Hairy Cell Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI]

General Information About Hairy Cell Leukemia

Prognostic Factors

Hairy cell leukemia is an indolent, low-grade, B-cell lymphoma usually characterized by the following:

• Circulating B-cells with cytoplasmic projections ("hairy" appearance).
• Splenomegaly.
• Absent lymphadenopathy.
• Pancytopenia.
• Monocytopenia.

Diagnosis

In addition to the B-cell antigens CD19, CD20, and CD22, the cells coexpress CD11c, CD25, and CD103. The BRAF-V600E mutation is a hairy cell leukemia–defining genetic lesion that can be used diagnostically.[1,2] 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.

References:

1. Tiacci E, Schiavoni G, Forconi F, et al.: Simple genetic diagnosis of hairy cell leukemia by sensitive detection of the BRAF-V600E mutation. Blood 119 (1): 192-5, 2012.
2. Naik RR, Saven A: My treatment approach to hairy cell leukemia. Mayo Clin Proc 87 (1): 67-76, 2012.

Stage Information for Hairy Cell Leukemia

No generally accepted staging system is useful for both prognosis and 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 (i.e., hairy cells). The bone marrow is usually fibrotic and is not easily aspirated; therefore, bone marrow biopsies are required for diagnosis and evaluation of the degree of hairy cell infiltration.

After the initiation of treatment with cladribine (2-chlorodeoxyadenosine, 2-CdA), pentostatin, or interferon-alpha, the survival rate of patients with advanced hairy cell leukemia appears to be higher than 85% at 5 years' follow-up.[1]

References:

1. Grever MR, Abdel-Wahab O, Andritsos LA, et al.: Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia. Blood 129 (5): 553-560, 2017.

Treatment Option Overview for Hairy Cell Leukemia

The initial therapies of choice for hairy cell leukemia are either cladribine (2-chlorodeoxyadenosine, 2-CdA) or pentostatin.[1,2] 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.[3,4,5,6] 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.[5,7]

The role of consolidation or maintenance therapy in preventing relapse or progression of the disease after treatment with purine analogs has not been evaluated and remains unproven. Pentostatin is administered intermittently for a longer time but may result in a lower incidence of febrile complications.[8,9] While most patients remain disease free 10 years after treatment with these purine analogs, no patient has been monitored long enough to assess cure.[10,11] Both nucleoside analogs cause profound suppression of CD4 counts, which may last for a year, and a potential increased risk of second malignancies has been reported.[5,12]

A study of 3,104 survivors of hairy cell leukemia from the Surveillance, Epidemiology, and End Results (SEER) database showed an increased risk of second cancers (standardized incidence ratio, 1.24; 95% confidence interval, 1.11–1.37), especially for Hodgkin and non-Hodgkin lymphomas.[13] The increased risk for second cancers was seen even in the two decades before the introduction of purine nucleosides.[13] 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).[5,12] Several series using pentostatin did not report an increased risk of second malignancies.[8,10,14] For a few patients, such as those with severe thrombocytopenia, splenectomy might be considered.[15] After splenectomy, 50% of patients will require no additional therapy, and long-term survivors are common. Therapy with interferon-alpha is another treatment option, especially for patients with intercurrent infection.[9,16]

The hairy cell leukemia variant has a distinctive phenotype and typically presents with leukocytosis instead of leukopenia.[17,18] Patients with this variant have poorer responses to initial cladribine, have shorter durations of response, and typically do not respond again to purine analogs after relapse. Combinations of rituximab and purine analogs are under evaluation, and further studies are required to define optimal therapies.[19]

References:

1. Gidron A, Tallman MS: 2-CdA in the treatment of hairy cell leukemia: a review of long-term follow-up. Leuk Lymphoma 47 (11): 2301-7, 2006.
2. Grever MR, Lozanski G: Modern strategies for hairy cell leukemia. J Clin Oncol 29 (5): 583-90, 2011.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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. [Abstract] Blood 90 (suppl 1): A-2363, 1997.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. Hisada M, Chen BE, Jaffe ES, et al.: Second cancer incidence and cause-specific mortality among 3104 patients with hairy cell leukemia: a population-based study. J Natl Cancer Inst 99 (3): 215-22, 2007.
14. 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.
15. 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.
16. 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.
17. Matutes E, Wotherspoon A, Catovsky D: The variant form of hairy-cell leukaemia. Best Pract Res Clin Haematol 16 (1): 41-56, 2003.
18. Arons E, Suntum T, Stetler-Stevenson M, et al.: VH4-34+ hairy cell leukemia, a new variant with poor prognosis despite standard therapy. Blood 114 (21): 4687-95, 2009.
19. Else M, Osuji N, Forconi F, et al.: The role of rituximab in combination with pentostatin or cladribine for the treatment of recurrent/refractory hairy cell leukemia. Cancer 110 (10): 2240-7, 2007.

