This 2026 update reviews the diagnosis, risk-stratification, and treatment of hairy cell leukemia (HCL) and HCL-like disorders (HCL variant and splenic diffuse red pulp lymphoma), covering immunophenotyping, genetic markers, prognostic factors, and treatment sequencing.
First-line treatment with purine analogs (e.g., cladribine) remains standard; chemo-immunotherapy combining cladribine plus rituximab is increasingly used. Relapsed/refractory disease is managed with BRAF inhibitors + rituximab, MEK inhibitors, BTK inhibitors, and/or Bcl-2 inhibitors. Poor prognosis is associated with VH4-34–positive HCL, TP53 mutations, unmutated IGHV status, and HCL variant.
As a narrative review/update, it does not present new primary trial data or head-to-head comparisons between targeted agents. The optimal treatment sequence for relapsed/refractory disease remains undefined.
Treat HCL only when symptomatic; use cladribine ± rituximab in first-line therapy. For relapsed/refractory disease, consider BRAF inhibitor–based regimens, and flag VH4-34 positivity or TP53 mutations as high-risk features requiring closer follow-up.
Explore related topics
