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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Byrd, J. C. Articles by White, C. A. Search for Related Content PubMed PubMed Citation Articles by Byrd, J. C. Articles by White, C. A.

Rituximab Therapy in Hematologic Malignancy Patients With Circulating Blood Tumor Cells: Association With Increased Infusion-Related Side Effects and Rapid Blood Tumor Clearance

From the Division of Hematology-Oncology, Walter Reed Army Medical Center, Washington, DC; Department of Medicine, Uniformed Services University of Health Sciences, Bethesda, MD; Division of Hematologic Malignancies, Johns Hopkins Oncology Center, Baltimore, MD; Genentech, Inc, South San Francisco, CA; Division of Hematology and Oncology, National Naval Medical Center, Bethesda, MD; and IDEC Pharmaceuticals Corporation, San Diego, CA.

Address reprint requests to John C. Byrd, MD, Director, Clinical Research, Hematology Oncology Service, Ward 78, Walter Reed Army Medical Center, 6900 Georgia Ave, NW, Washington, DC 20307; email john_c.byrd{at}wramaa.chcs.amedd army.mil

PURPOSE: Rituximab was recently approved for use in relapsed, low-grade non-Hodgkin's lymphoma; however, few data exist regarding the safety of this agent in patients with a high number of tumor cells in the blood.

METHODS AND RESULTS: After the observation at our institution of a rapid reduction of peripheral-blood tumor cells with associated severe pulmonary infusion-related toxicity in two patients with refractory hematologic malignancies, data on three additional cases were collected from physician-submitted reports of adverse events related to rituximab treatment. Five patients with hematologic malignancies possessing a high number of blood tumor cells were treated with rituximab and developed rapid tumor clearance. The median age was 68 years (range, 26 to 78 years). Patients were diagnosed with B-cell prolymphocytic leukemia (n = 2), chronic lymphocytic leukemia (n = 2), or transformed non-Hodgkin's lymphoma (n = 1). All of these patients had bulky adenopathy or organomegaly. All five patients developed a unique syndrome of severe infusion-related reactions, thrombocytopenia, rapid decrement in circulating tumor cell load, and mild electrolyte evidence of tumor lysis, and all required hospitalization. In addition, one patient developed ascites. These events resolved, and four patients were subsequently treated with rituximab without significant complications.

CONCLUSION: Rituximab administration in patients who have a high number of tumor cells in the blood may have an increased likelihood of severe initial infusion-related reactions. These data also suggest that rituximab may have activity in a variety of other lymphoid neoplasms, such as chronic lymphocytic leukemia and B-cell prolymphocytic leukemia.

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Army, U.S. Navy, or Department of Defense.

This article has been cited by other articles:

				T. Tawara, K. Hasegawa, Y. Sugiura, K. Harada, T. Miura, S. Hayashi, T. Tahara, M. Ishikawa, H. Yoshida, K. Kubo, et al. Complement Activation Plays a Key Role in Antibody-Induced Infusion Toxicity in Monkeys and Rats J. Immunol., February 15, 2008; 180(4): 2294 - 2298. [Abstract] [Full Text] [PDF]

				J. Hayslip and R. Fenning Safe Administration of Iodine-131 Tositumomab After Repeated Infusion-Related Reactions to Rituximab Oncologist, March 1, 2007; 12(3): 338 - 340. [Abstract] [Full Text] [PDF]

				J. C. Byrd, T. S. Lin, J. T. Dalton, D. Wu, M. A. Phelps, B. Fischer, M. Moran, K. A. Blum, B. Rovin, M. Brooker-McEldowney, et al. Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia Blood, January 15, 2007; 109(2): 399 - 404. [Abstract] [Full Text] [PDF]

				N. Lamanna, M. Kalaycio, P. Maslak, J. G. Jurcic, M. Heaney, R. Brentjens, A. D. Zelenetz, D. Horgan, A. Gencarelli, K. S. Panageas, et al. Pentostatin, Cyclophosphamide, and Rituximab Is an Active, Well-Tolerated Regimen for Patients With Previously Treated Chronic Lymphocytic Leukemia J. Clin. Oncol., April 1, 2006; 24(10): 1575 - 1581. [Abstract] [Full Text] [PDF]

