This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rai, K. R. Articles by Brettman, L. Search for Related Content PubMed PubMed Citation Articles by Rai, K. R. Articles by Brettman, L. Social Bookmarking                            What's this?

Alemtuzumab in Previously Treated Chronic Lymphocytic Leukemia Patients Who Also Had Received Fludarabine

From the Long Island Jewish Medical Center, New Hyde Park, NY; Georgetown University Medical Center, Lombardi Cancer Center, Washington, DC; Marshfield Clinic, Marshfield, WI; Wake Forest University Baptist Medical Center, Winston-Salem, and University of North Carolina at Chapel Hill, Chapel Hill, NC; University of Pennsylvania Medical Center, Philadelphia, PA; Ilex Oncology, San Antonio, TX; and Millennium Pharmaceuticals, Cambridge, MA.

This work was presented in part at the Forty-Second Annual Meeting of the American Society of Hematology, San Francisco, CA, December 1-5, 2000.Address reprint requests to K.R. Rai, Long Island Jewish Medical Center, New Hyde Park, New York, NY 11040; email: rai{at}lij.edu

PURPOSE: This phase II pilot study determined the efficacy and safety of alemtuzumab (Campath-1H; Burroughs Wellcome, United Kingdom) in patients with chronic lymphocytic leukemia (CLL), all of whom had previously received fludarabine and other chemotherapy regimens.

PATIENTS AND METHODS: Twenty-four patients were treated with intravenous alemtuzumab at six centers in the United States. The target dose of 30 mg over 2 hours, three times weekly, was administered for up to 16 weeks. Responses were evaluated by an independent panel of experts using 1996 National Cancer Institute–sponsored Working Group criteria. Safety assessments included analysis of lymphocyte subpopulations. Antimicrobial prophylaxis was not mandatory.

RESULTS: Eight patients (33%) achieved a major response (all partial remissions), with a median time to response of 3.9 months (range, 1.6 to 5.3 months). The median duration of response was 15.4 months (range, 4.6 to 38.0 months), the median time to disease progression was 19.6 months (range, 7.7 to 42.0 months), and the median survival time was 35.8 months (range, 8.8 to 47.1 months). Acute infusion-related events, mainly grades 1 and 2, were most common and most severe in the first week. Ten patients (eight nonresponders and two responders) experienced major infections on-study. Pneumocystis carinii pneumonia was reported in two patients on-study; neither had received prophylaxis. Median CD4⁺ and CD8⁺ counts decreased and then began to increase by the end of the study, with further recovery by 1-month follow-up. One of 53 samples obtained from 10 patients had a low titer of alemtuzumab antibodies.

CONCLUSION: Alemtuzumab has significant activity in poor-prognosis, fludarabine-treated CLL patients. However, because of a relatively high incidence of opportunistic infections accompanying profound lymphopenia, future protocols should include mandatory prophylaxis.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				T. Elter, J. Kilp, P. Borchmann, H. Schulz, M. Hallek, and A. Engert Pharmacokinetics of alemtuzumab in combination with fludarabine in patients with relapsed or refractory B-cell chronic lymphocytic leukemia Haematologica, January 1, 2009; 94(1): 150 - 152. [Full Text] [PDF]

				C Agostinelli, P P Piccaluga, P Went, M Rossi, A Gazzola, S Righi, T Sista, C Campidelli, P L Zinzani, B Falini, et al. Peripheral T cell lymphoma, not otherwise specified: the stuff of genes, dreams and therapies J. Clin. Pathol., November 1, 2008; 61(11): 1160 - 1167. [Abstract] [Full Text] [PDF]

				S. O'Brien, F. Ravandi, T. Riehl, W. Wierda, X. Huang, J. Tarrand, B. O'Neal, H. Kantarjian, and M. Keating Valganciclovir prevents cytomegalovirus reactivation in patients receiving alemtuzumab-based therapy Blood, February 15, 2008; 111(4): 1816 - 1819. [Abstract] [Full Text] [PDF]

