Hairy Cell Leukemia

Summary Type: Treatment
Summary Audience: Health professionals
Summary Language: English
Summary Description: Expert-reviewed information summary about the treatment of hairy cell leukemia.

Hairy Cell Leukemia

General Information

Hairy cell leukemia is a chronic lymphoproliferative disorder that is easily controlled. 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.

Stage Information

No generally accepted staging system is useful for both prognosis and therapy.

For the purpose of treatment decisions, it is best to consider this disease in 2 broad categories: untreated hairy cell leukemia and progressive hairy cell leukemia, either postsplenectomy or postsystemic therapy.

Untreated hairy cell leukemia

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. Bone marrow biopsies are, therefore, required for diagnosis and evaluation of the degree of hairy cell infiltration.

Progressive hairy cell leukemia

Progressive hairy cell leukemia, postsplenectomy (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 cladribine (2-chlorodeoxyadenosine, 2-CdA), pentostatin, or interferon alfa, the survival rate appears to be >85% at 5 years after the initiation of any one of these therapies.^1,2

¹ Frassoldati A, Lamparelli T, Federico M, et al.: Hairy cell leukemia: a clinical review based on 725 cases of the Italian Cooperative Group (ICGHCL). Italian Cooperative Group for Hairy Cell Leukemia. Leuk Lymphoma 13 (3-4): 307-16, 1994.

² Kurzrock R, Strom SS, Estey E, et al.: Second cancer risk in hairy cell leukemia: analysis of 350 patients. J Clin Oncol 15 (5): 1803-10, 1997.

Treatment Option Overview

The initial therapies of choice are either cladribine (2-chlorodeoxyadenosine, 2-CdA) or pentostatin.¹ 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.^2,3,4,5 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.^4,6,

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.^7,8 While most patients remain disease-free 10 years after treatment with these purine analogs, no patient has been followed long enough to assess cure.^9,10 Both nucleoside analogs cause profound suppression of CD4 counts, which may last for a year. 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).^4,11 Several series using pentostatin did not report an increased risk of second malignancies.^7,9,12 For a few patients, such as those with severe thrombocytopenia, splenectomy can be considered.¹³ After splenectomy, 50% 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.^8,14,

The designations in PDQ that treatments are “standard” or “under clinical evaluation” are not to be used as a basis for reimbursement determinations.

¹ Tallman MS, Peterson LC, Hakimian D, et al.: Treatment of hairy-cell leukemia: current views. Semin Hematol 36 (2): 155-63, 1999.

² Hoffman MA, Janson D, Rose E, et al.: Treatment of hairy-cell leukemia with cladribine: response, toxicity, and long-term follow-up. J Clin Oncol 15 (3): 1138-42, 1997.

³ Cheson BD, Sorensen JM, Vena DA, et al.: Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine via the Group C protocol mechanism of the National Cancer Institute: a report of 979 patients. J Clin Oncol 16 (9): 3007-15, 1998.

⁴ Goodman GR, Burian C, Koziol JA, et al.: Extended follow-up of patients with hairy cell leukemia after treatment with cladribine. J Clin Oncol 21 (5): 891-6, 2003.

⁵ Jehn U, Bartl R, Dietzfelbinger H, et al.: An update: 12-year follow-up of patients with hairy cell leukemia following treatment with 2-chlorodeoxyadenosine. Leukemia 18 (9): 1476-81, 2004.

⁶ Fayad L, Kurzrock R, Keating M, et al.: Treatment of hairy-cell leukemia (HCL) with 2-CdA: long term follow-up at M.D. Anderson Cancer Center. Blood 90(suppl 1): A2363, 1997.

⁷ Ribeiro P, Bouaffia F, Peaud PY, et al.: Long term outcome of patients with hairy cell leukemia treated with pentostatin. Cancer 85 (1): 65-71, 1999.

⁸ Grever M, Kopecky K, Foucar MK, et al.: Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study. J Clin Oncol 13 (4): 974-82, 1995.

⁹ Flinn IW, Kopecky KJ, Foucar MK, et al.: Long-term follow-up of remission duration, mortality, and second malignancies in hairy cell leukemia patients treated with pentostatin. Blood 96 (9): 2981-6, 2000.

¹⁰ Chadha P, Rademaker AW, Mendiratta P, et al.: Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA): long-term follow-up of the Northwestern University experience. Blood 106 (1): 241-6, 2005.

¹¹ Au WY, Klasa RJ, Gallagher R, et al.: Second malignancies in patients with hairy cell leukemia in british columbia: a 20-year experience. Blood 92 (4): 1160-4, 1998.

¹² Kurzrock R, Strom SS, Estey E, et al.: Second cancer risk in hairy cell leukemia: analysis of 350 patients. J Clin Oncol 15 (5): 1803-10, 1997.

