Hairy cell leukemia (HCL) is a rare, chronic, B-cell, lymphoproliferative disorder. Treatment has been revolutionized by the advent of interferon (IFN)-α and purine analogs (PA). First-line therapy with PA yields complete response rates of 75–100%, with many long-lasting remissions. In the event of profound neutropenia and/or infectious complications, a short sequence of IFN-α may precede PA treatment. Because of the excellent results achieved with PA therapy, the potential role of rituximab (an anti-CD20 monoclonal antibody that is highly effective against most B-cell lymphomas) in HCL has yet to be elucidated. Six HCL cases treated with rituximab are reported herein with a view to elucidating the potential role of the drug in HCL. The indications essentially consist of relapsing or refractory disease, avoiding the cumulative toxicity of PA, consolidation therapy in order to eradicate minimal residual disease, and first-line therapy for patients with contraindications to PA and IFN-α.

Malfuson JV, Gisserot O, Cremades S, Doghmi K, Fagot T, Souleau B, de Revel T, de Jaureguiberry JP, Nedellec G: Hairy-cell leukemia: 30 cases and a review of the literature (in French). Ann Med Interne (Paris) 2003;154:435–440.
Ratain MJ, Golomb HM, Vardiman JW, Westbrook CA, Barker C, Hooberman A, Bitter MA, Daly K: Relapse after interferon alfa-2b therapy for hairy-cell leukemia: analysis of prognostic variables. J Clin Oncol 1988;6:1714–1721.
Mey U, Strehl J, Gorschluter M, Ziske C, Glasmacher A, Pralle H, Schmidt-Wolf I: Advances in the treatment of hairy-cell leukaemia. Lancet Oncol 2003;4:86–94.
Filleul B, Delannoy A, Ferrant A, Zenebergh A, Van Daele S, Bosly A, Doyen C, Mineur P, Glorieux P, Driesschaert P, Sokal G, Martiat P, Michaux JL: A single course of 2-chloro-deoxyadenosine does not eradicate leukemic cells in hairy cell leukemia patients in complete remission. Leukemia 1994;8:1153–1156.
Thaler J, Grunewald K, Gattringer C, Ho AD, Weyrer K, Dietze O, Stauder R, Fluckinger T, Lang A, Huber H: Long-term follow-up of patients with hairy cell leukaemia treated with pentostatin: lymphocyte subpopulations and residual bone marrow infiltration. Br J Haematol 1993;84:75–82.
Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C: CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002;346:235–242.
Davis TA, White CA, Grillo-Lopez AJ, Velasquez WS, Link B, Maloney DG, Dillman RO, Williams ME, Mohrbacher A, Weaver R, Dowden S, Levy R: Single-agent monoclonal antibody efficacy in bulky non-Hodgkin’s lymphoma: results of a phase II trial of rituximab. J Clin Oncol 1999;17:1851–1857.
Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, Reiser M, Metzner B, Harder H, Hegewisch-Becker S, Fischer T, Kropff M, Reis HE, Freund M, Wormann B, Fuchs R, Planker M, Schimke J, Eimermacher H, Trumper L, Aldaoud A, Parwaresch R, Unterhalt M: Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2005;106:3725–3732.
Robbins BA, Ellison DJ, Spinosa JC, Carey CA, Lukes RJ, Poppema S, Saven A, Piro LD: Diagnostic application of two-color flow cytometry in 161 cases of hairy cell leukemia. Blood 1993;82:1277–1287.
Hagberg H: Chimeric monoclonal anti-CD20 antibody (rituximab) – an effective treatment for a patient with relapsing hairy cell leukaemia. Med Oncol 1999;16:221–222.
Hagberg H, Lundholm L: Rituximab, a chimaeric anti-CD20 monoclonal antibody, in the treatment of hairy cell leukaemia. Br J Haematol 2001;115:609–611.
Lauria F, Lenoci M, Annino L, Raspadori D, Marotta G, Bocchia M, Forconi F, Gentili S, La Manda M, Marconcini S, Tozzi M, Baldini L, Zinzani PL, Foa R: Efficacy of anti-CD20 monoclonal antibodies (Mabthera) in patients with progressed hairy cell leukemia. Haematologica 2001;86:1046–1050.
Nieva J, Bethel K, Saven A: Phase 2 study of rituximab in the treatment of cladribine-failed patients with hairy cell leukemia. Blood 2003;102:810–813.
Thomas DA, O’Brien S, Bueso-Ramos C, Faderl S, Keating MJ, Giles FJ, Cortes J, Kantarjian HM: Rituximab in relapsed or refractory hairy cell leukemia. Blood 2003;102:3906–3911.
Zenhausern R, Simcock M, Gratwohl A, Hess U, Bargetzi M, Tobler A: Rituximab in patients with hairy cell leukemia relapsing after treatment with 2-chlorodeoxyadenosine (SAKK 31/98). Haematologica 2008;93:1426–1428.
