INTRODUCTION Chronic lymphocytic leukemia (CLL) predominantly affects older adults and is frequently managed expectantly, yet treatment decisions still lean heavily on chronological age. Frailty may capture physiologic vulnerability that age alone misses, but population-level data on its burden and prognostic value in patients hospitalized with CLL remain sparse. We examined whether frailty is associated with in-hospital outcomes in patients with CLL across the United States and whether that association persists independent of age. MATERIALS AND METHODS We identified hospitalizations of adults with CLL from the 2017 to 2022 US Nationwide Inpatient Sample (NIS). The Hospital Frailty Risk Score stratified patients into low, intermediate, and high frailty. Endpoints were in-hospital mortality, unfavorable discharge, prolonged length of stay, and total hospital cost. Multivariable regression adjusted for age, sex, race, insurance status, income quartile, Elixhauser comorbidity sum, hospital characteristics, and calendar year, using NIS weights. Analyses were restricted to patients not having achieved remission. RESULTS Among 97,325 patients hospitalized with CLL, more than half were in intermediate or high frailty groups, and mean age rose across frailty tiers (72.8, 76.6, and 80.5 years). In multivariable analyses, higher frailty was associated with higher risk across all endpoints. Compared to low frailty, high frailty was associated with a higher risk of in-hospital mortality (aOR 4.74, 95% CI 4.19-5.37), unfavorable discharge (aOR 7.33, 95% CI 6.83-7.87), and prolonged length of stay (aOR 4.83, 95% CI 4.50-5.19). Mean hospital costs rose from $59,674 in the low frailty group to $101,959 in the high frailty group. The association between frailty and mortality held across all adult age subgroups, with the strongest relative effect observed in patients aged 40-59 years. Results in the youngest subgroup warrant cautious interpretation given small sample size. DISCUSSION Frailty is common among patients hospitalized with CLL and independently predicts in-hospital mortality, unfavorable discharge, prolonged length of stay, and higher costs, with an effect that persists across age groups. These findings support incorporating frailty assessment, rather than age alone, into risk stratification for older adults hospitalized with CLL and motivate prospective evaluation of whether frailty-guided care improves outcomes.
