-
Leukemia & Lymphoma Dec 2019Hairy cell leukemia (HCL) is an indolent B-cell malignancy, with long-term responses to purine analogs, but with decreasing efficacy and increasing toxicity with... (Review)
Review
Hairy cell leukemia (HCL) is an indolent B-cell malignancy, with long-term responses to purine analogs, but with decreasing efficacy and increasing toxicity with repeated courses. Leukemic cells express CD22, CD20, CD25, tartrate-resistant acid phosphatase (TRAP), annexin 1A (Anxa1), and BRAF V600E mutation. HCLv, lacking CD25, Anxa1, TRAP, and BRAF V600E, is more aggressive and less purine analog-sensitive. A molecularly defined IGHV4-34+ variant is also resistant whether HCL or HCLv immunophenotypically. Traces of HCL cells, termed minimal residual disease (MRD), accompany most with complete remission (CR) and may cause relapse. Rituximab has limited single-agent activity, but frequent CR without MRD when combined with purine analog, albeit with chemotherapy toxicities. The anti-CD22 recombinant immunotoxin Moxetumomab Pasudotox can achieve MRD-negative CR in multiply relapsed HCL without chemotherapy toxicities and was FDA approved in 2018 as Lumoxiti. Investigational oral non-chemotherapy options also include Vemurafenib or Dabrafenib/Trametinib targeting BRAF V600E ± MEK, and Ibrutinib targeting Bruton's tyrosine kinase.
Topics: Algorithms; Biomarkers; Clinical Decision-Making; Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Disease Susceptibility; Humans; Leukemia, Hairy Cell; Treatment Outcome
PubMed: 31068044
DOI: 10.1080/10428194.2019.1608536 -
American Journal of Hematology Feb 2022Hairy 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 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 Bruton Tyrosine 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.
Topics: Antigens, CD; Antineoplastic Agents; Disease Management; Disease Progression; Humans; Immunoconjugates; Immunotherapy; Leukemia, Hairy Cell; Prognosis; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Risk Assessment; Risk Factors
PubMed: 34710243
DOI: 10.1002/ajh.26390 -
American Journal of Hematology Dec 2019Hairy 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... (Review)
Review
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. They are 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 three or four based on the CD11C, CD103, CD123, and CD25 expression. Also, 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. The VH4-34 positive HCL cases are associated with poor prognosis.
TREATMENT
Risk adapted therapy with purine nucleoside 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 is based on the use of BRAF inhibitors associated or not with MEK inhibitors, recombinant immunoconjugates targeting CD22 or BCR inhibitors.
Topics: Algorithms; Antimetabolites, Antineoplastic; B-Lymphocytes; Biopsy; Bone Marrow Examination; Cladribine; Humans; Immunophenotyping; Immunotoxins; Leukemia, Hairy Cell; Middle Aged; Mutation, Missense; Neoplasm Proteins; Neoplasms, Second Primary; Neoplastic Stem Cells; Point Mutation; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Risk Assessment; Rituximab; Salvage Therapy
PubMed: 31591741
DOI: 10.1002/ajh.25653 -
Current Oncology Reports Aug 2023This article summarizes the current state of knowledge of hairy cell leukemia (HCL) regarding presentation, diagnosis, therapy, and monitoring, including perspectives on... (Review)
Review
PURPOSE OF REVIEW
This article summarizes the current state of knowledge of hairy cell leukemia (HCL) regarding presentation, diagnosis, therapy, and monitoring, including perspectives on emergent therapies.
RECENT FINDINGS
Over the past decade, there has been enormous progress in the understanding of the biology of HCL which has led to the development of novel therapeutic strategies. The maturation of data regarding existing management strategies has also lent considerable insight into therapeutic outcomes and prognosis of patients treated with chemo- or chemoimmunotherapy. Purine nucleoside analogs remain the cornerstone of treatment, and the addition of rituximab has deepened and prolonged responses in the upfront and relapsed setting. Targeted therapies now have a more defined role in the management of HCL, with BRAF inhibitors now having a potential in the first-line setting in selected cases as well as in relapse. Next-generation sequencing for the identification of targetable mutations, evaluation of measurable residual disease, and risk stratification continue to be areas of active investigation. Recent advances in HCL have led to more effective therapeutics in the upfront and relapsed setting. Future efforts will focus on identifying patients with high-risk disease who require intensified regimens. Multicenter collaborations are the key to improving overall survival and quality of life in this rare disease.
