Paper Details

ABSTRACT

Introduction: 

Hairy cell leukemia (HCL) is a rare b-cell malignancy with a generally favorable prognosis with some studies indicating patients can expect a normal lifespan compared to the general population. Despite this, long-term mortality patterns and disparities across demographic subgroups have not been thoroughly explored. Prior studies have suggested improved survival outcomes with modern therapies such as purine analogues, yet questions persist regarding whether mortality differs by sex, race, or relative to non-malignant comparator populations.  Additionally, the impact age at diagnosis has on long-term survival could use further clarification. This study aimed to evaluate all-cause mortality in a large cohort of patients with HCL compared to a matched non-malignant control group, and to examine differences in mortality within the HCL population by sex, race, and age at diagnosis. 

Methods: 

The TriNetX Research Network (TNX) contains the aggregated and de-identified healthcare records of over 144 million patients across 110 healthcare organizations. We queried TNX for patients with a diagnosis of HCL (ICD-10: C91.4). A control cohort of patients diagnosed with vitamin B12 deficiencyanemia (ICD-10: D51) were identified; B12 deficiency serves as a non-malignant, healthcare-engaged comparator with low intrinsic mortality with similar demographic and comorbidity profiles. Nearest-neighbor propensity score matching was performed on demographics (age, sex, race, ethnicity), comorbidities (hyperlipidemia, hypertension, ischemic heart disease, obesity, diabetes, chronic kidney disease, chronic respiratory disease, liver disease, prior malignancy), and healthcare utilization. The primary outcome of interest was all-cause mortality. Subgroup analyses were performed for HCL patients split by sex (male vs. female), race (White vs. Black), and age (>62 vs. <=62 years). All analyses were performed on December 20, 2025. 

Results: 
We identified 7,402 patients with HCL within TNX. After propensity score matching, 6,860 patients with HCL (mean age 62.0 SD 15.4 years) were successfully matched to 6,860 individuals with vitamin B12 deficiency (mean age 62.8 SD15.0 years). 76.1% (5223) of the HCL cohort and 77.2% (5293) of the vitamin B12 deficient cohort were male. Over a 20-year follow-up period, there was no significant difference in all-cause mortality between the two groups (HR 0.99; 95% CI 0.91-1.08; p=0.82), indicating comparable long-term survival. Within the HCL cohort, mortality did not significantly differ by sex, with men and women demonstrating similar outcomes (HR 1.05; 95% CI 0.87-1.27; p=0.58). Similarly, no statistically significant difference in mortality was observed between White and Black patients (HR 1.30; 95% CI 0.85-1.97; p=0.23. In contrast, age at diagnosis emerged as a significant determinant of mortality risk. Patients diagnosed after age 62 had a markedly higher hazard of all-cause mortality compared to those diagnosed at or before age 62 (HR 2.43; 95% CI 2.03-2.91; p<0.0001). 

Conclusion: 

In this large, propensity score-matched analysis, patients with HCL demonstrated long-term all-cause mortality comparable to a matched cohort with vitamin B12 deficiency, supporting the generally favorable prognosis of HCL. Within the HCL population, survival outcomes were consistent across sex and racial groups, suggesting limited disparities along these dimensions, although further studies with larger minority representation are warranted. Notably, age at diagnosis was strongly associated with mortality, with older patients experiencing significantly worse outcomes. These findings highlight the importance of age as a key prognostic factor in HCL and underscore the need for tailored management strategies in older individuals.