eMedicine Specialties > Hematology > Stem Cells and Disorders

Hairy Cell Leukemia: Treatment & Medication

Author: Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Coauthor(s): Ulrich Woermann, MD, Consulting Staff, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland
Contributor Information and Disclosures

Updated: Nov 24, 2008

Treatment

Medical Care

Chemotherapeutic approaches

The first-line therapy for hairy cell leukemia is 2-chlorodeoxyadenosine (2-CdA) 0.1 mg/kg/d (Cladribine, Leustatin) by continuous intravenous infusion for 7 days, which can be performed on an outpatient basis with a pump, using a percutaneous intravenous central catheter (PICC).^5,6 Growth factors are not routinely given but may be added in patients with febrile neutropenia. The response is usually first observed in the platelet counts (in 2-4 wk) followed by white blood cell counts and neutrophils 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 2-CdA, 80% of patients obtain a complete remission (CR), and the remainder obtains 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%.⁷ In addition, 17% of patients had developed another malignancy during that time.

For increased convenience, some groups have given 2-CdA 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.⁸ The 13-year overall survival rate was 96%, and the relapse-free survival rate was 52%.⁸ No randomized study comparing the 24-hour infusional versus the 2-hour infusional schedules is available.

A current trend is the significance of minimal residual disease following treatment with 2-CdA. Ravandi et al administered rituximab to patients with residual disease following 2-CdA.⁹ Eleven of 12 patients had eradication of minimal residual disease with this treatment. Whether this will alter the natural history of hairy cell leukemia or prevent relapse is unclear. Currently, the standard therapy for patients with minimal residual disease is observation.

For patients with relapsed hairy cell leukemia who have previously been treated with splenectomy, interferon, or 2-deoxyformycin (2'-DCF, Pentostatin), retreatment with 2-CdA in the same manner is indicated, especially if their disease had previously responded to 2-CdA. In patients previously treated with 2-CdA, response rates of 50% are typical.

Rituximab is a monoclonal antibody against CD20. In patients with relapsed or refractory hairy cell leukemia, response rates of 50% are reported.

• Hairy cell leukemia may behave as a chronic leukemia without causing any symptoms. Approximately 10% of cases, usually in elderly men with moderate splenomegaly and mild decrease in blood counts, never require therapy.
• The standard criteria for initiating therapy include 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
• 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
• For patients with hairy cell leukemia that is refractory to 2-CdA, or if relapse occurs after 2 cycles of 2-CdA, the authors recommend treatment with 2'-deoxycoformycin (2'DCF, Pentostatin) 4 mg/m² intravenously every 2 weeks for 3-6 months.¹⁰
• Alpha interferon at 2 million U/m² subcutaneously 3 times a week for 12-18 months can be used to salvage relapsed or refractory hairy cell leukemia.

Surgical Care

• Splenectomy was the first standard treatment modality and was used commonly in the past, but this propcedure has been replaced by the newer agents available. Cytopenia improved rapidly in most patients. Although splenectomy does not produce pathologic remissions in the bone marrow, the peripheral blood cell counts improve in all 3 cell lines in approximately 40-70% of patients. This response usually lasts for a median of 20 months in approximately two thirds of patients, with an overall survival rate of 70% in 5 years.
• Splenic size does not predict response to splenectomy.
• Effective medical therapy has replaced splenectomy as the first-line treatment for hairy cell leukemia.
• Splenectomy is currently reserved for patients whose conditions fail to respond to systemic therapy or for those with bleeding from thrombocytopenia. Patients undergoing splenectomy require appropriate vaccination.
• Laparoscopic splenectomy has decreased the morbidity and duration of the postsurgical recovery period.

Medication

Systemic therapy 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 those with hairy cell leukemia.

Purine Analogues

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

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)

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.

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