Hairy Cell Leukemia 

Updated: Sep 16, 2018
Author: Emmanuel C Besa, MD; Chief Editor: Koyamangalath Krishnan, MD, FRCP, FACP 

Overview

Practice Essentials

Hairy cell leukemia (HCL) is a chronic lymphoid leukemia, originally described in 1958 by Bouroncle and colleagues[1, 2]  and named after the hairlike cytoplasmic projections seen on the surface of the abnormal B-cells (see the image below).

Blood film at × 1000 magnification. This image dem Blood film at × 1000 magnification. This image demonstrates lymphocytes with characteristic cytoplasmic projections. Photographed by U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.

See Chronic Leukemias: 4 Cancers to Differentiate, a Critical Images slideshow, to help detect chronic leukemias and determine the specific type present.

Hairy cell leukemia is recognized as a clonal B-cell malignancy, as identified by immunoglobulin gene rearrangements that result in a phenotype B-cell expression of surface antigens. These reflect the differentiation between the immature B-cell of chronic lymphocytic leukemia and the plasma cell of multiple myeloma. 

For patient education information, see the Cancer Center, as well as Leukemia.

Pathophysiology

The abnormal cell in hairy cell leukemia (HCL) is a clonal B-cell lymphocyte (see image below). This cell infiltrates the reticuloendothelial system and interferes with bone marrow function, resulting in bone marrow failure or pancytopenia.[3, 4] The hairy cell also infiltrates the liver and spleen, resulting in organomegaly.

Blood film at × 400 magnification. This image demo Blood film at × 400 magnification. This image demonstrates a lymphocytosis and an absence of any other type of blood cell (pancytopenia). The characteristic cytoplasmic projections are already visible. Photographed by U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.

The pathogenesis of HCL was 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.[5] 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.[6]  

The etiology of HCL has not been determined, although some investigators suggest that exposures to benzene, organophosphorus insecticides, or other solvents may be related to disease development. This hypothesis has not been confirmed by other reports, although a French study that evaluated occupational exposure to pesticides and lymphoid neoplasms in men appears to support the hypothesis that occupational pesticide exposures may not only be involved in HCL, Hodgkin lymphoma, and multiple myeloma, but also may play a role in non-Hodgkin lymphoma.[7] Further research is needed.

Other suggested etiologic associations include exposure to radiation, agricultural chemicals, and wood dust, and a previous history of infectious mononucleosis.

Overexpression of cyclin D1 protein, an important cell-cycle regulator, has been observed in HCL and may play a role in the molecular pathogenesis of the disease.

Accumulation of hairy cells in the bone marrow, liver, and spleen, with very little lymph node involvement, is characteristic of HCL. This pattern probably results from the expression of the integrin receptor alpha4-beta1 by the hairy cells and the interaction of the receptor with the vascular adhesion molecule-1 (VCAM-1) found in splenic and hepatic endothelia, bone marrow, and splenic stroma.

Epidemiology

Hairy cell leukemia is relatively uncommon, accounting for 2% of all leukemia cases. An estimated 1100 new cases were diagnosed in the United States in 2016.[8] Hairy cell leukemia is observed more commonly in whites. It has been reported to occur in Ashkenazi Jews, and it is rare in Japan and in those of African descent.

The disease occurs predominantly in middle-aged men, with a median age of 49-51 years. The male-to-female ratio is 4:1 to 5:1.[2, 9]

Prognosis

Hairy cell leukemia behaves like a chronic leukemia. With treatment, most patients achieve clinical remissions and, sometimes, long-term cures. In the United States, 5-year survival ranged from 84% to 94% (lower in blacks than whites).[8]

The risk of second malignancies has been observed in patients with hairy cell leukemia, either through the disease itself or secondary to the immunosuppressive effects of the therapy. Skin cancers (ie, melanoma and non-melanoma) are the most common, representing 33-36% of all secondary malignancies. Other malignancies include prostate cancers, gastrointestinal malignancies, non-Hodgkin lymphomas, and ovarian, cervical, and breast cancer.[10]

A 20-year follow-up in 117 patients in British Columbia showed that 31% developed a second malignancy, of which 30% were diagnosed before hairy cell leukemia was found.[11]  On the other hand, an MD Anderson study reported no excess of second malignancies among 350 patients with hairy cell leukemia who were treated with interferon alfa, cladribine, or pentostatin.[12]

 

Presentation

History

The most common symptoms and presenting complaints in hairy cell leukemia are weakness and fatigue due to anemia. Approximately one third of patients have bleeding from thrombocytopenia, and another third have fever and infections from neutropenia. 