				K. A. Keogh, S. R. Ytterberg, F. C. Fervenza, K. A. Carlson, D. R. Schroeder, and U. Specks Rituximab for Refractory Wegener's Granulomatosis: Report of a Prospective, Open-Label Pilot Trial Am. J. Respir. Crit. Care Med., January 15, 2006; 173(2): 180 - 187. [Abstract] [Full Text] [PDF]

				A. Ribas, L. H. Camacho, G. Lopez-Berestein, D. Pavlov, C. A. Bulanhagui, R. Millham, B. Comin-Anduix, J. M. Reuben, E. Seja, C. A. Parker, et al. Antitumor Activity in Melanoma and Anti-Self Responses in a Phase I Trial With the Anti-Cytotoxic T Lymphocyte-Associated Antigen 4 Monoclonal Antibody CP-675,206 J. Clin. Oncol., December 10, 2005; 23(35): 8968 - 8977. [Abstract] [Full Text] [PDF]

				C. M. Ng, R. Bruno, D. Combs, and B. Davies Population Pharmacokinetics of Rituximab (Anti-CD20 Monoclonal Antibody) in Rheumatoid Arthritis Patients During a Phase II Clinical Trial J. Clin. Pharmacol., July 1, 2005; 45(7): 792 - 801. [Abstract] [Full Text] [PDF]

				M.S. Czuczman, A. Koryzna, A. Mohr, C. Stewart, K. Donohue, L. Blumenson, Z.P. Bernstein, P. McCarthy, A. Alam, F. Hernandez-Ilizaliturri, et al. Rituximab in Combination With Fludarabine Chemotherapy in Low-Grade or Follicular Lymphoma J. Clin. Oncol., February 1, 2005; 23(4): 694 - 704. [Abstract] [Full Text] [PDF]

				A. J. Olszewski and M. L. Grossbard Empowering Targeted Therapy: Lessons from Rituximab Sci. Signal., July 13, 2004; 2004(241): pe30 - pe30. [Abstract] [Full Text] [PDF]

				M. Zecca, B. Nobili, U. Ramenghi, S. Perrotta, G. Amendola, P. Rosito, M. Jankovic, P. Pierani, P. De Stefano, M. R. Bonora, et al. Rituximab for the treatment of refractory autoimmune hemolytic anemia in children Blood, May 15, 2003; 101(10): 3857 - 3861. [Abstract] [Full Text] [PDF]

				B. Mavromatis and B. D. Cheson Monoclonal Antibody Therapy of Chronic Lymphocytic Leukemia J. Clin. Oncol., May 1, 2003; 21(9): 1874 - 1881. [Abstract] [Full Text] [PDF]

				S. Faderl, D. A. Thomas, S. O'Brien, G. Garcia-Manero, H. M. Kantarjian, F. J. Giles, C. Koller, A. Ferrajoli, S. Verstovsek, B. Pro, et al. Experience with alemtuzumab plus rituximab in patients with relapsed and refractory lymphoid malignancies Blood, May 1, 2003; 101(9): 3413 - 3415. [Abstract] [Full Text] [PDF]

				H. Schulz, S. K. Klein, U. Rehwald, M. Reiser, A. Hinke, W.-U. Knauf, W.-E. Aulitzky, M. Hensel, M. Herold, D. Huhn, et al. Phase 2 study of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia Blood, October 16, 2002; 100(9): 3115 - 3120. [Abstract] [Full Text] [PDF]

				R. O. Dillman Radiolabeled Anti-CD20 Monoclonal Antibodies for the Treatment of B-Cell Lymphoma J. Clin. Oncol., August 15, 2002; 20(16): 3545 - 3557. [Full Text] [PDF]

