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Expert Review of Hematology Mar 2019Hairy cell leukemia (HCL) is a rare, chronic B-cell lymphoproliferative disorder characterized by distinctive morphologic features and an indolent clinical course. The... (Review)
Review
Hairy cell leukemia (HCL) is a rare, chronic B-cell lymphoproliferative disorder characterized by distinctive morphologic features and an indolent clinical course. The discovery of a recurrent activating mutation in BRAF (BRAF V600E) as a disease-defining genetic event in HCL has substantial diagnostic and therapeutic implications. Areas covered: Herein the authors review the role of BRAF V600E and RAF-MEK-ERK signaling in the pathogenesis of HCL, anecdotal clinical reports of BRAF inhibitor monotherapy in management of relapsed or refractory HCL, larger phase 2 trials investigating efficacy of BRAF inhibitor therapy for HCL, adverse effects commonly associated with BRAF inhibitor therapy, including cutaneous toxicity, and mechanisms of therapeutic resistance. Expert opinion: Ongoing and planned studies will help to optimize the use of BRAF inhibitor therapy for HCL by determining the efficacy of BRAF inhibition in combination with other antigen targeted or molecularly targeted therapies, and more broadly, to determine how hematologists can best utilize and sequence emerging diagnostic and therapeutic modalities in the care of patients with newly diagnosed and relapsed or refractory HCL.
Topics: Animals; Antineoplastic Agents; Humans; Leukemia, Hairy Cell; MAP Kinase Signaling System; Point Mutation; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Signal Transduction; Vemurafenib
PubMed: 30782032
DOI: 10.1080/17474086.2019.1583553 -
Leukemia & Lymphoma Jun 2011Hairy cell leukemia (HCL) is a disease with distinctive clinical findings, as well as a unique morphology and immunophenotype. These features typically allow for a... (Review)
Review
Hairy cell leukemia (HCL) is a disease with distinctive clinical findings, as well as a unique morphology and immunophenotype. These features typically allow for a reliable and reproducible diagnosis in nearly all situations. However, certain morphological features of HCL, such as villous cytoplasmic projections or characteristic tissue specific infiltrative patterns, including red pulp expansion with pseudosinuses, may be seen in other B-cell lymphoproliferative disorders. A methodical and thorough approach evaluating the clinical, cytological, histological, architectural, and immunophenotypic features is described and will aid in rendering the appropriate diagnosis. This is paramount as current data indicate that hairy cell leukemia - variant and other splenic B-cell lymphomas must be distinguished from HCL, as the response to therapy differs in these disorders.
Topics: Bone Marrow; Diagnosis, Differential; Humans; Leukemia, Hairy Cell; Lymph Nodes; Lymphoma, B-Cell
PubMed: 21417827
DOI: 10.3109/10428194.2011.565435 -
Cancer Reports (Hoboken, N.J.) Mar 2022Hairy cell leukemia (HCL) is a rare chronic B-cell neoplasm with good long-term prognosis. First and second-line therapies include purine nucleoside analogues (PNAs) and...
BACKGROUND
Hairy cell leukemia (HCL) is a rare chronic B-cell neoplasm with good long-term prognosis. First and second-line therapies include purine nucleoside analogues (PNAs) and rituximab, but until recently, limited alternative options were available for patients with two or more relapses.
AIM
The aim of this study is to describe our real-life experience with HCL patients in third and fourth-line therapies.
METHODS AND RESULTS
Data from 49 HCL patients with two or more relapses, including 16 patients with three or more relapses, were collected from the French retrospective HCL cohort covering the period from 1980 until 2011. They were analyzed to assess hematological response, relapse free survival (RFS) and overall survival (OS) after third (L3) and fourth line (L4). The median age at diagnosis was 53 years. PNAs were the most frequently used treatments. As L3 therapy, 29 patients received PNAs (66%) and 15 (34%) other treatments (rituximab [11%] or interferon [7%] alone or in combination [16%]). The distribution of L4 treatments was similar. The overall hematological response rate (OHRR) after L3 was 97% (complete hematological response 86%) with a 40% five-year cumulative incidence of relapse (CIR), a median RFS of 104 months, and a median OS of 235 months. After L4, the OHRR was 94% with a two-year CIR of fourth relapse of 27%. Eleven secondary cancers (5-year cumulative incidence of 12%) were diagnosed in 10 patients. Patients with ≥2 relapses experience frequent further relapses, with increasingly shorter time to next treatment as the number of treatment lines increases. Furthermore, treatment strategies are associated with substantial toxicities.