Treatment for Hairy Cell Leukemia

Hairy cell leukemia is a highly treatable disease. Because 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 if blood counts are maintained in an acceptable range.

Standard Treatment Options for Hairy Cell Leukemia

Standard treatment options for hairy cell leukemia include the following:

1. Cladribine with or without rituximab.
2. Pentostatin.
3. Interferon-alpha.
4. Splenectomy.

Cladribine with or without rituximab

Cladribine (2-chlorodeoxyadenosine, 2-CdA) given intravenously by daily subcutaneous injections, or by 2-hour infusions daily for 5 to 7 days results in a complete response rate of 50% to 80% and an overall response rate of 85% to 95%.[1,2,3][Level of evidence: 3iiiDiv] 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). Responses are durable with this short course of therapy, and patients who relapse often respond to re-treatment with cladribine.[4,5,6]

Evidence (cladribine with or without rituximab):

1. A retrospective review included 83 patients, aged 40 years and younger.[7]
   • The median time to first relapse was 54 months for all responders and the median overall survival was 21 years from diagnosis.
   • This drug may cause fever and immunosuppression; documented infection was found in 33% of treated patients.
2. 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.[8] There is a potential increased risk of developing second malignancies with this agent.
3. In a randomized phase II study, 68 patients with previously untreated hairy cell leukemia were randomly assigned to receive cladribine 0.15 mg/kg intravenously on days 1 to 5 with 8 weekly doses of rituximab concurrently (starting on day 1) or after 6 months if still positive with minimal residual disease (MRD) testing.[9]
   • With a median follow-up of 96 months, 94% of patients who received concurrent therapy were MRD-free, compared with 12% of patients who received delayed therapy.[9][Level of evidence: 3iiiDiv]
   • Concurrent therapy resulted in more need for platelet transfusions, but also higher neutrophil and platelet counts after one month.

MRD testing in this setting has never been validated as a clinically significant endpoint. This concept requires further study, but hairy cell leukemia is rare, with 600 to 800 new cases annually in the United States.

Pentostatin

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.[10,11] Complete remissions are of substantial duration.

Evidence (pentostatin):

1. In two trials with 9-year median follow-ups, relapse-free survival ranged from 56% to 67%.[12,13]
   • Side effects included fever, immunosuppression, cytopenias, and renal dysfunction.
2. A randomized comparison of pentostatin and interferon-alpha demonstrated higher and more durable responses to pentostatin.[10]

Interferon-alpha

Interferon-alpha 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 react positively to re-treatment with interferon-alpha.[14] Remission can be prolonged with a low-dose maintenance regimen.[15]

Evidence (interferon-alpha):

1. A randomized comparison of pentostatin and interferon-alpha demonstrated significantly higher and more durable responses to pentostatin.[10]

Splenectomy

Splenectomy will partially or completely normalize the peripheral blood in the vast majority of patients with hairy cell leukemia.[16] 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, because a number of more effective alternatives are available, splenectomy is playing a decreasing role in the treatment of this disease.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

1. 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.
2. Robak T, Jamroziak K, Gora-Tybor J, et al.: Cladribine in a weekly versus daily schedule for untreated active hairy cell leukemia: final report from the Polish Adult Leukemia Group (PALG) of a prospective, randomized, multicenter trial. Blood 109 (9): 3672-5, 2007.
3. Zenhäusern R, Schmitz SF, Solenthaler M, et al.: Randomized trial of daily versus weekly administration of 2-chlorodeoxyadenosine in patients with hairy cell leukemia: a multicenter phase III trial (SAKK 32/98). Leuk Lymphoma 50 (9): 1501-11, 2009.
4. 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.
5. 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.
6. Else M, Dearden CE, Matutes E, et al.: Long-term follow-up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosis. Br J Haematol 145 (6): 733-40, 2009.
7. Rosenberg JD, Burian C, Waalen J, et al.: Clinical characteristics and long-term outcome of young hairy cell leukemia patients treated with cladribine: a single-institution series. Blood 123 (2): 177-83, 2014.
8. 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.
9. Chihara D, Arons E, Stetler-Stevenson M, et al.: Randomized Phase II Study of First-Line Cladribine With Concurrent or Delayed Rituximab in Patients With Hairy Cell Leukemia. J Clin Oncol 38 (14): 1527-1538, 2020.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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

