New insights in the management of patients with hairy cell leukemia

Although hairy cell leukemia (HCL) was identified in 1958 by Bouroncle and colleagues, HCL remains in 2015 a mysterious disease. Accurate diagnosis of HCL relies on the recognition of hairy cells by morphology and flow cytometry in blood and/or bone marrow. However, there are cases difficult to diagnose, particularly in variants of HCL. Furthermore, some diseases such as splenic diffuse red pulp small B-cell lymphoma are very close to HCL and may be misdiagnosed. Major advances in the management of patients who have HCL have been made following the use of purine nucleoside analogs. However, new treatment options can be available in relapsed/refractory HCL: monoclonal antibody therapy, BRAF inhibitors, or immunotoxins.

The presence of the BRAFV600E mutation was recently identified in most cases of HCL and its absence in variants of HCL and in other B-cell chronic lymphoproliferative disorders. The precise cellular origin of HCL remains elusive but BRAF mutations were detected in hematopoietic stem cells of patients with HCL. Assessment for minimal residual disease is important in clinical trials. Minimal residual disease detection can clearly predict inferior long-term outcomes or early relapses in patients with HCL. Recent reports have shown that inhibition of BRAF kinase by drugs such as vemurafenib is effective in relapsed/refractory HCL. Immunotoxins offer new opportunities even in patients without BRAF mutations.

All these findings have major implications for diagnosis, monitoring, and treatment of HCL and variant forms of HCL.