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Related Collections Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2002, Vol. 99, No. 10, pp. 3530-3539 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study Charles L. Sawyers, Andreas Hochhaus, Eric Feldman, John M. Goldman, Carole B. Miller, Oliver G. Ottmann, Charles A. Schiffer, Moshe Talpaz, Francois Guilhot, Michael W. N. Deininger, Thomas Fischer, Steve G. O'Brien, Richard M. Stone, Carlo B. Gambacorti-Passerini, Nigel H. Russell, Jose J. Reiffers, Thomas C. Shea, Bernard Chapuis, Steven Coutre, Sante Tura, Enrica Morra, Richard A. Larson, Alan Saven, Christian Peschel, Alois Gratwohl, Franco Mandelli, Monique Ben-Am, Insa Gathmann, Renaud Capdeville, Ronald L. Paquette, and Brian J. Druker From the Department of Medicine and Molecular Biology Institute, University of California, Los Angeles, CA; III. Medizinische Universitätsklinik Mannheim der Universität Heidelberg, Mannheim, Germany; New York Presbyterian Hospital-Weill Medical College of Cornell University, New York, NY; Department of Haematology, Hammersmith Hospital/ICSM, London, United Kingdom ; Johns Hopkins Oncology Center, Baltimore, MD; Medizinische Klinik III, Johann Wolfgang Goethe-Universität, Frankfurt, Germany; Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI; MD Anderson Cancer Center, Houston, TX; Department of Oncology, Hematology and Cell Therapy, CHU de Poitiers, Poitiers, France; Abteilung Haematologie/Onkologie, Universität Leipzig, Germany; Universitätsklinikum, 3. Medizinische Klinik und Poliklinik, Mainz, Germany; Department of Haematology, Royal Victoria Infirmary, University of Newcastle upon Tyne, United Kingdom; Dana Farber Cancer Institute, Boston, MA; Hematology Section, San Gerardo Hospital, Monza, and Department of Experimental Oncology, National Cancer Institute, Milano, Italy; Department of Haematology, City Hospital, Nottingham, United Kingdom; Laboratoire de Greffe de Moelle, Universite Victor Segalen, Bordeaux, France; Division of Hematology/Oncology, University of North Carolina, Chapel Hill; Division d'hématologie, Hopitâl cantonal universitaire, Geneva, Switzerland; Division of Hematology, Stanford University School of Medicine, Stanford, CA; Instituto di Ematologia, Ospedale Policlinicl Sant'Orsola-Malpighi, Bologna, Italy; Divisione di Ematologia, Azienda Ospedaliera Niguarda Ca'Granda, Milan, Italy; University of Chicago Medical Center, IL; Ida and Cecil Green Cancer Center, Scripps Clinic, La Jolla, CA; III. Medizinische Klinik und Poliklinik der TU, Haematologie/Onkologie, Munich, Germany; Division of Hematology, Universitätsklinik, Kantonspital, Basel, Switzerland; Dipartimento di Biotechologie Cedulari ed Ematologia, Azienda Policlinico Umberto 1, Universita La Sapienza, Rome, Italy; Novartis Pharmaceuticals, Basel, Switzerland; School of Medicine, University of California, Los Angeles, CA; and Division of Hematology, Oregon Health Sciences University, Portland, OR. Blast crisis is the most advanced stage of chronic myelogenous leukemia (CML) and is highly refractory to therapy. CML is caused by expression of the chimeric BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Imatinib (Glivec, formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl tyrosine kinase. A total of 260 patients with CML were enrolled in a phase II trial, of whom 229 had a confirmed diagnosis of CML in blast crisis. Patients were treated with imatinib in daily oral doses of 400 mg or 600 mg. Imatinib induced hematologic responses in 52% of patients and sustained hematologic responses lasting at least 4 weeks in 31% of patients, including complete hematologic responses in 8%. For patients with a sustained response, the estimated median response duration was 10 months. Imatinib induced major cytogenetic responses in 16% of patients, with 7% of the responses being complete. Median survival time was 6.9 months. Nonhematologic adverse reactions were frequent but generally mild or moderate. Episodes of severe cytopenia were also frequent and were attributable to the underlying condition and treatment with imatinib. Drug-related adverse events led to discontinuation of therapy in 5% of patients, most often because of cytopenia, skin disorders, or gastrointestinal reactions. These results demonstrate that imatinib has substantial activity and a favorable safety profile when used as a single agent in patients with CML in blast crisis. Additional clinical studies are warranted to explore the efficacy and feasibility of imatinib used in combination with other antileukemic drugs. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Wu, F. Meng, L.-Y. Kong, Z. Peng, Y. Ying, W. G. Bornmann, B. G. Darnay, B. Lamothe, H. Sun, M. Talpaz, et al. Association Between Imatinib-Resistant BCR-ABL Mutation-Negative Leukemia and Persistent Activation of LYN Kinase J Natl Cancer Inst, July 2, 2008; 100(13): 926 - 939. [Abstract] [Full Text] [PDF] R. Capdeville, T. Krahnke, A. Hatfield, J. M. Ford, I. Van Hoomissen, and I. 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