Symptoms related to organ infiltration of the reticuloendothelial system may occur. Abdominal discomfort from an enlarged spleen is present in one quarter of patients. 

Some patients may present with weight loss, fever, and night sweats, similar to other lymphoproliferative disorders.

Hairy cell leukemia is associated with gram-positive and gram-negative bacterial infections, as well as atypical mycobacterial and invasive fungal infections. Other opportunistic infections, such as Legionella, toxoplasmosis, and listeriosis, have been reported.

Hairy cell leukemia is associated with other systemic immunologic disorders including the following:

  • Scleroderma
  • Polymyositis
  • Polyarteritis nodosa
  • Erythematous maculopapules
  • Pyoderma gangrenosum

Other uncommon conditions may be associated with hairy cell leukemia, such as acquired factor VIII antibodies, paraproteinemia, and systemic mast cell disease.

Physical Examination

Splenomegaly is the most common physical finding in hairy cell leukemia. It is present in virtually every patient with the disease and it is massive in more than 80% of patients. Hepatomegaly with mild liver function abnormalities is found in 20% of cases, and lymphadenopathy is found in 10%.

A low-grade fever is part of the disease, but it may alsobe due to an infection from the resulting neutropenia. In more than half of the cases, it is from a gram-negative organism. Atypical mycobacterial infections are common. Disseminated fungal infections and Pneumocystis jiroveci pneumonia may occur in some cases of hairy cell leukemia.

Peripheral lymphadenopathy is uncommon; fewer than 10% of patients present with peripheral nodes larger than 2 cm in diameter. However, internal adenopathy may develop after a prolonged disease course and was found in 75% of patients at autopsy.

 

DDx

Diagnostic Considerations

Hairy cell leukemia (HCL) must be differentiated from other other peripheral small B-cell lymphoid neoplasms, including hairy cell leukemia variant (HCL‐V), HCL expressing IGHV4-34, and splenic diffuse red pulp lymphoma (SDRPL). While those neoplasms are histologically similar to classic HCL, they have a more aggressive clinical course and are less likely to respond to purine analog therapy.[13]

Testing for BRAF-V600E allows for a genetics-based differential diagnosis between HCL and HCL-like tumors, as BRAF-V600E is absent in other B-cell neoplasms.[6, 14]

Other problems to be considered in the differential diagnosis of hairy cell leukemia include the following:

  • Primary myelofibrosis

  • Chronic lymphocytic leukemia

  • Low-grade lymphoma

  • Myelosclerosis

  • Pancytopenia and marrow fibrosis

  • Prolymphocytic leukemia

  • Splenic marginal zone lymphoma

  • Systemic mastocytosis

Differential Diagnoses

 

Workup

Approach Considerations

The diagnosis of hairy cell leukemia (HCL) is based on the following[13] :

  • Morphological evidence of hairy cells
  • An HCL immunologic score of 3 or 4 based on CD11C, CD103, CD123, and CD25 expression
  • Trephine bone marrow biopsy and/or aspiration, which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation 

International consensus guidelines recommend performing immunohistochemistry (IHC) or flow cytometry to establish a diagnosis of HCL and distinguish classic HCL from other histologically similar peripheral small B-cell lymphoid neoplasms. In addition to the BRAF V600E mutation, testing should include assays for CD19, CD20, CD5, CD10, CD11c, CD22, CD25, CD103, CD123, cyclin D1, and CD200.[15, 16, 17]

Laboratory Studies

Complete blood count and peripheral blood smear

A complete blood cell count (CBC) and careful review of a peripheral blood smear are the first steps in the identification of hairy cells. The typical hairy cells of hairy cell leukemia (HCL) are so named because of their characteristic cytoplasmic projections, which appear as fine (hairlike) microvilli when seen by light microscopy, phase-contrast microscopy, and electron microscopy. These are mononuclear cells with eccentric or centrally placed nuclei.