Angelopoulou MK, Pangalis GA, Sachanas S, Kokoris SI, Anargyrou K, Galani Z, Kalpadakis C, Vassilakopoulos TP: Outcome and toxicity in relapsed hairy cell leukemia patients treated with rituximab. Leuk Lymphoma 2008;49:1817–1820.
Else M, Osuji N, Forconi F, Dearden C, Del Giudice I, Matutes E, Wotherspoon A, Lauria F, Catovsky D: The role of rituximab in combination with pentostatin or cladribine for the treatment of recurrent/refractory hairy cell leukemia. Cancer 2007;110:2240–2247.
Cervetti G, Galimberti S, Andreazzoli F, Fazzi R, Cecconi N, Caracciolo F, Petrini M: Rituximab as treatment for minimal residual disease in hairy cell leukaemia. Eur J Haematol 2004;73:412–417.
Ravandi F, Jorgensen JL, O’Brien SM, Verstovsek S, Koller CA, Faderl S, Giles FJ, Ferrajoli A, Wierda WG, Odinga S, Huang X, Thomas DA, Freireich EJ, Jones D, Keating MJ, Kantarjian HM: Eradication of minimal residual disease in hairy cell leukemia. Blood 2006;107:4658–4662.
Narat S, Gandla J, Dogan A, Mehta A: Successful treatment of hairy cell leukemia variant with rituximab. Leuk Lymphoma 2005;46:1229–1232.
Flandrin G, Sigaux F, Sebahoun G, Bouffette P: Hairy cell leukemia: clinical presentation and follow-up of 211 patients. Semin Oncol 1984;11(4 suppl 2):458–471.
Belani R, Saven A: Cladribine in hairy cell leukemia. Hematol Oncol Clin North Am 2006;20:1109–1123.
Jansen J, Hermans J: Splenectomy in hairy cell leukemia: a retrospective multicenter analysis. Cancer 1981;47:2066–2076.
Quesada JR, Reuben J, Manning JT, Hersh EM, Gutterman JU: Alpha interferon for induction of remission in hairy-cell leukemia. N Engl J Med 1984;310:15–18.
Worman CP, Catovsky D, Bevan PC, Camba L, Joyner M, Green PJ, Williams HJ, Bottomley JM, Gordon-Smith EC, Cawley JC: Interferon is effective in hairy-cell leukaemia. Br J Haematol 1985;60:759–763.
Lauria F, Benfenati D, Raspadori D, Rondelli D, Ventura MA, Pileri S, Sabattini E, Poggi S, Benni M, Tura S: Retreatment with 2-CdA of progressed HCL patients. Leuk Lymphoma 1994;14(suppl 1):143–145.
Cheson BD: Infectious and immunosuppressive complications of purine analog therapy. J Clin Oncol 1995;13:2431–2448.
Legrand O, Vekhoff A, Marie JP, Zittoun R, Delmer A: Treatment of hairy cell leukaemia (HCL) with 2-chlorodeoxyadenosine (2-CdA): identification of parameters predictive of adverse effects. Br J Haematol 1997;99:165–167.
Flinn IW, Kopecky KJ, Foucar MK, Head D, Bennett JM, Hutchison R, Corbett W, Cassileth P, Habermann T, Golomb H, Rai K, Eisenhauer E, Appelbaum F, Cheson B, Grever MR: Long-term follow-up of remission duration, mortality, and second malignancies in hairy cell leukemia patients treated with pentostatin. Blood 2000;96:2981–2986.
Dearden CE, Matutes E, Hilditch BL, Swansbury GJ, Catovsky D: Long-term follow-up of patients with hairy cell leukaemia after treatment with pentostatin or cladribine. Br J Haematol 1999;106:515–519.
Wheaton S, Tallman MS, Hakimian D, Peterson L: Minimal residual disease may predict bone marrow relapse in patients with hairy cell leukemia treated with 2-chlorodeoxyadenosine. Blood 1996;87:1556–1560.
Matutes E, Meeus P, McLennan K, Catovsky D: The significance of minimal residual disease in hairy cell leukaemia treated with deoxycoformycin: a long-term follow-up study. Br J Haematol 1997;98:375–383.
Cervetti G, Galimberti S, Andreazzoli F, Fazzi R, Cecconi N, Caracciolo F, Petrini M: Rituximab as treatment for minimal residual disease in hairy cell leukaemia: extended follow-up. Br J Haematol 2008;143:296–298.
Di Gaetano N, Xiao Y, Erba E, Bassan R, Rambaldi A, Golay J, Introna M: Synergism between fludarabine and rituximab revealed in a follicular lymphoma cell line resistant to the cytotoxic activity of either drug alone. Br J Haematol 2001;114:800–809.
Byrd JC, Peterson BL, Morrison VA, Park K, Jacobson R, Hoke E, Vardiman JW, Rai K, Schiffer CA, Larson RA: Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712). Blood 2003;101:6–14.
Forconi F, Toraldo F, Sozzi E, Amato T, Raspadori D, Lauria F: Complete molecular remission induced by concomitant cladribine-rituximab treatment in a case of multi-resistant hairy cell leukemia. Leuk Lymphoma 2007;48:2441–2443.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.