				T. Igarashi, Y. Kobayashi, M. Ogura, T. Kinoshita, T. Ohtsu, Y. Sasaki, Y. Morishima, T. Murate, M. Kasai, N. Uike, et al. Factors affecting toxicity, response and progression-free survival in relapsed patients with indolent B-cell lymphoma and mantle cell lymphoma treated with rituximab: a Japanese phase II study Ann. Onc., June 1, 2002; 13(6): 928 - 943. [Abstract] [Full Text] [PDF]

				A. Countouriotis, T. B. Moore, and K. M. Sakamoto Cell Surface Antigen and Molecular Targeting in the Treatment of Hematologic Malignancies Stem Cells, May 1, 2002; 20(3): 215 - 229. [Abstract] [Full Text] [PDF]

				J. Golay, M. Lazzari, V. Facchinetti, S. Bernasconi, G. Borleri, T. Barbui, A. Rambaldi, and M. Introna CD20 levels determine the in vitro susceptibility to rituximab and complement of B-cell chronic lymphocytic leukemia: further regulation by CD55 and CD59 Blood, December 1, 2001; 98(12): 3383 - 3389. [Abstract] [Full Text] [PDF]

				V. Kunzmann, T. Ruediger, M. Hallek, H.-K. Mueller-Hermelink, and M. Wilhelm Tumor cell agglutination and not solely cytokine release as mechanism of adverse reactions during anti-CD20 monoclonal antibody (IDEC-C2B8, rituximab) treatment Blood, September 15, 2001; 98(6): 1991 - 1992. [Full Text] [PDF]

				D. Huhn, C. von Schilling, M. Wilhelm, A. D. Ho, M. Hallek, R. Kuse, W. Knauf, U. Riedel, A. Hinke, S. Srock, et al. Rituximab therapy of patients with B-cell chronic lymphocytic leukemia Blood, September 1, 2001; 98(5): 1326 - 1331. [Abstract] [Full Text] [PDF]

				M. Zecca, P. De Stefano, B. Nobili, and F. Locatelli Anti-CD20 monoclonal antibody for the treatment of severe, immune-mediated, pure red cell aplasia and hemolytic anemia Blood, June 15, 2001; 97(12): 3995 - 3997. [Abstract] [Full Text] [PDF]

				J. C. Byrd, T. Murphy, R. S. Howard, M. S. Lucas, A. Goodrich, K. Park, M. Pearson, J. K. Waselenko, G. Ling, M. R. Grever, et al. Rituximab Using A Thrice Weekly Dosing Schedule in B-Cell Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma Demonstrates Clinical Activity and Acceptable Toxicity J. Clin. Oncol., April 15, 2001; 19(8): 2153 - 2164. [Abstract] [Full Text] [PDF]

				O. W. Press, J. P. Leonard, B. Coiffier, R. Levy, and J. Timmerman Immunotherapy of Non-Hodgkin's Lymphomas Hematology, January 1, 2001; 2001(1): 221 - 240. [Abstract] [Full Text] [PDF]

				P. Colombat, G. Salles, N. Brousse, P. Eftekhari, P. Soubeyran, V. Delwail, E. Deconinck, C. Haioun, C. Foussard, C. Sebban, et al. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation Blood, January 1, 2001; 97(1): 101 - 106. [Abstract] [Full Text] [PDF]

				J. D. Hainsworth Monoclonal Antibody Therapy in Lymphoid Malignancies Oncologist, October 1, 2000; 5(5): 376 - 384. [Abstract] [Full Text]

				U. Winkler, M. Jensen, O. Manzke, H. Schulz, V. Diehl, and A. Engert Cytokine-Release Syndrome in Patients With B-Cell Chronic Lymphocytic Leukemia and High Lymphocyte Counts After Treatment With an Anti-CD20 Monoclonal Antibody (Rituximab, IDEC-C2B8) Blood, October 1, 1999; 94(7): 2217 - 2224. [Abstract] [Full Text] [PDF]