A 60-year-old man presents with fatigue, recurrent infections, and massive splenomegaly (20 cm below costal margin). CBC shows pancytopenia with WBC 2,800/μL. Peripheral smear shows lymphocytes with circumferential cytoplasmic hairy projections. Which targeted therapy is most appropriate for initial treatment?
- A Ibrutinib, a Bruton tyrosine kinase inhibitor
- B Rituximab monotherapy, an anti-CD20 monoclonal antibody
- C Cladribine (2-chlorodeoxyadenosine), a purine analog ✓
- D All-trans retinoic acid (ATRA) combined with arsenic trioxide
Correct answer: C. Cladribine (2-chlorodeoxyadenosine), a purine analog
Explanation
Hairy cell leukemia is characterized by pancytopenia, splenomegaly, and cells with hairy projections expressing CD20, CD25, CD11c, CD103, and BRAF V617E mutation. Cladribine or pentostatin (purine analogs) induce durable complete remissions in over 80% of patients and are first-line therapy. Ibrutinib is used in CLL and Waldenström macroglobulinemia. ATRA with arsenic trioxide is for APL.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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