Long-term mortality trends in hairy cell leukemia: A comprehensive U.S. population analysis (1999-2023)

Hairy cell leukemia (HCL) is a rare indolent B-cell neoplasm with excellent survival outcomes following purine analog therapy. However, long-term national mortality trends remain underreported. This study aims to evaluate long-term patterns of HCL-related mortality and temporal changes in the United States. Methods:We analyzed CDC WONDER mortality records from 1999 to 2023 for individuals with HCL (ICD-10: C91.4). Age-adjusted mortality rates (AAMR) per 100,000 were calculated and stratified by age, sex, race, Hispanic origin, and place of death. Joinpoint regression (NCI Joinpoint v5.4.0, weighted BIC) identified annual percent changes (APC) and inflection points with 95% confidence intervals (CI). Results:A total of 4,496 HCL-related deaths occurred from 1999 to 2023. The overall AAMR declined from 0.056 in 1999 to 0.040 in 2018 (APC: -2.21; 95% CI: -6.37 to -1.29), followed by a nonsignificant increase to 0.043 in 2023 (APC: 5.07; 95% CI: -0.69 to 21.32). Among males, the AAMR decreased from 0.10 in 1999 to 0.07 in 2015 (APC: -2.22; 95% CI: -2.99 to -1.44), then significantly increased to 0.096 in 2023 (APC: 2.23; 95% CI: 0.69 to 3.80). Females demonstrated a continuous decline from 0.02 to 0.012 (APC: -2.35; 95% CI: -3.51 to -1.18). Mortality was concentrated in adults ≥65 years, with the highest rates in those ≥75 years (0.41-1.24 per 100,000). White individuals had the highest AAMR (0.061), followed by Black (0.020) and Asian or Pacific Islander (0.008). Non-Hispanic individuals accounted for 96% of deaths. Most deaths occurred in inpatient facilities (44%) or at home (26%). Conclusion: HCL-related mortality declined for nearly two decades but has begun to plateau, with a recent increase observed among males. Persistent declines among females contrast with increasing mortality in males, suggesting a widening difference in outcomes between the two groups. Mortality continues to be concentrated in older adults, reflecting the influence of age, comorbid illness, and treatment-related immunosuppression. Continued surveillance is needed to understand the factors driving these changes, including relapse patterns, treatment selection, and the challenges faced by an aging survivor population, to sustain progress and reduce emerging disparities.