Dear Colleague,

Hairy cell leukemia is a very rare and well-defined entity that is characterized by atypical lymphoid cells with hairy projections in the peripheral blood, spleen, and/or liver. HCL represents 0.7% of all malignant hematological disorders and 3.0% of all leukemia. Based on the estimated 2019 leukemia incidence of 61,780 in the United States, approximately 1240 new HCL cases are expected per year. In 2013, the estimated number of new cases was 1417 cases in the European Union, and it was 304 new cases in France in 2018.

The few available population-based studies are limited. Issues related to environmental and exposure risk factors in HCL are unclear. The protective role of cigarette smoking was demonstrated, and an increased risk in people who live or work on a farm was established. However, the etiology of HCL remains unknown. The risk of secondary cancer is high, especially that of another hematologic disorder. Efforts are needed to undertake more extensive epidemiological studies to determine the role of occupational and environmental risk factors in the development of HCL and HCL-like disorders. HCL-like disorders are well-defined entities, although overlaps exist between HCL, variant forms of HCL (HCL-v), splenic diffuse red pulp lymphoma, and splenic marginal zone lymphoma.

HCL is a fascinating disease, which was initially described in 1958. There is an urgent need today to improve HCL diagnosis and management, particularly since this is a period of an unprecedented health crisis. HCL is four to five times more frequent in men than in women. Unusual clinical manifestations are occasionally reported and can make the diagnosis of HCL in daily practice difficult and complex. This is the case for HCL patients with bulky abdominal lymph nodes, tumor masses, bone lesions or leukemia cutis. Accurate diagnosis relies on the recognition of hairy cells by morphology and flow cytometry (FCM) in the blood and bone marrow. Unlike other HCL-like disorders, HCL scores 3 or 4 on the hairy cell panel (CD11c, CD25, CD103, CD123), because most HCL cells predominantly express these markers. The V600E mutation of the B-raf proto-oncogene (BRAF gene) (7q34) in exon 15 is detected in approximately 80% of cases: the mutation is crucial and is considered a driver mutation but likely not sufficient to trigger disease. The development of high-throughput sequencing techniques makes it possible to better define the mutational landscape of HCL and HCL-like disorders. Finally, we also have to better identify HCL patients with a high risk of relapse (absence of somatic mutations in IGHV genes, VH4-34 family usage, TP53 mutation) and establish national and international networks to facilitate access to molecular platforms and to set up quality certificates to guarantee safe and high-quality care specific to unmutated IGHV4-34 HCL and HCL-like disorders.

Thanks to significant clinical advances in clinical management, varied treatment options are available, e.g., watch-and-wait strategy in asymptomatic patients and chemotherapy or chemoimmunotherapy in first or second line of treatment. However, therapeutic modalities which are less toxic and better tolerated are needed. For patients in relapsed or refractory disease, several options exist with new drugs and targeted therapy, but the question remains of which of them is truly the best choice. The optimal treatment for HCL-v patients remains to be determined.

Prof. Dr. Xavier Troussard
Guest Editor

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• hairy cell leukemia
• HCL-like disorders
• splenic diffuse red pulp lymphoma
• HCL variant