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PDQ®
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Hairy cell leukemia is a chronic lymphoproliferative disorder that is easily controlled. Decision to treat is based on symptomatic cytopenias, massive splenomegaly, or the presence of other complications. About one-tenth of all patients will never require therapy.
There is no generally accepted staging system that is useful both for prognosis and therapy.
For the purpose of treatment decisions, it is best to consider this disease in two broad categories: untreated hairy cell leukemia and progressive hairy cell leukemia, either post-splenectomy or post-systemic 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 ("hairy cells"). The bone marrow is usually fibrotic and is not easily aspirated. Bone marrow biopsies are therefore required for diagnosis and evaluation of the degree of hairy cell infiltration.
Progressive hairy cell leukemia, post-splenectomy (or following any systemic therapy) is characterized by progressive bone marrow replacement by hairy cells, with pancytopenia refractory to treatment. For patients with advanced hairy cell leukemia treated with 2-chlorodeoxyadenosine (2-CdA), pentostatin, or interferon alfa, the survival rate appears to be greater than 85% at 5 years after the initiation of any one of these therapies.[1,2]
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The initial therapies of choice are either 2-chlorodeoxyadenosine (2-CdA) or pentostatin. These drugs have comparable response rates but have not been compared in phase III trials. 2-CdA is administered as a one-time continuous infusion or series of subcutaneous injections, and is associated with a high rate of febrile neutropenia.[1-3] Rarely, more than 1 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.[4] The role of consolidation or maintenance therapy in preventing relapse or progression of the disease following treatment with purine analogs has not been evaluated and remains unproven. Pentostatin is administered intermittently for a longer treatment duration but may result in a lower incidence of febrile complications.[5,6] While some patients remain disease-free 6 years after treatment with these purine analogues, no patient has been followed long enough to assess cure. Both nucleoside analogues cause profound suppression of CD4 counts which may last for a year. With prolonged survival associated with prolonged treatment with purine analogues, there is an increased risk of second malignancies among patients with hairy cell leukemia (observed to expected ratio of about 1.8 in several series after 6 years).[3,7] For a few patients, such as those with severe thrombocytopenia, splenectomy can be considered.[8] After splenectomy, one-half of patients will require no additional therapy and long-term survivors are common. Therapy with interferon alfa is another treatment option, especially for patients with intercurrent infection.[6,9]
The designations in PDQ that treatments are "standard" or "under clinical evaluation" are not to be used as a basis for reimbursement determinations.
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Hairy cell leukemia is a highly treatable disease. Since 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 blood counts are maintained in an acceptable range.[1]
Treatment options:
2. 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.[9,10] Complete remissions are of substantial duration. Side effects include fever, immunosuppression, cytopenias, and renal dysfunction. A randomized comparison of pentostatin and interferon alfa demonstrated higher and more durable responses to pentostatin.[9]
3. 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 respond to retreatment with interferon alfa.[11] Remission can be prolonged with a low-dose maintenance regimen.[12] A randomized comparison of pentostatin and interferon alfa demonstrated significantly higher and more durable responses to pentostatin.[9]
4. Splenectomy will partially or completely normalize the peripheral blood in the vast majority of patients with hairy cell leukemia.[13] There is usually little or no change in the bone marrow after splenectomy, and virtually all patients have progressive disease within 12 to 18 months. Therefore, since a number of more effective alternatives are available, splenectomy is playing a decreasing role in the treatment of this disease.
2-Chlorodeoxyadenosine (2-CdA) and pentostatin are both highly efficacious in the treatment of patients with disease refractory to interferon alfa.[1-4] Evidence suggests that fludarabine may also be active in patients who are refractory to interferon alfa or pentostatin.[5] Relapsing patients often respond to retreatment with 2-CdA.[6-8]
Allogeneic bone marrow transplantation may be considered for selected patients in rare instances. The patients should be in good health and have an HLA-identical sibling. The high mortality of this procedure justifies its use only in refractory cases.[9]
Aggressive, high-dose chemotherapy has been beneficial in some cases, but the associated morbidity and mortality are high. It should not be considered unless other more frequently effective therapies have been exhausted.
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Date Last Modified: 11/1999
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Treatment