Hairy cell leukemia 2022: Update on diagnosis, risk‐stratification, and treatment

Abstract

Disease Overview: Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders characterized by the identification of hairy cells, a specific genetic profile, a different clinical course, and the need for appropriate treatment. Diagnosis: Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation. Risk Stratification: Progression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood, and the immunoglobulin heavy chain variable region gene mutational status. VH4-34-positive HCL cases are associated with a poor prognosis. Treatment: Patients should be treated only if HCL is symptomatic. Chemotherapy with risk adapted therapy purine analogs (PNAs) are indicated in first-line HCL patients. The use of chemo-immunotherapy combining PNAs and rituximab (R) represents an increasingly used therapeutic approach. Management of relapsed/ refractory disease is based on the use of BRAF inhibitors (BRAFi) plus rituximab or MEK inhibitors (MEKi), recombinant immunoconjugates targeting CD22 or BrutonTyrosine Kinase inhibitors (BTKi). However, the optimal sequence of the different treatments remains to be determined. The Bcl2-inhibitors (Bcl-2i) can play a major role in the future. | INTRODUCTIONHairy cell leukemia (HCL) is recognized as an entity by the World Health Organization since 2008 1 and in the last 2017 revision of the WHO classification of lymphoid neoplasms. 2 HCL, four to five times more frequent in men than women, accounts for 2% of all leukemias with approximately 1.100 new HCL cases in the United States. 3 The few available population-based studies are limited. [4][5][6][7][8] When including HCL and HCL-like disorders, the overall age-adjusted to the 2000 US population incidence rate is 0.7 per 100 000 in men and 0.3/100 000 in women. When adjusting to the worldwide population, the incidence rate of HCL is 0.3 and 0.1/100 000, respectively, and remains relatively stable over time. 8 It is lower in non-Hispanic/black, Hispanic, or Asian/pacific Islander. Despite an improvement of overall (OS) and relative survival (RS), a significantly lower OS is observed among African American individuals compared with other ethnic groups. 6 The mortality rates for patients with HCL is similar to those of the general population 5 years after diagnosis. 9 HCL must be differentiated from other

Immunophenotypic Analysis of Hairy Cell Leukemia (HCL) and Hairy Cell Leukemia-like (HCL-like) Disorders

“…Patients with HCL and vHCL should be treated only if they are symptomatic [ 21 ]. Chemotherapy with purine analogs (PNAs) is indicated in the first line.…”

Hairy Cell Leukemia Patients Have a Normal Life Expectancy—A 35-Year Single-Center Experience and Comparison with the General Population

“…On the other hand, Lopez and co-workers [ 20 ] reported longer median treatment-free survival in 42 MRD-free HCL patients (not reached) compared to 40 MRD-positive HCL patients (97 months, range: 38–156 months; p = 0.059). With these conflicting results with regard to its clinical significance and consequence in mind, detection of MRD as identified by immunochemistry or immunophenotyping analysis of BM has not found entrance into clinical practice yet [ 21 ]. Of interest, however, 8-color flow cytometry monitoring of HCL cells in PB may allow identification of patients at high risk for clinical relapse.…”

Hairy cell leukemia: a specific 17-gene expression signature points to new targets for therapy

“…NIK could constitute a new therapeutic target for MCL treatment in cases of resistance to ibrutinib. Use of ibrutinib is an option in relapsed/refractory HCL patients (Troussard et al 2021 ). In a multicenter phase 2 study, ibrutinib was evaluated in 37 patients either with cHCL ( n = 28) or vHCL ( n = 9 patients).…”