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.
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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.
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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.
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Blood film at × 1000 magnification. This image demonstrates tartrate-resistant acid phosphatase (TRAP) activity of lymphocytes. Photographed by U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