The CBC in patients with HCL typically shows pancytopenia, with decreased cell counts in all three cell lines, as follows:

  • Anemia is usually severe and normochromic-normocytic in character

  • Neutropenia and monocytopenia are usually present, but an elevated white blood cell count (hairy cells) is found in 20% of cases

  • Thrombocytopenia is found in more than 80% of patients

Trephine bone marrow biopsy and/or aspiration

The immunophenotypic profile of HCL is characterized by the clonal expansion of B‐cells with bright CD19, CD20, CD22, and CD200 expression. Hairy cells are usually negative or dim for CD5, CD23, CD10, CD79b, and CD27 but positive for CD11c, CD103, CD123, and CD25. A proposed immunological score gives one point to each of the last four markers when they are expressed. A score of 3 or 4 is observed in 98% of HCL cases, whereas in other HCL‐like disorders, the score is usually 0 or 1.[13]

The somatically acquired V600E mutation of the BRAF gene is present in nearly all patients with HCL and represents a reliable marker.[18]  BRAF- V600E can be reliably detected at the protein level by immunohistochemical stain using a mutant protein-specific antibody.[19]

A study by Tiacci et al examined the use of a test for genetically-based diagnosis of HCL. The molecular assay determines the presence of the BRAF-V600E mutation in order to differentiate between HCL and other disorders (eg, splenic marginal zone lymphoma, hairy cell leukemia variant). The study found that the molecular assay was a powerful tool for enhancing diagnostic accuracy.[20]

Genomic analysis of de novo vemurafenib-resistant classic HCL identified a novel gain-of-function mutation in IRS1 and losses of NF1 and NF2, each of which contributed to treatment resistance.[21]  

 

 

Imaging Studies

Most patients with hairy cell leukemia have massive splenomegaly, such that imaging studies are unnecessary to appreciate its presence. In milder forms, a liver and spleen scan or ultrasound measurement may detect mild organomegaly that could be missed by abdominal palpation.

Histologic Findings

The findings of pancytopenia and splenomegaly in the presence of circulating cells that are TRAP positive and a dry bone marrow aspirate with biopsy material showing infiltration with a mononuclear cells that have a fried-egg appearance are diagnostic of hairy cell leukemia.

 

Treatment

Approach Considerations

Patients with hairy cell leukemia (HCL) who have stable peripheral blood cell counts may be observed closely on a watch-and-wait program that entails at least quarterly blood cell counts and physical examinations.[22]  Approximately 10% of  patients, usually elderly men with moderate splenomegaly and mild decrease in blood counts, remain asymptomatic and never require therapy.

If the blood cell counts show a sustained decline or the patient becomes symptomatic (ie, develops fatigue or splenomegaly), then therapy with a purine analogue is started before the counts decline to dangerously low levels. Agents used are cladribine (2-chlorodeoxyadenosine [2-CdA]; Leustatin) and pentostatin (2-deoxyformycin [2'-DCF]; Nipent).

Blood cell counts may worsen temporarily after the initiation of either cladribine or pentostatin, so intervention should definitely begin before these hematologic parameters have deteriorated to levels requiring support. Because either of these agents is highly effective as monotherapy, most clinicians select the agent, dose, and schedule that they have effectively used in the past.

The data regarding the use of either pentostatin or cladribine alone for hairy cell leukemia suggest that these agents are equally effective in terms of response rate and remission duration.[9]  Furthermore, the long-term adverse effects are quite comparable. The concerns regarding increased risk for either late infections or secondary malignancies have not been fully resolved.

Substantial improvement in overall survival has been reported with initial use of either agent. Although close monitoring for late adverse effects of therapy is necessary, patients with hairy cell leukemia may now live as long as they would have without this diagnosis.[23] The progress in treatment changed the natural history of this disease. Although the best way to initiate therapy remains unsettled, there is a consensus that attaining a complete remission is important to reduce the possibility of a late relapse.

In selecting appropriate chemotherapy, the following clinical questions must be considered:

  • Is there evidence of active, untreated, ongoing infection?
  • Does the patient have a good performance status and adequate renal function?