CONCLUSION
All these points lead to the need for novel treatments.
Topics: Humans; Leukemia, Hairy Cell; Peptide Nucleic Acids; Recurrence; Retrospective Studies; Rituximab
PubMed: 34250762
DOI: 10.1002/cnr2.1495 -
Annals of Hematology Mar 2021Skin lesions have been reported in about 10-12% of hairy cell leukemia (HCL) patients. Most are etiologically related to autoimmune or infectious processes, although... (Review)
Review
Skin lesions have been reported in about 10-12% of hairy cell leukemia (HCL) patients. Most are etiologically related to autoimmune or infectious processes, although secondary cutaneous neoplasms and drug-induced lesions are also reported. However, leukemia cutis with the direct infiltration of the skin by leukemic cells is extremely rare in HCL patients. This paper reviews the epidemiology, pathogenesis, clinical symptoms, diagnosis, and approach to treating skin lesions in HCL. A literature review of the MEDLINE database for articles in English concerning hairy cell leukemia, skin lesions, leukemia cutis, adverse events, infectious, cutaneous, drug reactions, neutrophilic dermatoses, secondary neoplasms, and vasculitis was conducted via PubMed. Publications from January 1980 to September 2020 were scrutinized. Additional relevant publications were obtained by reviewing the references from the chosen articles.
Topics: Humans; Leukemia, Hairy Cell; Leukemic Infiltration; Skin; Skin Diseases; Skin Neoplasms; Vasculitis
PubMed: 33216198
DOI: 10.1007/s00277-020-04349-z -
Journal of Clinical Oncology : Official... Mar 2017Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with unique clinicopathologic features and an initial exquisite sensitivity to chemotherapy with purine... (Review)
Review
Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with unique clinicopathologic features and an initial exquisite sensitivity to chemotherapy with purine analogs; however, the disease relapses, often repeatedly. The enigmatic pathogenesis of HCL was recently clarified by the discovery of its underlying genetic cause, the BRAF-V600E kinase-activating mutation, which is somatically and clonally present in almost all patients through the entire disease spectrum and clinical course. By aberrantly activating the RAF-MEK-ERK signaling pathway, BRAF-V600E shapes key biologic features of HCL, including its specific expression signature, hairy morphology, and antiapoptotic behavior. Accompanying mutations of the KLF2 transcription factor or the CDKN1B/p27 cell cycle inhibitor are recurrent in 16% of patients with HCL and likely cooperate with BRAF-V600E in HCL pathogenesis. Conversely, BRAF-V600E is absent in other B-cell neoplasms, including mimickers of HCL that require different treatments (eg, HCL-variant and splenic marginal zone lymphoma). Thus, testing for BRAF-V600E allows for a genetics-based differential diagnosis between HCL and HCL-like tumors, even noninvasively in routine blood samples. BRAF-V600E also represents a new therapeutic target. Patients' leukemic cells exposed ex vivo to BRAF inhibitors are spoiled of their HCL identity and then undergo apoptosis. In clinical trials of patients with HCL who have experienced multiple relapses after purine analogs or who are refractory to purine analogs, a short course of the oral BRAF inhibitor vemurafenib produced an almost 100% response rate, including complete remission rates of 35% to 42%, without myelotoxicity. To further improve on these results, it will be important to clarify the mechanisms of incomplete leukemic cell eradication by vemurafenib and to explore chemotherapy-free combinations of a BRAF inhibitor with other targeted agents (eg, a MEK inhibitor and/or an anti-CD20 monoclonal antibody).
Topics: Animals; Genomics; Humans; Leukemia, Hairy Cell
PubMed: 28297625
DOI: 10.1200/JCO.2016.71.1556 -
Leukemia & Lymphoma Jun 2011Hairy cell leukemia (HCL) cells accumulate and proliferate in the spleen and the bone marrow. In these tissue compartments, HCL cells interact with accessory cells,... (Review)
Review
Hairy cell leukemia (HCL) cells accumulate and proliferate in the spleen and the bone marrow. In these tissue compartments, HCL cells interact with accessory cells, matrix proteins, and various cyctokines, collectively referred to as the 'microenvironment.' Surface receptors expressed on HCL cells and respective stromal ligands are critical for this cross-talk between HCL cells and the microenvironment. Chemokine receptors, adhesion molecules (integrins, CD44), the B cell antigen receptor (BCR), and CD40, expressed on the HCL cells, are likely to be critical for homing, retention, survival, and expansion of the neoplastic B cells. Some of these pathways are now targeted in first clinical trials in other mature B-cell malignancies. We summarize key aspects of the cellular and molecular interactions between HCL cells and their microenvironment. Also, we outline future prospects for therapeutic targeting of the microenvironment in HCL, focusing on CXCR4 and kinase inhibitors (Syk, Btk, phosphatidylinositol 3-kinase [PI3K]) that target B cell receptor signaling.