Topics: Humans; Leukemia, Hairy Cell; Antineoplastic Agents; Quality of Life; Rituximab; Prognosis; Multicenter Studies as Topic
PubMed: 37097545
DOI: 10.1007/s11912-023-01419-z -
Blood Feb 2017Hairy cell leukemia is an uncommon hematologic malignancy characterized by pancytopenia and marked susceptibility to infection. Tremendous progress in the management of...
Hairy cell leukemia is an uncommon hematologic malignancy characterized by pancytopenia and marked susceptibility to infection. Tremendous progress in the management of patients with this disease has resulted in high response rates and improved survival, yet relapse and an appropriate approach to re-treatment present continuing areas for research. The disease and its effective treatment are associated with immunosuppression. Because more patients are being treated with alternative programs, comparison of results will require general agreement on definitions of response, relapse, and methods of determining minimal residual disease. The development of internationally accepted, reproducible criteria is of paramount importance in evaluating and comparing clinical trials to provide optimal care. Despite the success achieved in managing these patients, continued participation in available clinical trials in the first-line and particularly in the relapse setting is highly recommended. The Hairy Cell Leukemia Foundation convened an international conference to provide common definitions and structure to guide current management. There is substantial opportunity for continued research in this disease. In addition to the importance of optimizing the prevention and management of the serious risk of infection, organized evaluations of minimal residual disease and treatment at relapse offer ample opportunities for clinical research. Finally, a scholarly evaluation of quality of life in the increasing number of survivors of this now manageable chronic illness merits further study. The development of consensus guidelines for this disease offers a framework for continued enhancement of the outcome for patients.
Topics: Antineoplastic Agents; Cladribine; Disease Management; Humans; Leukemia, Hairy Cell; Neoplasm Recurrence, Local; Neoplasm, Residual; Pentostatin; Treatment Outcome
PubMed: 27903528
DOI: 10.1182/blood-2016-01-689422 -
Blood Reviews Jan 2022Hairy cell leukemia (HCL) is an indolent B-cell malignancy, usually driven by the BRAF V600E mutation. For 30 years, untreated and relapsed HCL was successfully treated... (Review)
Review
Hairy cell leukemia (HCL) is an indolent B-cell malignancy, usually driven by the BRAF V600E mutation. For 30 years, untreated and relapsed HCL was successfully treated with purine analogs, but minimal residual disease (MRD) remained in most patients, eventually causing relapse. Repeated purine analogs achieve decreasing efficacy and increasing toxicity, particularly to normal T-cells. MRD-free complete remissions (CRs) are more common using rituximab with purine analogs in both 1-line and relapsed settings. BRAF inhibitors and Ibrutinib can achieve remission, but due to persistence of MRD, must be used chronically to prevent relapse. BRAF inhibition combined with Rituximab can achieve high MRD-free CR rates. Anti-CD22 recombinant immunotoxin moxetumomab pasudotox is FDA-approved in the relapsed setting and is unique in achieving high MRD-free CR rates as a single-agent. Avoiding chemotherapy and rituximab may be important in ensuring both recovery from COVID-19 and successful COVID-19 vaccination, an area of continued investigation.
Topics: Antineoplastic Agents; COVID-19; Humans; Leukemia, Hairy Cell; Neoplasm, Residual; Pandemics; Proto-Oncogene Proteins B-raf; Purines; Recurrence; Rituximab
PubMed: 34535326
DOI: 10.1016/j.blre.2021.100888 -
Best Practice & Research. Clinical... Dec 2015This brief review highlights the sequence of therapeutic milestones and advances in our understanding of the biology of hairy cell leukemia (HCL) with a focus on recent... (Review)
Review
This brief review highlights the sequence of therapeutic milestones and advances in our understanding of the biology of hairy cell leukemia (HCL) with a focus on recent molecular findings and how these may be applied to improve disease outcomes in the future. Targeted therapy is discussed in the context of the recently identified BRAF mutation and other genetic findings.
