Background: Hairy cell leukemia (HCL) is a rare indolent B-cell malignancy classically characterized by the presence of the BRAF V600E mutation, which has important diagnostic and therapeutic implications. BRAF V600E–negative HCL is uncommon, often poses diagnostic challenges, and is generally considered less responsive to standard purine nucleoside analog therapy.
Case Presentation: We report the case of a 42-year-old man who was incidentally found to have pancytopenia during routine blood donation. Initial evaluations suggested chronic lymphocytic leukemia, and the patient was treated with rituximab, corticosteroids, and subsequently ibrutinib, without clinical or hematologic improvement. Progressive cytopenia and splenomegaly prompted reevaluation. Repeat bone marrow examination and immunophenotyping were consistent with hairy cell leukemia. Molecular analysis for the BRAF V600E mutation was negative. Despite the reported lower sensitivity of BRAF-negative HCL to purine analogs, the patient was treated with cladribine in a 21-day regimen along with appropriate antimicrobial prophylaxis. Following therapy, the patient demonstrated gradual and sustained recovery of blood counts, achieving complete hematologic remission. on 5th month follow-up; the patient’s blood counts were normal and sustained remission was achieved.
Conclusion: This case highlights the importance of considering hairy cell leukemia in patients with atypical or treatment-refractory chronic lymphoproliferative disorders. It also demonstrates that selected cases of BRAF V600E–negative HCL may respond favorably to cladribine. Further studies are needed to better define the optimal management strategies for this rare HCL subset.