Treatment Options for Relapsed or Refractory Hairy Cell Leukemia

Treatment options for relapsed or refractory hairy cell leukemia include the following:

1. Re-treatment with cladribine or pentostatin.
2. Rituximab.
3. Purine analog plus rituximab.
4. Vemurafenib with or without rituximab.
5. Moxetumomab pasudotox-tdfk.
6. Ibrutinib.
7. Interferon-alpha.
8. Splenectomy.

Re-treatment with cladribine or pentostatin

Patients with hairy cell leukemia who relapse after the first course of cladribine or pentostatin often respond well to re-treatment with the same or another purine analog, especially if relapse occurs after 2 years.[1,2,3,4,5,6][Level of evidence: 3iiiDiv]

Rituximab

Rituximab can induce durable complete remissions with minimal toxic effects in patients with multiple relapsing or refractory disease after purine analog therapy or after treatment with interferon.[7,8,9,10,11][Level of evidence: 3iiiDiv]

Purine analog plus rituximab

Combinations or the sequential use of rituximab with either cladribine or pentostatin are effective in achieving complete remission and are under clinical evaluation.[12,13,14,15][Level of evidence: 3iiiDiv]

Vemurafenib with or without rituximab

The BRAF-V600E mutation occurs in almost 100% of classic-form hairy cell leukemia patients and almost never in other B-cell lymphomas and leukemias, including hairy cell leukemia variants.[16][Level of evidence: 3iiiDiv] Vemurafenib can be given in combination with rituximab.

Evidence (vemurafenib with or without rituximab):

1. Two phase II, multicenter studies in the United States and Italy evaluated the BRAF inhibitor vemurafenib, given orally for 4 months.[17,18]
   • After a median follow-up of 23 months, the overall response rate for 50 patients was 98%, the complete response rate was 38%, and the median treatment-free survival was 25 months and 18 months in the two studies.[17,18][Level of Evidence: 3iiiDiv]

Moxetumomab pasudotox-tdfk

Moxetumomab pasudotox-tdfk is an anti-CD22 recombinant immunotoxin that was approved by the U.S. Food and Drug Administration to treat patients with relapsed or refractory disease.[19,20,21,22]

Evidence (moxetumomab pasudotox-tdfk):

1. Moxetumomab pasudotox-tdfk was given to 80 patients who were previously treated with at least two regimens.[23][Level of evidence: 3iiiDiv]
   • In a phase II trial, 75% of patients responded and 30% had a complete response.

Ibrutinib

Evidence (ibrutinib):

1. In a phase II study, reported in abstract form, 28 patients with refractory hairy cell leukemia had a 48% response rate to ibrutinib.[24][Level of evidence: 3iiiDiv]

Interferon-alpha

Interferon-alpha and splenectomy are therapeutic options that can be considered when other options have been exhausted (Refer to the section on Interferon-alpha in the Standard Treatment Options for Hairy Cell Leukemia section.)[25,26,27][Level of evidence: 3iiiDiv].

Splenectomy

Interferon-alpha and splenectomy are therapeutic options that can be considered when other options have been exhausted.[28][Level of evidence: 3iiiDiv]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

