Nathanael R. Fillmore
Publications / 2026
paper
EJHaem2026doi:10.1002/jha2.70352

Association of Frailty With Transfusions, Hospitalizations, and Survival in Patients With Myelodysplastic Syndrome Initiating Hypomethylating Agents.

Anahid Hamparsumian†, Jennifer La†, Mayuri Dharne, Gary Gilbert, Mary T. Brophy, Nhan V. Do, Dae Hyun Kim, Jane A. Driver, Nathanael R. Fillmore‡, Clark DuMontier‡

† Equal first authorship · ‡ Equal senior authorship

Summary

Patients with myelodysplastic syndrome who experience moderate-to-severe frailty face a 49% higher risk of death and increased rates of hospitalization and blood transfusions while receiving hypomethylating agents. These findings suggest that functional status is a critical prognostic indicator that should be integrated into clinical assessments to better predict outcomes and personalize care for this population.

Key result

Moderate-to-severely frail veterans with myelodysplastic syndrome initiating hypomethylating agents had a 49% higher hazard of death (aHR, 1.49; 95% CI, 1.34-1.67), along with increased rates of transfusions (aIRR, 1.61; 95% CI, 1.45-1.80) and hospitalizations (aIRR, 1.58; 95% CI, 1.51-1.64).

Abstract

INTRODUCTION: Prognostic scoring systems in MDS lack functional status measures. We sought to evaluate the influence of frailty on overall survival and care utilization in a national cohort. We conducted a retrospective study in the US Veterans Affairs Healthcare System of patients with MDS initiated on hypomethylating agents (HMAs) from 2004 to 2023. Frailty was measured using the Veterans Affairs-Frailty Index (VA-FI). METHODS: For primary analyses, we evaluated the association between severity of frailty and overall survival via Kaplan-Meier analysis, followed by Cox proportional hazard regression models. Multivariable Poisson regression was used to evaluate transfusion incidence and unplanned hospitalizations. We identified 2285 veterans with MDS who initiated HMA treatment. The median age was 73.2 years. In addition, 34.0%, 30.6%, and 35.4% of veterans were classified as non-frail, mildly frail, and moderate-to-severely frail, respectively. RESULTS: Moderate-to-severely frail veterans had a 49% higher hazard of death (aHR, 1.49; 95% CI, 1.34-1.67), as well as a higher incidence of transfusions (aIRR, 1.61; 95% CI, 1.45-1.80) and hospitalizations (aIRR, 1.58; 95% CI, 1.51-1.64). CONCLUSION: Increasing frailty was associated with higher rates of death, hospitalizations, and transfusions. Further research is needed to characterize how MDS-related contributors to frailty and non-oncologic aging-related factors mediate the increased risk of inferior outcomes in this population. TRIAL REGISTRATION: The authors have confirmed clinical trial registration is not needed for this submission.

Key figure

Key figure from Association of Frailty With Transfusions, Hospitalizations, and Survival in Patients With Myelodysplastic Syndrome Initiating Hypomethylating Agents.