Hairy Cell Leukemia

Hairy cell leukaemia (HCL) is an indolent mature B cell neoplasm with BRAF V600E mutation, pancytopenia and splenomegaly.

• Rare (2% of leukaemias), middle aged men (5:1), median age 55.
• Hairy cells express CD11c, CD25, CD103, CD123, annexin A1, TRAP.
• Variant HCL (HCL-V) lacks CD25 and BRAF V600E and is more aggressive; IGHV4-34 mutated type.
• Complications: infections (monocytopenia, atypical mycobacteria), vasculitis, splenic rupture, bone lesions.

• Fatigue, weakness, recurrent infection, bruising, abdominal fullness.
• Splenomegaly (80 to 90%), no lymphadenopathy, pancytopenia, monocytopenia.
• Associated vasculitis (polyarteritis nodosa), autoimmune phenomena.

• Blood film: hairy cells (cytoplasmic projections); pancytopenia; flow cytometry (CD19, CD20 bright, CD11c, CD25, CD103, CD123).
• Bone marrow: "dry tap", reticulin fibrosis, diffuse infiltrate with fried egg appearance; BRAF V600E by PCR or immunohistochemistry.
• Imaging for splenic size; hepatitis B, HIV screening.
• Exclude splenic marginal zone lymphoma, HCL-V, prolymphocytic leukaemia, myelofibrosis.

• Treat if symptomatic cytopenias (haemoglobin under 10 g/dL, platelets under 100 x 10^9/L, neutrophils under 1 x 10^9/L), recurrent infection, symptomatic splenomegaly.
• First line purine analogue: cladribine 0.09 mg/kg/day by continuous infusion for 7 days (or 0.14 mg/kg over 2 hours daily for 5 days), complete response in 85 to 95%; or pentostatin 4 mg/m2 every 2 weeks for 3 to 6 months.
• Add rituximab 375 mg/m2 weekly for 8 doses (concurrent or consolidation) for minimal residual disease eradication.
• Relapse: repeat purine analogue plus rituximab; BRAF inhibitor vemurafenib 240 to 960 mg twice daily (or dabrafenib with trametinib); moxetumomab pasudotox; ibrutinib.
• HCL-V: purine analogue with rituximab, alemtuzumab, splenectomy.
• Supportive: neutropenia (G-CSF), transfusions, infection prophylaxis (aciclovir, avoid live vaccines), fever management.
• Splenectomy for splenic rupture risk or refractory disease.
• Monitor blood counts and minimal residual disease; relapse frequent after 10 years.