¹³ Golomb HM, Vardiman JW: Response to splenectomy in 65 patients with hairy cell leukemia: an evaluation of spleen weight and bone marrow involvement. Blood 61 (2): 349-52, 1983.

¹⁴ Capnist G, Federico M, Chisesi T, et al.: Long term results of interferon treatment in hairy cell leukemia. Italian Cooperative Group of Hairy Cell Leukemia (ICGHCL). Leuk Lymphoma 14 (5-6): 457-64, 1994.

Untreated Hairy Cell Leukemia

Initial treatment

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,

Progressive hairy cell leukemia

Standard treatment options:

1. Cladribine (2-chlorodeoxyadenosine, 2-CdA) given intravenously by continuous infusion or as daily subcutaneous injections for 1 week results in a complete response rate of 50% to 80% and an overall response rate of 85% to 95%.^{1,2,3,4,5,6,7,8} 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).⁵ Responses are durable with this short course of therapy, and patients who relapse often respond to retreatment with cladribine.^9,10 This drug may cause fever and immunosuppression with documented infection in 33% of treated patients.⁵ In a retrospective study of patients with cladribine-associated neutropenic fever, filgrastim (G-CSF) did not demonstrate a decrease in the percentage of febrile patients, number of febrile days, or frequency of admissions for antibiotics.¹¹ A potential increased risk for second malignancies with this agent remains controversial.
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.^12,13 Complete remissions are of substantial duration. In 2 trials with 9-year median follow-up, relapse-free survival ranged from 56% to 67%.^14,15 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.^12,
3. Interferon alfa 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 respond to retreatment with interferon alfa.¹⁶ Remission can be prolonged with a low-dose maintenance regimen.¹⁷ A randomized comparison of pentostatin and interferon alfa demonstrated significantly higher and more durable responses to pentostatin.^12,
4. Splenectomy will partially or completely normalize the peripheral blood in the vast majority of patients with hairy cell leukemia.¹⁸ 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, since a number of more effective alternatives are available, splenectomy is playing a decreasing role in the treatment of this disease.

¹ Saven A, Piro L: Newer purine analogues for the treatment of hairy-cell leukemia. N Engl J Med 330 (10): 691-7, 1994.

² Juliusson G, Heldal D, Hippe E, et al.: Subcutaneous injections of 2-chlorodeoxyadenosine for symptomatic hairy cell leukemia. J Clin Oncol 13 (4): 989-95, 1995.

³ Tallman MS, Hakimian D, Variakojis D, et al.: A single cycle of 2-chlorodeoxyadenosine results in complete remission in the majority of patients with hairy cell leukemia. Blood 80 (9): 2203-9, 1992.

⁴ Hoffman MA, Janson D, Rose E, et al.: Treatment of hairy-cell leukemia with cladribine: response, toxicity, and long-term follow-up. J Clin Oncol 15 (3): 1138-42, 1997.

⁵ Cheson BD, Sorensen JM, Vena DA, et al.: Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine via the Group C protocol mechanism of the National Cancer Institute: a report of 979 patients. J Clin Oncol 16 (9): 3007-15, 1998.

⁶ Goodman GR, Burian C, Koziol JA, et al.: Extended follow-up of patients with hairy cell leukemia after treatment with cladribine. J Clin Oncol 21 (5): 891-6, 2003.

⁷ Lauria F, Bocchia M, Marotta G, et al.: Weekly administration of 2-chlorodeoxyadenosine in patients with hairy-cell leukemia: a new treatment schedule effective and safer in preventing infectious complications. Blood 89 (5): 1838-9, 1997.

⁸ Robak T, Błasińska-Morawiec M, Krykowski E, et al.: 2-chlorodeoxyadenosine (2-CdA) in 2-hour versus 24-hour intravenous infusion in the treatment of patients with hairy cell leukemia. Leuk Lymphoma 22 (1-2): 107-11, 1996.

⁹ Jehn U, Bartl R, Dietzfelbinger H, et al.: An update: 12-year follow-up of patients with hairy cell leukemia following treatment with 2-chlorodeoxyadenosine. Leukemia 18 (9): 1476-81, 2004.

¹⁰ Chadha P, Rademaker AW, Mendiratta P, et al.: Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA): long-term follow-up of the Northwestern University experience. Blood 106 (1): 241-6, 2005.

¹¹ Saven A, Burian C, Adusumalli J, et al.: Filgrastim for cladribine-induced neutropenic fever in patients with hairy cell leukemia. Blood 93 (8): 2471-7, 1999.

¹² Grever M, Kopecky K, Foucar MK, et al.: Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study. J Clin Oncol 13 (4): 974-82, 1995.

¹³ Ribeiro P, Bouaffia F, Peaud PY, et al.: Long term outcome of patients with hairy cell leukemia treated with pentostatin. Cancer 85 (1): 65-71, 1999.

