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Hairy cell leukemia (LHCL) accounts for 2% of all leukemias. Its diagnosis is based on the presence in the blood and/or the marrow of hairy cells: abnormal B lymphoid cells with a hairy cytoplasm expressing CD103, CD123, CD11c, and CD25. The BRAF V600E mutation of the proto-oncogenic B-Raf gene (BRAF), a molecular marker of the disease, is present in more than 80% of cases. HCL should be distinguished from other chronic B lymphoproliferative syndromes and in particular from other hairy cell proliferations, including the variant form of hairy cell leukemia (HCL-V). Progress has recently been made in the management of HCL patients. Purine nucleoside analogs (PNAs) in monotherapy—either deoxycoformycin or 2-chloro-2’-deoxyadenosine— remain the first-line treatment option. PNAs alongside anti-CD20 monoclonal antibodies (rituximab, obinutuzumab) are now being introduced as the first-line treatment in young and fit patients. Immunochemotherapy allows for prolonged complete remissions. In patients with relapsed/refractory HCL, new therapeutic options—immunotoxins, BRAF inhibitors (BRAFi), or Bruton Tyrosine Kinase inhibitors (BTKi)—require discussion. In patients with HCL-V who do not have the BRAF V600E mutation but mutations in mitogen-activated protein kinase kinase 1 (MAP2K1) in about a third of cases, immunochemotherapy has become the standard first-line treatment. In all cases, prolonged hematological monitoring is necessary, because of the increased risk of secondary cancer and in particular that of malignant hematological disorders. Complex cases are to be discussed during national multidisciplinary consultation meetings, which will be organized very soon.