Although it is prudent to attempt to treat an active infection before starting purine nucleoside analog therapy in a patient with hairy cell leukemia, the profound neutropenia and monocytopenia from the disease may force the decision to start antileukemic therapy. Otherwise, the patient may succumb to the infection. However, purine analogs may temporarily worsen the hematologic parameters. Most of the initial reports of cladribine indicate that this agent should not be administered to a patient with an ongoing infection.[24, 25]

The use of granulocyte colony-stimulating factor (G-CSF) can raise the absolute neutrophil count and shorten the period of severe neutropenia in hairy cell leukemia patients receiving cladribine, but routine use has not been shown to offer any clinical advantage.[26]

One strategy involves starting treatment with interferon alfa, to obtain an improvement in the granulocyte count that may enable the antibiotic or antifungal therapy to be more effective in controlling the infection; this is followed by a definitive purine analog therapy to achieve complete remission.[27]  Complete remission rates with interferon only are low, at 11% in patients without infection and 5% in patients with infection

Alternatively, pentostatin may be used. Although complete remission rates are better than with interferon—78% in uninfected patients  and 68% in infected patients—and the frequency of febrile episodes requiring antibiotic therapy is 27%, controlling infection if possible before starting pentostatin is recommended.

Pentostatin is cleared by the kidneys, so renal function must be carefully monitored during therapy. Patients with a serum creatinine of 1.5 mg/dL or higher should be excluded from receiving the drug. The initial dose is reduced to 2 mg/m2 in patients whose performance status is impaired, with subsequent escalation to full-dose therapy if tolerated. Hydration with 1.5 L of fluid is usually given along with each dose of the drug and the serum creatinine is checked before each subsequent infusion.

For more information, see Hairy Cell Leukemia Treatment Protocols.

Medical Care

The standard criteria for initiating therapy for hairy cell leukemia nclude the following:

  • Symptoms or blood transfusion requirement

  • Significant anemia with hemoglobin of 8-10 g/dL or less

  • Thrombocytopenia with platelet counts of 50,000-100,000/mL or less

  • Neutropenia with an absolute neutrophil count (ANC) of 500-1000/mL or less (see the Absolute Neutrophil Count calculator)

Less common indications for therapy include the following:

  • Leukocytosis with a high proportion of hairy cells

  • Repeated life-threatening infections

  • Symptomatic splenomegaly

  • Bulky or painful lymphadenopathy

  • Vasculitis

  • Bony involvement

The first-line therapy for hairy cell leukemia is cladribine, 0.1 mg/kg/d by continuous intravenous infusion for 7 days. The drug can be administered on an outpatient basis with a pump, after placement of a percutaneous intravenous central catheter (PICC).[28, 29, 30]

Growth factors are not routinely given but may be added in patients with febrile neutropenia. Platelet counts usually respond first (in 2-4 weeks), followed by white blood cell counts and neutrophil counts and, finally, hemoglobin levels. Bone marrow biopsy is repeated in 3 months, but minimal residual disease does not need therapy.

With one course of therapy of cladribine, 80% of patients obtain a complete remission (CR), and the remainder obtain a partial remission (PR). Several long-term studies have been reported. Chadha et al reported that although the overall survival rate at 12 years was 87%, the progression-free survival at 12 years was only 54%.[31] In addition, 17% of patients had developed another malignancy during that time.

For greater convenience, some groups have given cladribine as a 2-hour infusion (0.14 mg/kg/d) for 5 days. Zinzani et al reported a CR rate of 81% and a PR rate of 19% using this schedule.[4] The 13-year overall survival rate was 96%, and the relapse-free survival rate was 52%.[4] No randomized study comparing the 24-hour infusional versus the 2-hour infusional schedules is available.

In patients with minimal residual disease following treatment with cladribine, observation is currently the standard therapy. Ravandi et al reported that treatment with rituximab resulted in eradication of minimal residual disease in 11 of 12 patients with residual disease following cladribine therapy.[32]  Whether this treatment alters the natural history of hairy cell leukemia or prevents relapse is unclear.

For patients with relapsed hairy cell leukemia who have previously been treated with splenectomy, interferon, or pentostatin, retreatment with cladribine in the same manner is indicated, especially if their disease had previously responded to cladribine. In patients previously treated with cladribine, response rates of 50% are typical.[33]  In patients with relapsed or refractory hairy cell leukemia who are treated with rituximab, response rates of 50% are reported.

For patients with hairy cell leukemia that is refractory to cladribine, or if relapse occurs after two cycles of cladribine, the authors recommend treatment with pentostatin, 4 mg/m2 intravenously every 2 weeks for 3-6 months.[34]  Interferon alfa at 2 million U/m2 subcutaneously 3 times a week for 12-18 months can also be used to salvage relapsed or refractory hairy cell leukemia.