Topics: Antineoplastic Agents; B-Lymphocytes; Cladribine; Disease Management; History, 20th Century; History, 21st Century; Humans; Immunotoxins; Indoles; Leukemia, Hairy Cell; Mutation; Pentostatin; Proto-Oncogene Proteins B-raf; Remission Induction; Rituximab; Splenectomy; Sulfonamides; Survival Analysis; Vemurafenib
PubMed: 26614906
DOI: 10.1016/j.beha.2015.10.015 -
Current Opinion in Hematology Jul 2015In this review, we discuss the pathogenesis and standard therapeutic approach to hairy cell leukaemia (HCL) as well as newer targeted therapies under investigation... (Review)
Review
PURPOSE OF REVIEW
In this review, we discuss the pathogenesis and standard therapeutic approach to hairy cell leukaemia (HCL) as well as newer targeted therapies under investigation showing promising end-points in treating HCL.
RECENT FINDINGS
HCL is an indolent B-cell leukaemia. Historically, HCL patients have achieved excellent response to purine nucleoside analogues and single purine analogue treatment with pentostatin or cladribine is currently the standard of care for initial treatment. Most patients achieve complete remission with this form of therapy. However, long-term follow-up has demonstrated that a large number of patients eventually develop relapsed disease. Relapse disease tends to be more difficult to treat and refractory to the same purine analogues. Development of relapsing and refractory disease after initially achieving complete remission with purine analogue treatment has generated a need for alternative therapies.
SUMMARY
Identification of the BRAFV600E mutation in nearly 100% of HCL patients has provided rationale for inclusion of BRAF inhibitors into the therapeutic armamentarium to treat HCL. Clinical trials are currently underway measuring efficacy of vemurafenib in achieving clinical response in relapsed/refractory HCL and also toxicity. Other novel therapies with monoclonal and immunotoxin-conjugated antibodies have also shown promising response in recent investigational studies.
Topics: Antineoplastic Agents; B-Lymphocytes; Cladribine; Clinical Trials as Topic; Gene Expression; Humans; Imidazoles; Indoles; Leukemia, Hairy Cell; Mutation; Oximes; Pentostatin; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Recurrence; Remission Induction; Sulfonamides; Vemurafenib
PubMed: 26049757
DOI: 10.1097/MOH.0000000000000154 -
Blood Advances Jul 2022
Topics: COVID-19; Humans; Leukemia, Hairy Cell
PubMed: 35500220
DOI: 10.1182/bloodadvances.2022007357 -
Blood Reviews Sep 2014Hairy cell leukemia was initially described as a clinicopathologic entity more than 50 years ago. We have subsequently discovered that HCL is really at least two... (Review)
Review
Hairy cell leukemia was initially described as a clinicopathologic entity more than 50 years ago. We have subsequently discovered that HCL is really at least two diseases: classical HCL and the hairy cell leukemia variant. The former is among a small group of cancers exceptional for being (nearly) unified by a single genetic lesion, the BRAF V600E mutation. Over the past three decades, tremendous progress in both diagnostic and prognostic clarification has been accompanied by therapeutic advances in classical HCL. Consequently, this once uniformly fatal disease has been converted in most cases into a chronic illness enabling patients to live long and productive lives. In response to standard therapy, patients have high complete remission rates. Unfortunately, the long-term survival curves have not plateaued, revealing that this disease is controlled but not cured. Though rare and representing only about 10% of an already rare disease, those patients with the variant fare exceptionally poorly with standard therapy: complete response rates to purine nucleoside analogs are reported to be less than 50%, whereas the complete response rates in classical HCL are up to 90%. Novel small molecules targeting BRAF and the B-cell receptor signaling complex, and biologic agents like antibodies and immunotoxin conjugates are being explored for those patients who have relapsed. Substantial opportunities for continued research remain. This complex and multi-faceted disease incorporates challenges from altered immunity associated with the underlying disease and its treatments. Considering the rarity of this malignancy, optimization of patient management requires multi-institutional collaboration. The Hairy Cell Leukemia Foundation (www.hairycellleukemia.org) was formed to coordinate these efforts.
Topics: Biomedical Research; Disease Management; Humans; Immunophenotyping; Infections; Leukemia, Hairy Cell; Molecular Diagnostic Techniques
PubMed: 25110197
DOI: 10.1016/j.blre.2014.06.003