Hairy cell leukemia is an indolent, low-grade, B-cell lymphoma usually characterized by the following:
In addition to the B-cell antigens CD19, CD20, and CD22, the cells coexpress CD11c, CD25, and CD103. The BRAF-V600E mutation is a hairy cell leukemia–defining genetic lesion that can be used diagnostically.[1,2] The decision to treat is based on symptomatic cytopenias, massive splenomegaly, or the presence of other complications. About 10% of all patients will never require therapy.
No generally accepted staging system is useful for both prognosis and therapy.
Untreated hairy cell leukemia is characterized by splenomegaly, varying degrees of leukopenia (occasionally leukocytosis) and/or pancytopenia, and bone marrow infiltration by an atypical cell with prominent cytoplasmic projections (i.e., hairy cells). The bone marrow is usually fibrotic and is not easily aspirated. Although a bone marrow biopsy may be required for enrollment in a clinical trial, the leukemia diagnosis can usually be obtained by flow cytometry.
After the initiation of treatment with cladribine, pentostatin, or recombinant interferon alfa, the survival rate of patients with advanced hairy cell leukemia appears to be higher than 85% after 5 years of follow-up.
Prior to the COVID-19 (SARS-CoV-2) pandemic, the standard initial therapy for patients with hairy cell leukemia was infusion of cladribine daily for 5 days, given with or without eight weekly doses of rituximab.[1,2,3] However, treatment with a purine analogue-based regimen leads to significant and prolonged neutropenia and impairment of T-cell function, both problematic during the pandemic in terms of fighting viral infection and establishing vaccination-induced immunity. The Hairy Cell Leukemia Foundation convened a virtual meeting of 39 experts from around the world to amend 2017 consensus recommendations. The adapted treatment guidelines, published in 2021, are based primarily on anecdotal experience and expert opinion.[Level of evidence: 3iiiDiv] The adapted treatment guidelines can be summarized as follows:
Hairy cell leukemia is rare, with only 600 to 800 new cases annually in the United States. Given the low incidence, these expert recommendations based on anecdotal experience heavily influence the choice of therapeutic options as controlled trials for this indolent leukemia cannot be completed expeditiously.
Hairy cell leukemia is highly treatable but rarely cured. Because it is easily controlled, many patients have prolonged survival with the use of sequential therapies. The decision to treat is based on cytopenias (especially if symptomatic), increasing splenomegaly, indications that the disease is progressing, or the presence of other, usually infectious complications. It is reasonable to offer no therapy if the patient is asymptomatic and if blood counts are maintained in an acceptable range. During the COVID-19 (SARS-CoV-2) pandemic, some options for initial standard therapy, including cladribine or pentostatin, have been replaced in favor of other options with less toxicity, but these options also elicit less-durable responses.
Treatment options for hairy cell leukemia include the following:
Rituximab can induce durable complete remissions with minimal toxic effects in patients with multiple relapsing or refractory disease after purine analogue therapy or after treatment with interferon.[1,2,3,4,5][Level of evidence: 3iiiDiv]
Vemurafenib With or Without Rituximab
The BRAF-V600E mutation occurs in almost 100% of patients with classic-form hairy cell leukemia and almost never in patients with other B-cell lymphomas and leukemias, including hairy cell leukemia variants.[Level of evidence: 3iiiDiv] Vemurafenib can be given in combination with rituximab.
Evidence (vemurafenib with or without rituximab):
Recombinant Interferon Alfa
Recombinant interferon alfa given subcutaneously three times per week for 1 year yields a 10% complete response rate and an 80% overall response rate. The drug frequently produces an influenza-like syndrome early in the course of treatment. Late effects include depression and lethargy. Responding patients who relapse usually react positively to re-treatment with recombinant interferon alfa. Remission can be prolonged with a low-dose maintenance regimen.
Evidence (recombinant interferon alfa):
Evidence (moxetumomab pasudotox-tdfk):
Cladribine With or Without Rituximab
Cladribine given intravenously by daily subcutaneous injections, or by 2-hour infusions daily for 5 to 7 days results in a complete response rate of 50% to 80% and an overall response rate of 85% to 95%.[19,20,21][Level of evidence: 3iiiDiv] The response rate was lower in 979 patients treated with the Group C mechanism of the National Cancer Institute (i.e., 50% complete remission rate, 37% partial remission rate). Responses are durable with this short course of therapy, and patients who relapse often respond to re-treatment with cladribine.[22,23,24]
Evidence (cladribine with or without rituximab):
MRD testing in this setting has never been validated as a clinically significant end point. This concept requires further study, but hairy cell leukemia is rare, with only 600 to 800 new cases annually in the United States.
Pentostatin given intravenously every other week for 3 to 6 months produces a 50% to 76% complete response rate and an 80% to 87% overall response rate.[12,28] Complete remissions are of substantial duration.
Re-treatment With Cladribine or Pentostatin
Patients with hairy cell leukemia who relapse after the first course of cladribine or pentostatin often respond well to re-treatment with the same or another purine analogue, especially if relapse occurs after 2 years.[24,28,31,32,33,34][Level of evidence: 3iiiDiv]
Splenectomy will partially or completely normalize the peripheral blood in most patients with hairy cell leukemia. Usually little or no change occurs in the bone marrow after splenectomy, and virtually all patients have progressive disease within 12 to 18 months. Therefore, because a number of more effective alternatives are available, splenectomy plays a decreasing role in the treatment of this disease.
Current Clinical Trials
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Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of hairy cell leukemia. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
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PDQ® Adult Treatment Editorial Board. PDQ Hairy Cell Leukemia Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/leukemia/hp/hairy-cell-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389184]
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Last Revised: 2022-01-14
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