Paper Details

ABSTRACT

Introduction: Hairy cell leukemia (HCL) is a rare, indolent B-cell lymphoproliferative disorder characterized by pancytopenia, splenomegaly, and a distinct immunophenotype. While most patients eventually require treatment due to symptomatic cytopenias, or organomegaly, a subset remains untreated for extended periods, either due to asymptomatic or indolent disease at diagnosis. Data in the untreated population is limited, and most published cohorts focus on patients that require therapy, and on treatment outcomes. Understanding the clinical, demographic, and molecular features of untreated HCL patients, may help inform the natural history of the disease and guide criteria for observation versus early intervention. Using data from the Hairy Cell Leukemia Patient Data Registry, an international multi-center registry, funded by Hairy Cell Leukemia Foundation (HCLF), we describe the clinical characteristics of patients with HCL who have remained untreated.

Methods: We performed a retrospective cohort descriptive study using the hairy cell leukemia data registry, an international multi-center registry of HCL patients, funded by the Hairy Cell Leukemia Foundation. The registry has collected information from 1970 until 2026. Untreated patients until this date included in the registry, were obtained. Demographic variables, comorbidities, diagnostic clinical and pathologic information was collected and described.

Results: A total of 822 patients met eligibility criteria and were included in the analysis, among these, 83 (10.1%) patients remain untreated. For this group the mean age at diagnosis was 62.14 ± 11.73 years. Male patients comprised the majority of the cohort (65.1%). White patients represented the largest racial group (83.1%), followed by unknown race (14.5%), Asian (1.2%) and African American (1.2%). Most of the patients were non-smokers at diagnosis (74.3%), 2.7% were active smokers, and the remaining were ex-smokers (23%). Immunophenotyping was made primarily by flow cytometry in 85.5% of patients, whereas immunohistochemistry was exclusively used in 8.4% of patients. The majority of patients had expression of CD11c (83%), CD103 (80.7%), CD20 (78.3%), CD19 (71.1%), and CD25 (62.7%). Less commonly patients also had expression of CD5 (7.2%), CD23 (4.8%), and CD27 (2.4%). BRAF status was assessed in 53% (44/83) of patients. Of these, 40% (18/44) were positive either by IHC and/or molecular testing, MAP2K1 mutation was tested in 1.2% of patients, and a TP53 mutation was tested and found in 7.2% of patients.

Conclusions: In this large international registry-based cohort, approximately 1 in 10 patients with HCL remained untreated. This population is predominantly white, male and diagnosed at a mean age in the early sixties. Immunophenotypic findings were largely consistent with classic HCL, with high rates of CD11c, CD103, CD20, CD19, and CD25 expression. Notably, BRAF status was assessed in only about half of untreated patients from this cohort, among whom 40% tested positive. This lower testing rate might reflect, both the registry’s long time span, as BRAF V600E mutation was not identified in HCL until 2011, in addition to a potentially reduced clinical motivation to pursue molecular testing in patients not undergoing treatment. Underreporting of testing is also a possibility. TP53 mutations were identified in a minority of patients. These findings suggest that a clinically meaningful number of HCL patients can be safely observed without treatment. Additional studies are needed to further characterize the factors associated with prolonged treatment-free survival. With recent MRD implementation, it would also be meaningful to assess MRD trends in this population.