Another option for relapsed or refractory hairy cell leukemia is moxetumomab pasudotox (Lumoxiti), an anti-CD22 recombinant immunotoxin approved by the US Food and Drug Administration (FDA) in September 2018. Approval was based on efficacy and safety data from a single-arm, open-label phase III clinical trial in 80 patients. In this trial, the durable complete response (CR) rate was 30%, the CR rate was 41%, and the objective response rate (CR and partial response) was 75%. Also, 80% of patients achieved hematologic remission.[35]

Hyperuricemia may occur during therapy in patients with hairy cell leukemia who have leukocytosis and high tumor burden. Add allopurinol at 300 mg per day orally.

In patients who relapse within 2 years after monotherapy, it is important to differentiate classic hairy cell leukemia from the variant form. If classic hairy cell leukemia is confirmed, the patient should be considered for re-treatment with an alternative purine analogue or combination chemoimmunotherapy.[36]

Therapy with rituximab alone given in 4 or 8 weekly courses produces responses less impressive than combination therapy with a purine analogue, which is effective in patients who relapse after initial monotherapy. However, there are no randomized trials to conclusively prove that combination chemoimmunotherapy is more effective than monotherapy and that simultaneous purine analogue therapy is better than deliveriy of treatment in series.

Vemurafnib is a BRAF kinase inhibitor that is approved for use in other diseases that harbor a BRAF V600 mutation. In a multicenter study in Italy and the United States, treatment with vemurafenib (at a dose of 960 mg twice daily) proved effective in patients with relapsed or refractory disease after treatment with a purine analogue. Vemurafenib was given for a median of 16 weeks in the Italian arm and 18 weeks in the US arm. The overall response rates were 96% (25 of 26 patients) after a median of 8 weeks in the Italian cohort and 100% (24 of 24) after a median of 12 weeks in the US cohort. The rates of complete response were 35% (9 of 26 patients) and 42% (10 of 24) in Italy and the US, respectively.[37]

Surgical Care

Splenectomy was the first standard treatment modality for hairy cell leukemia and was used commonly in the past, but effective medical therapy has replaced splenectomy as the first-line treatment. Splenectomy is currently reserved for patients whose conditions fail to respond to systemic therapy or for those with bleeding from thrombocytopenia. Splenic size does not predict response to splenectomy. Patients undergoing splenectomy require appropriate vaccination.

Laparoscopic splenectomy has decreased the morbidity and duration of the postsurgical recovery period.

Although splenectomy does not produce pathologic remissions in the bone marrow, the peripheral blood cell counts improve in all three cell lines in approximately 40-70% of patients. This response occurs rapidly and usually lasts for a median of 20 months in approximately two thirds of patients, with an overall 5-year survival rate of 70%.

Long-Term Monitoring

Hairy cell leukemia is usually indolent and protracted; late relapses occur. Long-term outpatient follow-up is necessary in most patients.

Evaluation of minimal residual disease by posttreatment bone marrow biopsies using anti-CD20 by flow cytometry reveals that 13-51% of patients in apparent CR had minimal residual disease. The presence of minimal residual disease appears to predict clinical relapse. Because a majority of patients respond very well to retreatment (92% response) or salvage treatment (80% response), no evidence supports treatment of minimal residual disease.

Newer therapies, such as the anti-CD20 monoclonal antibody rituximab, have been tested in patients with hairy cell leukemia that was refractory to standard treatment. In studies with small numbers of patients who received rituximab, results ranged from an overall response of 64% with a median duration of response of 14 months, to 100% response with a duration of 73 months, indicating that this form of therapy is active against hairy cell leukemia.

 

Guidelines

Guidelines Summary

The following organizations have released guidelines for the management of hairy cell leukemia (HCL):

  • National Comprehensive Cancer Network (NCCN) [15]
  • European Society for Medical Oncology (ESMO)  [16]
  • Hairy Cell Leukemia Foundation (HCLF) [17]  

Diagnosis

According to NCCN guidelines, immunohistochemistry (IHC) and flow cytometry are essential for establishing a diagnosis of HCL and distinuguishing between HCL and hairy cell variant. The recommended tests include the following[15] :

  • Immunohistochemistry (IHC) panel or flow cytometry: CD19, CD20, CD5, CD10, CD11c, CD22, CD25, CD103, CD123, cyclin D1, and CD200
  • IHC for BRAF V600E mutation 

ESMO and HCLF recommendations concur with the above NCCN recommendations.[16, 17]  

Prognostic Factors

Although no international prognostic system for risk stratification of HCL has been developed, ESMO guidelines consider the following clinical variables to indicate an adverse prognosis[16] :

