Hairy Cell Leukemia
Summary of Key Points
• Hairy cell leukemia (HCL) is an uncommon clonal B-cell lymphoproliferative disorder.
• BRAF V600E mutation is present in nearly all cases of HCL but absent in other B-cell lymphoproliferative disorders and represents a disease-defining genetic event in HCL.
• Physical findings generally are confined to splenomegaly.
• The purine analogs are the therapeutic agents of choice.
• Most patients who receive treatment with cladribine or pentostatin have prolonged survival.
• BL22 or HA22, an immunoconjugate of an anti-CD22 antibody linked to a truncated Pseudomonas exotoxin A, is a novel agent that has been very effective in the management of relapsed and refractory HCL.
• BRAF inhibitors represent the first molecularly targeted therapy in HCL and will soon be explored in clinical studies.
1. A 65-year-old woman comes to your clinic with fatigue and an abnormal peripheral blood cell count noted during a routine physical examination. Laboratory evaluation is notable for a white blood cell count of 3,500/µL with 30% neutrophils and 68% lymphocytes, hemoglobin value of 11.0 g/dL, and platelet count of 76,000/µL. Her physical examination revealed marked splenomegaly. Peripheral blood smear showed a few cells, one to two times the size of a small lymphocyte, with hairlike projections. You suspect hairy cell leukemia (HCL) and sent peripheral blood for immunophenotypic analysis by flow cytometry. Which of the following staining patterns most likely support the diagnosis of HCL?
2. Which of the following mutations is found in nearly all patients with hairy cell leukemia but not in patients with other chronic B-cell lymphoproliferative disorders?
3. Which of the following agents has been studied in clinical trials for patients with relapsed HCL after treatment with purine analogs?
1. Answer: D. Hairy cells exhibit a mature B-cell phenotype and strongly express pan–B-cell antigens, including CD19, CD20, CD22, and CD79b. They usually stain negative for CD5, CD10, and CD23 and strongly express CD11c, CD25, and FMC7. CD103, an antigen expressed on mucosal T cells and some activated T cells, is expressed in a majority of cases of HCL.
2. Answer: B. A recent whole-exome sequencing study of HCL cells in parallel with normal cells has identified the presence of the BRAF V600E mutation in all of 48 tested cases of HCL. This initial finding has been extended and corroborated in larger cohorts of patients. The presence of the BRAF V600E mutation is now reported in more than 400 cases of HCL but not in more than 700 cases of other B-cell lymphoproliferative disorders.
3. Answer: D. The anti-CD20 monoclonal antibody rituximab and recombinant immunotoxins containing anti-CD22 monoclonal antibody and Pseudomonas exotoxins (BL22 and HA22) have been tested in patients with HCL refractory to purine analogs. The striking activity of the specific BRAF inhibitor vemurafenib has been reported only in one patient who was refractory to three lines of purine analog–based treatment. However, based on these preliminary clinical data and the exclusive presence of the BRAF V600E mutations in HCL, a multicenter clinical trial with the BRAF inhibitor in relapsed and refractory HCL is scheduled to open soon in the United States.
