteria for the definition of infections could be used to generate more generalizable results and to give a better estimate of the incidence or prevalence of infections. Furthermore, evaluation of the evolution of dynamic risk factors in relation to developing infections, such as cytopenias, iron-overload and transfusion dependency, is of importance to better estimate the risk for infections and infection-related mortality over time. This could improve preventive strategies, monitoring, and treatment for patients at risk for infections.”

References

1. Houtman B, Taylor A, Van Marrewijk C, et al. Infections in lower-risk myelodysplastic syndromes - prevalence and risk factors: a report from the European MDS Registry. Haematologica. Published online April 10, 2025. doi:10.3324/haematol.2024.286880
2. European Myelodysplastic Syndromes (MDS) Registry. EUMDS Registry. Accessed April 30, 2025. https://eumds.org/