  • Severe cytopenias (hemoglobin [Hgb] < 10 g/dL, platelets < 100 × 10 9/L, neutrophils < 1 ×10 9/L )
  • Lymphadenopathy
  • Presence of TP53 mutations and lack of somatic mutations in the IGVH genes

In addition, the ESMO guidelines note that patients who achieve a complete response (CR) have a significantly longer disease-free survival than those who achieve a partial response.[16]

Treatment

NCCN guidelines recommend observation in the absence of the following clinical signs[15] :

  • Systematic symptoms
  • Splenic discomfort
  • Recurrent infection
  • Hgb < 12g/dL
  • Platelets < 100,000/μL
  • Absolute neutrophil count (ANC) < 1000/μL

If clinical indications are present, intial first-line treatments are the purine analogues cladribine or pentostatin.[15]

ESMO concurs with the NCCN recommendations, but includes an additional recommendation of interferon alfa for pregnant patients or those with very severe neutropenia.[16]

NCCN defines CR to treatment as the following[15] :

  • Near normalization of peripheral blood counts
  • Absence of HCL cells on bone marrow biopsy or peripheral blood samples
  • Regression of splenomegaly by physical exam
  • Hgb >11g/dL (without transfusion)
  • Platelets >100,000/μL
  • ANC >1500/μL

For patients who do not acheive CR or who relapse less than 24 months after achieving CR, NCCN recommends the following treatment options[15] :

  • Enrollment in appropriate clinical trial
  • Alternate purine analogue with or without rituximab
  • Rituximab monotherapy, if the patient is unable to receive purine analogues
  • Interferon alfa

For patients who relapse more than 24 months after achieving CR, NCCN recommends the following treatment options[15] :

  • Re-treat with the initial purine analogue with or without rituximab
  • Alternate purine analogue with or without rituximab
  • Rituximab monotherapy, if the patient is unable to receive purine analogues

For progressing disease thta is not responsive to purine analogue therapy, NCCN recommends enrollment in ca linical trial or vemurafenib with or without rituximab.[15]

Overall, ESMO guidelines are in agreement with NCCN, but include the following additional recommendations for treatment of refractory disease[16] :

  • Splenectomy may be indicated in patients with symptomatic splenomegaly (>10 cm below the costal margin) and low-level bone marrow infiltration
  • Allogeneic hematopoietic stem cell transplantation
  • Moxetumomab pasudotox
  • Fludarabine with rituximab
  • Bendamustine with rituximab
 

Medication

Medication Summary

Systemic therapy of hairy cell leukemia has changed rapidly in the past 10 years because of new biologic agents (eg, interferons) and new purine analogues. Also, the availability of recombinant human hematopoietic growth factors has improved supportive care during life-threatening infections in these patients.

Purine Analogues

Class Summary

Gibbett and coworkers observed that patients with severe combined immunodeficiency (SCID) were deficient in the purine catabolic enzyme adenosine deaminase. This deficiency causes intracellular accumulation of deoxyadenosine triphosphate and results in lymphocytotoxicity. Purine analogues mimic this condition by irreversibly binding to adenosine deaminase or by fostering resistance to deamination in the purine salvage pathway.

Cladribine or 2-chlorodeoxyadenosine (Leustatin)

Synthetic antineoplastic agent for continuous IV infusion. The enzyme deoxycytidine kinase phosphorylates this compound into active 5'-triphosphate derivative. This, in turn, breaks DNA strands, inhibits DNA synthesis, disrupts cell metabolism, and causes death to resting and dividing cells.

Most active among the purine analogues in the treatment of hairy cell leukemia. Has a 94% overall response and 84% complete response in hairy cell leukemia.

Patients whose disease does not respond to the initial regimen likely will not have a response to retreatment.

Pentostatin or 2-deoxycoformycin (Nipent)

Approved by the FDA for hairy cell leukemia but is less active than 2-CDA for this disease. Treatment results in a 79% overall response rate and a 64% complete response rate in patients with hairy cell leukemia. Response rates (CR + PR) of more than 90% have been reported.

Interferons

Class Summary

Interferons are naturally produced proteins with antitumor and immunomodulatory effects.

Interferon alfa 2a (Roferon)

Protein product manufactured by recombinant DNA technology. First systemic drug shown to partially eradicate hairy cells from bone marrow, and first approved indication was for this disease. The mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of the host immune response may play important roles.