Topics: Cell Adhesion Molecules; Humans; Leukemia, Hairy Cell; Receptors, Antigen, B-Cell; Receptors, Chemokine; T-Lymphocytes; Tumor Microenvironment
PubMed: 21438839
DOI: 10.3109/10428194.2011.568649 -
American Journal of Hematology Dec 2017Hairy 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...
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 poor prognosis RISK ADAPTED THERAPY: Purine analogs (PNA) are indicated in symptomatic first line HCL patients. The use of PNA followed by rituximab represents an alternative option.
MANAGEMENT OF PROGRESSIVE OR REFRACTORY DISEASE
It is based on the use of BRAF inhibitors associated or not with MEK inhibitors, recombinant immunoconjugates targeting CD22 or BCR inhibitors.
Topics: Disease Management; Disease Progression; Humans; Immunoconjugates; Immunophenotyping; Leukemia, Hairy Cell; Proto-Oncogene Proteins B-raf; Risk Assessment; Salvage Therapy; Sialic Acid Binding Ig-like Lectin 2
PubMed: 29110361
DOI: 10.1002/ajh.24936 -
Clinical Advances in Hematology &... Mar 2018Hairy cell leukemia (HCL) is a chronic B-cell malignancy with multiple treatment options, including several that are investigational. Patients present with pancytopenia... (Review)
Review
Hairy cell leukemia (HCL) is a chronic B-cell malignancy with multiple treatment options, including several that are investigational. Patients present with pancytopenia and splenomegaly, owing to the infiltration of leukemic cells expressing CD22, CD25, CD20, CD103, tartrate-resistant acid phosphatase (TRAP), annexin A1 (ANXA1), and the BRAF V600E mutation. A variant lacking CD25, ANXA1, TRAP, and the BRAF V600E mutation, called HCLv, is more aggressive and is classified as a separate disease. A molecularly defined variant expressing unmutated immunoglobulin heavy variable 4-34 (IGHV4-34) is also aggressive, lacks the BRAF V600E mutation, and has a phenotype of HCL or HCLv. The standard first-line treatment, which has remained unchanged for the past 25 to 30 years, is single-agent therapy with a purine analogue, either cladribine or pentostatin. This approach produces a high rate of complete remission. Residual traces of HCL cells, referred to as minimal residual disease, are present in most patients and cause frequent relapse. Repeated treatment with a purine analogue can restore remission, but at decreasing rates and with increasing cumulative toxicity. Rituximab has limited activity as a single agent but achieves high complete remission rates without minimal residual disease when combined with purine analogues, albeit with chemotherapy-associated toxicity. Investigational nonchemotherapy options include moxetumomab pasudotox, which targets CD22; vemurafenib or dabrafenib, each of which targets the BRAF V600E protein; trametinib, which targets mitogen-activated protein kinase enzyme (MEK); and ibrutinib, which targets Bruton tyrosine kinase (BTK).
Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Biopsy; Clinical Decision-Making; Humans; Immunohistochemistry; Immunophenotyping; Leukemia, Hairy Cell; Molecular Targeted Therapy; Neoplasm, Residual; Standard of Care; Treatment Outcome
PubMed: 29742076
DOI: No ID Found -
Blood Mar 2023
Topics: Humans; Leukemia, Hairy Cell; Proto-Oncogene Proteins B-raf; Salvage Therapy; Mutation
PubMed: 36862436
DOI: 10.1182/blood.2022018319 -
NEJM Evidence Oct 2023Vemurafenib and Obinutuzumab for Hairy Cell LeukemiaIn this study of vemurafenib plus obinutuzumab of patients with previously untreated hairy cell leukemia, treatment...
Vemurafenib and Obinutuzumab for Hairy Cell LeukemiaIn this study of vemurafenib plus obinutuzumab of patients with previously untreated hairy cell leukemia, treatment was administered for four cycles, and the primary end point was complete remission rate. Twenty-seven of 30 patients completed all four cycles of treatment and achieved complete remission. No dose-limiting toxicity was observed.
Topics: Humans; Vemurafenib; Leukemia, Hairy Cell; Antibodies, Monoclonal, Humanized; Remission Induction
PubMed: 38320179
DOI: 10.1056/EVIDoa2300074