				S. Baskar, K. Y. Kwong, T. Hofer, J. M. Levy, M. G. Kennedy, E. Lee, L. M. Staudt, W. H. Wilson, A. Wiestner, and C. Rader Unique Cell Surface Expression of Receptor Tyrosine Kinase ROR1 in Human B-Cell Chronic Lymphocytic Leukemia Clin. Cancer Res., January 15, 2008; 14(2): 396 - 404. [Abstract] [Full Text] [PDF]

				W. G. Wierda Treatments for Patients with Chronic Lymphocytic Leukemia ASCO Educational Book, January 1, 2008; 2008(1): 297 - 305. [Abstract] [Full Text] [PDF]

				J. C. Byrd, S. O'Brien, I. W. Flinn, T. J. Kipps, M. Weiss, K. Rai, T. S. Lin, J. Woodworth, D. Wynne, J. Reid, et al. Phase 1 Study of Lumiliximab with Detailed Pharmacokinetic and Pharmacodynamic Measurements in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia Clin. Cancer Res., August 1, 2007; 13(15): 4448 - 4455. [Abstract] [Full Text] [PDF]

				P. P. Piccaluga, C. Agostinelli, S. Righi, P. L. Zinzani, and S. A. Pileri Expression of CD52 in peripheral T-cell lymphoma Haematologica, April 1, 2007; 92(4): 566 - 567. [Abstract] [Full Text] [PDF]

				J. A. McEarchern, E. Oflazoglu, L. Francisco, C. F. McDonagh, K. A. Gordon, I. Stone, K. Klussman, E. Turcott, N. van Rooijen, P. Carter, et al. Engineered anti-CD70 antibody with multiple effector functions exhibits in vitro and in vivo antitumor activities Blood, February 1, 2007; 109(3): 1185 - 1192. [Abstract] [Full Text] [PDF]

				V. A. Morrison Management of Infectious Complications in Patients with Chronic Lymphocytic Leukemia Hematology, January 1, 2007; 2007(1): 332 - 338. [Abstract] [Full Text] [PDF]

				K. W. L. Yee and S. M. O'Brien Chronic Lymphocytic Leukemia: Diagnosis and Treatment Mayo Clin. Proc., August 1, 2006; 81(8): 1105 - 1129. [Abstract] [Full Text] [PDF]

				M. Sandherr, H. Einsele, H. Hebart, C. Kahl, W. Kern, M. Kiehl, G. Massenkeil, O. Penack, X. Schiel, S. Schuettrumpf, et al. Antiviral prophylaxis in patients with haematological malignancies and solid tumours: Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Oncology (DGHO) Ann. Onc., July 1, 2006; 17(7): 1051 - 1059. [Abstract] [Full Text] [PDF]

				E. Montserrat, C. Moreno, J. Esteve, A. Urbano-Ispizua, E. Gine, and F. Bosch How I treat refractory CLL Blood, February 15, 2006; 107(4): 1276 - 1283. [Abstract] [Full Text] [PDF]

				W. G. Wierda Current and Investigational Therapies for Patients with CLL Hematology, January 1, 2006; 2006(1): 285 - 294. [Abstract] [Full Text] [PDF]

				T. Elter, P. Borchmann, H. Schulz, M. Reiser, S. Trelle, R. Schnell, M. Jensen, P. Staib, T. Schinkothe, H. Stutzer, et al. Fludarabine in Combination With Alemtuzumab Is Effective and Feasible in Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia: Results of a Phase II Trial J. Clin. Oncol., October 1, 2005; 23(28): 7024 - 7031. [Abstract] [Full Text] [PDF]

				E. T. Wong Management of Central Nervous System Lymphomas Using Monoclonal Antibodies: Challenges and Opportunities Clin. Cancer Res., October 1, 2005; 11(19): 7151s - 7157s. [Abstract] [Full Text] [PDF]

				W. G. Wierda, T. J. Kipps, and M. J. Keating Novel Immune-Based Treatment Strategies for Chronic Lymphocytic Leukemia J. Clin. Oncol., September 10, 2005; 23(26): 6325 - 6332. [Abstract] [Full Text] [PDF]

