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Home > Health Library > Hairy Cell Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI]
This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
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; therefore, bone marrow biopsies are required for diagnosis and evaluation of the degree of hairy cell infiltration.
After the initiation of treatment with cladribine (2-chlorodeoxyadenosine, 2-CdA), pentostatin, or interferon-alpha, the survival rate of patients with advanced hairy cell leukemia appears to be higher than 85% at 5 years' follow-up.
The initial therapies of choice for hairy cell leukemia are either cladribine (2-chlorodeoxyadenosine, 2-CdA) or pentostatin.[1,2] These drugs have comparable response rates but have not been compared in phase III trials. Cladribine is administered as a one-time continuous infusion or series of subcutaneous injections and is associated with a high rate of febrile neutropenia.[3,4,5,6] Rarely, more than one course of treatment is required to induce a desirable response. Treatment should be discontinued once complete remission or stable partial remission with normalization of peripheral blood counts is reached. The presence of residual disease may be predictive of relapse but does not seem to affect survival.[5,7]
The role of consolidation or maintenance therapy in preventing relapse or progression of the disease after treatment with purine analogs has not been evaluated and remains unproven. Pentostatin is administered intermittently for a longer time but may result in a lower incidence of febrile complications.[8,9] While most patients remain disease free 10 years after treatment with these purine analogs, no patient has been monitored long enough to assess cure.[10,11] Both nucleoside analogs cause profound suppression of CD4 counts, which may last for a year, and a potential increased risk of second malignancies has been reported.[5,12]
A study of 3,104 survivors of hairy cell leukemia from the Surveillance, Epidemiology, and End Results (SEER) database showed an increased risk of second cancers (standardized incidence ratio, 1.24; 95% confidence interval, 1.11–1.37), especially for Hodgkin and non-Hodgkin lymphomas. The increased risk for second cancers was seen even in the two decades before the introduction of purine nucleosides. With the use of cladribine, an increased risk of second malignancies is possible among patients with hairy cell leukemia (observed to expected ratio of about 1.8 in several series after 6 years).[5,12] Several series using pentostatin did not report an increased risk of second malignancies.[8,10,14] For a few patients, such as those with severe thrombocytopenia, splenectomy might be considered. After splenectomy, 50% of patients will require no additional therapy, and long-term survivors are common. Therapy with interferon-alpha is another treatment option, especially for patients with intercurrent infection.[9,16]
The hairy cell leukemia variant has a distinctive phenotype and typically presents with leukocytosis instead of leukopenia.[17,18] Patients with this variant have poorer responses to initial cladribine, have shorter durations of response, and typically do not respond again to purine analogs after relapse. Combinations of rituximab and purine analogs are under evaluation, and further studies are required to define optimal therapies.
Hairy cell leukemia is a highly treatable disease. Because it is easily controlled, many patients have prolonged survival with 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.
Standard Treatment Options for Hairy Cell Leukemia
Standard treatment options for hairy cell leukemia include the following:
Cladribine with or without rituximab
Cladribine (2-chlorodeoxyadenosine, 2-CdA) 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%.[1,2,3][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.[4,5,6]
Evidence (cladribine with or without rituximab):
MRD testing in this setting has never been validated as a clinically significant endpoint. This concept requires further study, but hairy cell leukemia is rare, with 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.[10,11] Complete remissions are of substantial duration.
Interferon-alpha given subcutaneously 3 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 interferon-alpha. Remission can be prolonged with a low-dose maintenance regimen.
Splenectomy will partially or completely normalize the peripheral blood in the vast majority of 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 is playing a decreasing role in the treatment of this disease.
Current Clinical Trials
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Treatment Options for Relapsed or Refractory Hairy Cell Leukemia
Treatment options for relapsed or refractory hairy cell leukemia include the following:
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 analog, especially if relapse occurs after 2 years.[1,2,3,4,5,6][Level of evidence: 3iiiDiv]
Rituximab can induce durable complete remissions with minimal toxic effects in patients with multiple relapsing or refractory disease after purine analog therapy or after treatment with interferon.[7,8,9,10,11][Level of evidence: 3iiiDiv]
Purine analog plus rituximab
Combinations or the sequential use of rituximab with either cladribine or pentostatin are effective in achieving complete remission and are under clinical evaluation.[12,13,14,15][Level of evidence: 3iiiDiv]
Vemurafenib with or without rituximab
The BRAF-V600E mutation occurs in almost 100% of classic-form hairy cell leukemia patients and almost never in 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):
Moxetumomab pasudotox-tdfk is an anti-CD22 recombinant immunotoxin that was approved by the U.S. Food and Drug Administration to treat patients with relapsed or refractory disease.[19,20,21,22]
Evidence (moxetumomab pasudotox-tdfk):
Interferon-alpha and splenectomy are therapeutic options that can be considered when other options have been exhausted (Refer to the section on Interferon-alpha in the Standard Treatment Options for Hairy Cell Leukemia section.)[25,26,27][Level of evidence: 3iiiDiv].
Interferon-alpha and splenectomy are therapeutic options that can be considered when other options have been exhausted.[Level of evidence: 3iiiDiv]
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Treatment Options for Hairy Cell Leukemia
Added text to state that in a randomized phase II study, 68 patients with previously untreated hairy cell leukemia were randomly assigned to receive cladribine 0.15 mg/kg intravenously on days 1 to 5 with 8 weekly doses of rituximab concurrently or after 6 months if still positive with minimal residual disease (MRD) testing. With a median follow-up of 96 months, 94% of patients who received concurrent therapy were MRD-free compared with 12% of patients who received delayed therapy [cited Chihara et al. as reference 9 and level of evidence 3iiiDiv).
Added text to state that MRD testing in this setting has never been validated as a clinically significant endpoint; this concept requires further study, but hairy cell leukemia is rare, with 600 to 800 new cases annually in the United States.
Relapsed or Refractory Hairy Cell Leukemia
Revised text to state that 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 analog, especially if relapse occurs after 2 years.
Added text to state that vemurafenib can be given in combination with rituximab.
Added moxetumomab pasudotox-tdfk as a new subsection.
Added text to state that in a phase II study, reported in abstract form, 28 patients with refractory hairy cell leukemia had a 48% response rate to ibrutinib (cited Jones et al. as reference 24 and level of evidence: 3iiiDiv).
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
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 who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Hairy Cell Leukemia Treatment are:
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Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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The preferred citation for this PDQ summary is:
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: 2020-12-17
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