1. 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.
2. 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.
3. 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.
4. 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.
5. Gidron A, Tallman MS: 2-CdA in the treatment of hairy cell leukemia: a review of long-term follow-up. Leuk Lymphoma 47 (11): 2301-7, 2006.
6. Else M, Dearden CE, Matutes E, et al.: Long-term follow-up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosis. Br J Haematol 145 (6): 733-40, 2009.
7. Gerrie AS, Zypchen LN, Connors JM: Fludarabine and rituximab for relapsed or refractory hairy cell leukemia. Blood 119 (9): 1988-91, 2012.
8. 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.
9. 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.
10. Thomas DA, O'Brien S, Bueso-Ramos C, et al.: Rituximab in relapsed or refractory hairy cell leukemia. Blood 102 (12): 3906-11, 2003.
11. Angelopoulou MK, Pangalis GA, Sachanas S, et al.: Outcome and toxicity in relapsed hairy cell leukemia patients treated with rituximab. Leuk Lymphoma 49 (9): 1817-20, 2008.
12. Ravandi F, O'Brien S, Jorgensen J, et al.: Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia. Blood 118 (14): 3818-23, 2011.
13. Else M, Dearden CE, Matutes E, et al.: Rituximab with pentostatin or cladribine: an effective combination treatment for hairy cell leukemia after disease recurrence. Leuk Lymphoma 52 (Suppl 2): 75-8, 2011.
14. Chihara D, Kantarjian H, O'Brien S, et al.: Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial. Br J Haematol 174 (5): 760-6, 2016.
15. Chihara D, Arons E, Stetler-Stevenson M, et al.: Randomized Phase II Study of First-Line Cladribine With Concurrent or Delayed Rituximab in Patients With Hairy Cell Leukemia. J Clin Oncol 38 (14): 1527-1538, 2020.
16. Pettirossi V, Santi A, Imperi E, et al.: BRAF inhibitors reverse the unique molecular signature and phenotype of hairy cell leukemia and exert potent antileukemic activity. Blood 125 (8): 1207-16, 2015.
17. Tiacci E, Park JH, De Carolis L, et al.: Targeting Mutant BRAF in Relapsed or Refractory Hairy-Cell Leukemia. N Engl J Med 373 (18): 1733-47, 2015.
18. Dietrich S, Pircher A, Endris V, et al.: BRAF inhibition in hairy cell leukemia with low-dose vemurafenib. Blood 127 (23): 2847-55, 2016.
19. Kreitman RJ, Tallman MS, Robak T, et al.: Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up. Blood 131 (21): 2331-2334, 2018.
20. Kreitman RJ, Wilson WH, White JD, et al.: Phase I trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies. J Clin Oncol 18 (8): 1622-36, 2000.
21. Kreitman RJ, Stetler-Stevenson M, Margulies I, et al.: Phase II trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with hairy cell leukemia. J Clin Oncol 27 (18): 2983-90, 2009.
22. Kreitman RJ, Tallman MS, Robak T, et al.: Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia. J Clin Oncol 30 (15): 1822-8, 2012.
23. Kreitman RJ, Dearden C, Zinzani PL, et al.: Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia 32 (8): 1768-1777, 2018.
24. Jones J, Andritsos L, Kreitman RJ: Efficacy and safety of the Bruton tyrosine kinase inhibitor ibrutinib in patients with hairy cell leukemia: stage 1 results of a phase 2 study. [Abstract] Blood 128 (22): A-1215, 2016.
25. 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.
26. 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.
27. 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.
28. 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.

Changes to This Summary (12 / 17 / 2020)

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 Options for Hairy Cell Leukemia

Added text to state that in a randomized phase II study, 68 patients with previously untreated hairy cell leukemia were randomly assigned to receive cladribine 0.15 mg/kg intravenously on days 1 to 5 with 8 weekly doses of rituximab concurrently or after 6 months if still positive with minimal residual disease (MRD) testing. With a median follow-up of 96 months, 94% of patients who received concurrent therapy were MRD-free compared with 12% of patients who received delayed therapy [cited Chihara et al. as reference 9 and level of evidence 3iiiDiv).

Added text to state that MRD testing in this setting has never been validated as a clinically significant endpoint; this concept requires further study, but hairy cell leukemia is rare, with 600 to 800 new cases annually in the United States.

Relapsed or Refractory Hairy Cell Leukemia

Revised text to state that patients with hairy cell leukemia who relapse after the first course of cladribine or pentostatin often respond well to re-treatment with the same or another purine analog, especially if relapse occurs after 2 years.

Added text to state that vemurafenib can be given in combination with rituximab.

Added moxetumomab pasudotox-tdfk as a new subsection.

Added text to state that in a phase II study, reported in abstract form, 28 patients with refractory hairy cell leukemia had a 48% response rate to ibrutinib (cited Jones et al. as reference 24 and level of evidence: 3iiiDiv).

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of hairy cell leukemia. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Hairy Cell Leukemia Treatment are:

• Eric J. Seifter, MD (Johns Hopkins University)
• Mikkael A. Sekeres, MD, MS (Cleveland Clinic Taussig Cancer Institute)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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The preferred citation for this PDQ summary is:

PDQ® Adult Treatment Editorial Board. PDQ Hairy Cell Leukemia Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/leukemia/hp/hairy-cell-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389184]

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Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

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More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website's Email Us.

Last Revised: 2020-12-17