Roferon and Intron A differ from the natural product only in amino acid residue at position 23 and achieve similar results in hairy cell leukemia. Response rates are 65% overall, with 10% of patients achieving a complete remission.

Interferon alfa-2b (Intron A)

Protein product manufactured by recombinant DNA technology. First systemic drug shown to partially eradicate hairy cells from bone marrow, and first approved indication was for this disease. The mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of the host immune response may play important roles.

Roferon and Intron A differ from the natural product only in amino acid residue at position 23 and achieve similar results in hairy cell leukemia. Response rates are 65% overall, with 10% of patients achieving a complete remission.

Recombinant Granulocyte Colony-Stimulating Factors (G-CSFs)

Class Summary

Because treatment of hairy cell leukemia is associated with neutropenia, use of G-CSF may be helpful in reducing the toxicity of treatment for hairy cell leukemia.

Filgrastim or G-CSF (Neupogen)

Shortens the early myelosuppressive effects of alfa interferon and reverses neutropenia in some patients with hairy cell leukemia.

Antineoplastics, Monoclonal Antibody

Class Summary

Moxetumomab pasudotox is the first monoclonal antibody (mAb) approved for hairy cell leukemia. After the mAb binds to CD22, the molecule is internalized; internalization results in ADP-ribosylation of elongation factor 2, inhibition of protein synthesis, and apoptotic cell death.

Moxetumomab pasudotox (Lumoxiti, moxetumomab pasudotox-tdfk)

Anti-CD22 recombinant immunotoxin. Indicated for adults with relapsed or refractory hairy cell leukemia (HCL) who have received at least 2 prior systemic therapies, including a purine nucleoside analog.

 

Questions & Answers

Overview

What is hairy cell leukemia (HCL)?

What is the pathophysiology of hairy cell leukemia (HCL)?

What is the prevalence of hairy cell leukemia (HCL)?

What is the prognosis of hairy cell leukemia (HCL)?

Presentation

Which clinical history findings are characteristic of hairy cell leukemia (HCL)?

Which systemic immunologic disorders are associated with hairy cell leukemia (HCL)?

Which physical findings are characteristic of hairy cell leukemia (HCL)?

DDX

How is hairy cell leukemia (HCL) differentiated from other peripheral small B-cell lymphoid neoplasms?

Which conditions are included in the differential diagnoses of hairy cell leukemia (HCL)?

What are the differential diagnoses for Hairy Cell Leukemia?

Workup

How is hairy cell leukemia (HCL) diagnosed?

What is the role of complete blood cell count (CBC) in the workup of hairy cell leukemia (HCL)?

What is the role of bone marrow aspiration in the diagnosis of hairy cell leukemia (HCL)?

What is the role of imaging studies in the workup of hairy cell leukemia (HCL)?

Which histologic findings are characteristic of hairy cell leukemia (HCL)?

Treatment

How is hairy cell leukemia (HCL) treated?

What are the indications for treatment of hairy cell leukemia (HCL)?

What is the role of cladribine in the treatment of hairy cell leukemia (HCL)?

How is refractory hairy cell leukemia (HCL) treated?

How is hairy cell leukemia (HCL) relapse treated?

What is the role of vemurafenib in the treatment of hairy cell leukemia (HCL)?

What is the role of surgery in the treatment of hairy cell leukemia (HCL)?

What is included in long-term monitoring of patients with hairy cell leukemia (HCL)?

Guidelines

Which organizations have released treatment guidelines for hairy cell leukemia (HCL)?

What are the NCCN diagnostic guidelines for hairy cell leukemia (HCL)?

What does the ESMO guidelines consider prognostic indicators for hairy cell leukemia (HCL)?

What are the NCCN guidelines for hairy cell leukemia (HCL) treatment?

What are the ESMO guidelines for hairy cell leukemia (HCL) treatment?

Medications

Which medications are used in the treatment of hairy cell leukemia (HCL)?

Which medications in the drug class Antineoplastics, Monoclonal Antibody are used in the treatment of Hairy Cell Leukemia?

Which medications in the drug class Recombinant Granulocyte Colony-Stimulating Factors (G-CSFs) are used in the treatment of Hairy Cell Leukemia?

Which medications in the drug class Interferons are used in the treatment of Hairy Cell Leukemia?

Which medications in the drug class Purine Analogues are used in the treatment of Hairy Cell Leukemia?