¹⁴ Johnston JB, Eisenhauer E, Wainman N, et al.: Long-term outcome following treatment of hairy cell leukemia with pentostatin (Nipent): a National Cancer Institute of Canada study. Semin Oncol 27 (2 Suppl 5): 32-6, 2000.

¹⁵ Flinn IW, Kopecky KJ, Foucar MK, et al.: Long-term follow-up of remission duration, mortality, and second malignancies in hairy cell leukemia patients treated with pentostatin. Blood 96 (9): 2981-6, 2000.

¹⁶ Golomb HM, Ratain MJ, Fefer A, et al.: Randomized study of the duration of treatment with interferon alfa-2B in patients with hairy cell leukemia. J Natl Cancer Inst 80 (5): 369-73, 1988.

¹⁷ Capnist G, Federico M, Chisesi T, et al.: Long term results of interferon treatment in hairy cell leukemia. Italian Cooperative Group of Hairy Cell Leukemia (ICGHCL). Leuk Lymphoma 14 (5-6): 457-64, 1994.

¹⁸ Golomb HM, Vardiman JW: Response to splenectomy in 65 patients with hairy cell leukemia: an evaluation of spleen weight and bone marrow involvement. Blood 61 (2): 349-52, 1983.

Relapsed or Refractory Hairy Cell Leukemia

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Cladribine (2-chlorodeoxyadenosine, 2-CdA) and pentostatin are both highly efficacious in the treatment of patients with disease refractory to interferon alfa.^1,2,3,4 Rituximab can induce durable complete remissions with minimal toxic effects in the majority of patients with relapsing or refractory disease after purine analog therapy.^5,6,7,[Level of evidence: 3iiiDiii] The lack of subsequent immunosuppression with rituximab has made this treatment the first choice among relapsing patients in the absence of a clinical trial.⁷ Patients who relapse after cladribine or pentostatin often respond to retreatment with the same or another purine analog.^8,9,10,11 An anti-CD22 recombinant immunotoxin under clinical evaluation can induce complete remissions in patients resistant to retreatment with purine analogs.^12,[Level of evidence: 3iiiDiii]

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.^13,

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.

¹ Blick M, Lepe-Zuniga JL, Doig R, et al.: Durable complete remissions after 2'-deoxycoformycin treatment in patients with hairy cell leukemia resistant to interferon alpha. Am J Hematol 33 (3): 205-9, 1990.

² Piro LD, Carrera CJ, Carson DA, et al.: Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine. N Engl J Med 322 (16): 1117-21, 1990.

³ Estey EH, Kurzrock R, Kantarjian HM, et al.: Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA). Blood 79 (4): 882-7, 1992.

⁴ Tallman MS, Hakimian D, Variakojis D, et al.: A single cycle of 2-chlorodeoxyadenosine results in complete remission in the majority of patients with hairy cell leukemia. Blood 80 (9): 2203-9, 1992.

⁵ Hagberg H, Lundholm L: Rituximab, a chimaeric anti-CD20 monoclonal antibody, in the treatment of hairy cell leukaemia. Br J Haematol 115 (3): 609-11, 2001.

⁶ Lauria F, Lenoci M, Annino L, et al.: Efficacy of anti-CD20 monoclonal antibodies (Mabthera) in patients with progressed hairy cell leukemia. Haematologica 86 (10): 1046-50, 2001.

⁷ Thomas DA, O'Brien S, Bueso-Ramos C, et al.: Rituximab in relapsed or refractory hairy cell leukemia. Blood 102 (12): 3906-11, 2003.

⁸ Hoffman MA, Janson D, Rose E, et al.: Treatment of hairy-cell leukemia with cladribine: response, toxicity, and long-term follow-up. J Clin Oncol 15 (3): 1138-42, 1997.

⁹ Goodman GR, Burian C, Koziol JA, et al.: Extended follow-up of patients with hairy cell leukemia after treatment with cladribine. J Clin Oncol 21 (5): 891-6, 2003.

¹⁰ Ribeiro P, Bouaffia F, Peaud PY, et al.: Long term outcome of patients with hairy cell leukemia treated with pentostatin. Cancer 85 (1): 65-71, 1999.

¹¹ Zinzani PL, Magagnoli M, Bendandi M, et al.: Long-term follow-up of hairy cell leukemia patients treated with 2-chlorodeoxyadenosine. Haematologica 85 (9): 922-5, 2000.

¹² Kreitman RJ, Wilson WH, Bergeron K, et al.: Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia. N Engl J Med 345 (4): 241-7, 2001.

¹³ Cheever MA, Fefer A, Greenberg PD, et al.: Treatment of hairy-cell leukemia with chemoradiotherapy and identical-twin bone-marrow transplantation. N Engl J Med 307 (8): 479-81, 1982.

Changes to This Summary (11/21/2005)

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 Option Overview

Added Chadha et al. as reference 10.

Untreated Hairy Cell Leukemia

Added Chadha et al. as reference 10.

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