				W. Wierda, S. O'Brien, S. Wen, S. Faderl, G. Garcia-Manero, D. Thomas, K.-A. Do, J. Cortes, C. Koller, M. Beran, et al. Chemoimmunotherapy With Fludarabine, Cyclophosphamide, and Rituximab for Relapsed and Refractory Chronic Lymphocytic Leukemia J. Clin. Oncol., June 20, 2005; 23(18): 4070 - 4078. [Abstract] [Full Text] [PDF]

				P. Moreton, B. Kennedy, G. Lucas, M. Leach, S. M.B. Rassam, A. Haynes, J. Tighe, D. Oscier, C. Fegan, A. Rawstron, et al. Eradication of Minimal Residual Disease in B-Cell Chronic Lymphocytic Leukemia After Alemtuzumab Therapy Is Associated With Prolonged Survival J. Clin. Oncol., May 1, 2005; 23(13): 2971 - 2979. [Abstract] [Full Text] [PDF]

				M. Hallek and On Behalf Of The German CLL Study Group Chronic Lymphocytic Leukemia (CLL): First-Line Treatment Hematology, January 1, 2005; 2005(1): 285 - 291. [Abstract] [Full Text] [PDF]

				T. S. Lin, I. W. Flinn, R. Modali, T. A. Lehman, J. Webb, S. Waymer, M. E. Moran, M. S. Lucas, S. S. Farag, and J. C. Byrd FCGR3A and FCGR2A polymorphisms may not correlate with response to alemtuzumab in chronic lymphocytic leukemia Blood, January 1, 2005; 105(1): 289 - 291. [Abstract] [Full Text] [PDF]

				G. Hale, P. Rebello, L. R. Brettman, C. Fegan, B. Kennedy, E. Kimby, M. Leach, J. Lundin, H. Mellstedt, P. Moreton, et al. Blood concentrations of alemtuzumab and antiglobulin responses in patients with chronic lymphocytic leukemia following intravenous or subcutaneous routes of administration Blood, August 15, 2004; 104(4): 948 - 955. [Abstract] [Full Text] [PDF]

				A. C. Rawstron, B. Kennedy, P. Moreton, A. J. Dickinson, M. J. Cullen, S. J. Richards, A. S. Jack, and P. Hillmen Early prediction of outcome and response to alemtuzumab therapy in chronic lymphocytic leukemia Blood, March 15, 2004; 103(6): 2027 - 2031. [Abstract] [Full Text] [PDF]

				A. L. Basquiera, A. R. Berretta, J. J. Garcia, and E. D. Palazzo Coronary ischemia related to alemtuzumab therapy Ann. Onc., March 1, 2004; 15(3): 539 - 540. [Full Text] [PDF]

				M. R. Muller, G. Tsakou, F. Grunebach, S. M. Schmidt, and P. Brossart Induction of chronic lymphocytic leukemia (CLL)-specific CD4- and CD8-mediated T-cell responses using RNA-transfected dendritic cells Blood, March 1, 2004; 103(5): 1763 - 1769. [Abstract] [Full Text] [PDF]

				I. M. Ghobrial, L. A. Otteman, W. L. White, D. A. Rizzieri, S. Weitman, and D. M. Vaughn An EBV-Positive Lymphoproliferative Disorder after Therapy with Alemtuzumab N. Engl. J. Med., December 25, 2003; 349(26): 2570 - 2572. [Full Text] [PDF]

				M. Coleman, D. M. Goldenberg, A. B. Siegel, J. C. Ketas, M. Ashe, J. M. Fiore, and J. P. Leonard Epratuzumab: Targeting B-Cell Malignancies through CD22 Clin. Cancer Res., September 1, 2003; 9(10): 3991S - 3994. [Abstract] [Full Text] [PDF]

				S. Kumar, T. K. Kimlinger, J. A. Lust, K. Donovan, and T. E. Witzig Expression of CD52 on plasma cells in plasma cell proliferative disorders Blood, August 1, 2003; 102(3): 1075 - 1077. [Abstract] [Full Text] [PDF]