Precision-guided therapy in dialysis-dependent classic hairy cell leukemia: a case report.

BACKGROUND: Classic hairy cell leukemia (HCL) is a rare, indolent B-cell lymphoproliferative disorder characterized by bone marrow fibrosis causing pancytopenia, splenomegaly, and a near-universal BRAF V600E mutation. Purine nucleoside analogs (PNAs) are the standard first-line therapy but are contraindicated in patients with significantly advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD) due to renal excretion and risk of prolonged myelosuppression. Data on the use of targeted therapies, such as BRAF inhibitors, in dialysis-dependent HCL patients are lacking. CASE: We present a novel case of a 43-year-old man on chronic hemodialysis secondary to suspected autosomal dominant polycystic kidney disease diagnosed with classic BRAF V600E-mutated HCL, treated with low-dose vemurafenib in combination with anti-CD20 therapy. The patient achieved hematologic remission without significant renal or infectious complications. Notably, this case is further distinguished by the development of reactive macrocytic polycythemia with normal erythropoietin levels and no alternative identifiable cause, highlighting an unusual hematologic manifestation in the setting of treated HCL and end-stage renal disease. DISCUSSION: This report highlights the feasibility and efficacy of BRAF-targeted therapy combined with an anti-CD20 antibody in a young dialysis-dependent HCL patient, expanding therapeutic options for this high-risk population. Further prospective studies and case series are needed to guide management in this unique clinical context.