SEARCH:   Advanced

Blood, 1 September 2006, Vol. 108, No. 5, pp. 1469-1477. Prepublished online as a Blood First Edition Paper on April 25, 2006; DOI 10.1182/blood-2005-11-4386. This Article Full Text (PDF) All Versions of this Article: 2005-11-4386v1 108/5/1469    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wassmann, B. Articles by Ottmann, O. G Search for Related Content PubMed PubMed Citation Articles by Wassmann, B. Articles by Ottmann, O. G Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 7, 2005 Accepted March 10, 2006 Alternating versus concurrent schedules of Imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL) Barbara Wassmann, Heike Pfeifer, Nicola Goekbuget, Dietrich W Beelen, Joachim Beck, Matthias Stelljes, Martin Bornhauser, Albrecht Reichle, Jolanta Perz, Rainer Haas, Arnold Ganser, Mathias Schmid, Lothar Kanz, Georg Lenz, Martin Kaufmann, Anja Binckebanck, Patrick Bruck, Regina Reutzel, Harald Gschaidmeier, Stefan Schwartz, Dieter Hoelzer, and Oliver G Ottmann* Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany Clinic for Bone Marrow Transplantation, Universitatsklinikum Essen, Essen, Germany Hematology and Oncology, Johannes Gutenberg-Universitat, Mainz, Germany Hematology and Oncology, Universitatsklinikum Munster, Munster, Germany Hematology and Oncology, Universitatsklinikum Carl Gustav Carus, Dresden, Germany Hematology and Oncology, Universitatsklinikum Regensburg, Regensburg, Germany Hematology and Oncology, Universitat Heidelberg, Heidelberg, Germany Hematology and Oncology, Heinrich Heine Universitat, Dusseldorf, Germany Hematology and Oncology, Medizinische Hochschule Hannover, Hannover, Germany Hematology and Oncology, Universitat Ulm, Ulm, Germany Hematology and Oncology, Eberhardt-Karls-Universitat, Tubingen, Germany Hematology and Oncology, Klinikum Grosshadern der Ludwig Maximilians Universitat, Munich, Germany Hematology and Oncology, Robert-Bosch-Krankenhaus, Stuttgart, Germany; Oncology, Novartis Pharma GmbH, Nurnberg, Germany Oncology, Novartis Pharma GmbH, Nurnberg, Germany Hematology and Oncology, Charite, Campus Benjamin Franklin, Berlin, Germany * Corresponding author; email: ottmann{at}em.uni-frankfurt.de. The best strategy for incorporating imatinib in front-line treatment of Ph+ALL has not been established. We enrolled 92 patients with newly diagnosed Ph+ALL in a prospective, multicenter study to investigate sequentially two treatment schedules with imatinib administered concurrent to or alternating with a uniform induction and consolidation regimen. Coadministration of imatinib and induction cycle 2 (INDII) resulted in a complete remission (CR) rate of 95% and PCR negativity for BCR-ABL in 52% of patients, compared to 19% in patients in the alternating treatment cohort (p=0.01). Remarkably, patients with and without a CR after induction cycle 1 (INDI) had similar hematologic and molecular responses after concurrent imatinib and INDII. In the concurrent cohort, grade III/V cytopenias and transient hepatotoxicity necessitated interruption of induction in 87% and 53% of patients, respectively; however, duration of induction was not prolonged when compared to patients receiving chemotherapy alone. No imatinib-related severe hematologic or non-hematologic toxicities were noted with the alternating schedule. In each cohort, 77% of patients underwent allogeneic stem cell transplantation (SCT) in first CR (CR1). Both schedules of imatinib have acceptable toxicity and facilitate SCT in CR1 in the majority of patients, but concurrent administration of imatinib and chemotherapy has greater antileukemic efficacy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. R. Schultz, W. P. Bowman, A. Aledo, W. B. Slayton, H. Sather, M. Devidas, C. Wang, S. M. Davies, P. S. Gaynon, M. Trigg, et al. Improved Early Event-Free Survival With Imatinib in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Children's Oncology Group Study J. Clin. Oncol., November 1, 2009; 27(31): 5175 - 5181. [Abstract] [Full Text] [PDF] A. K. Fielding, J. M. Rowe, S. M. Richards, G. Buck, A. V. Moorman, I. J. Durrant, D. I. Marks, A. K. McMillan, M. R. Litzow, H. M. Lazarus, et al. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993 Blood, May 7, 2009; 113(19): 4489 - 4496. [Abstract] [Full Text] [PDF] P. Bader, H. Kreyenberg, G. H.R. Henze, C. Eckert, M. Reising, A. Willasch, A. Barth, A. Borkhardt, C. Peters, R. Handgretinger, et al. Prognostic Value of Minimal Residual Disease Quantification Before Allogeneic Stem-Cell Transplantation in Relapsed Childhood Acute Lymphoblastic Leukemia: The ALL-REZ BFM Study Group J. Clin. Oncol., January 20, 2009; 27(3): 377 - 384. [Abstract] [Full Text] [PDF] D. Hoelzer and N. Gokbuget Allogeneic Stem Cell Transplant in Acute Lymphoblastic Leukemia: Who and When? ASCO Educational Book, January 1, 2009; 2009(1): 355 - 359. [Abstract] [Full Text] [PDF] S. M. O'Brien, D. A. Thomas, and S. Faderl A La Carte Therapy of Specific Acute Lymphocytic Leukemia Subsets ASCO Educational Book, January 1, 2009; 2009(1): 365 - 370. [Abstract] [Full Text] [PDF] M. Yanada, J. Takeuchi, I. Sugiura, H. Akiyama, N. Usui, F. Yagasaki, K. Nishii, Y. Ueda, M. Takeuchi, S. Miyawaki, et al. Karyotype at diagnosis is the major prognostic factor predicting relapse-free survival for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib-combined chemotherapy Haematologica, February 1, 2008; 93(2): 287 - 290. [Abstract] [Full Text] [PDF] M. Wetzler Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia: On Target to Improve Outcome ASCO Educational Book, January 1, 2008; 2008(1): 275 - 279. [Abstract] [Full Text] [PDF] G. J.L. Kaspers and C. M. Zwaan Pediatric acute myeloid leukemia: towards high-quality cure of all patients Haematologica, November 1, 2007; 92(11): 1519 - 1532. [Abstract] [Full Text] [PDF] O. Ottmann, H. Dombret, G. Martinelli, B. Simonsson, F. Guilhot, R. A. Larson, G. Rege-Cambrin, J. Radich, A. Hochhaus, A. M. Apanovitch, et al. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study Blood, October 1, 2007; 110(7): 2309 - 2315. [Abstract] [Full Text] [PDF] H. Pfeifer, B. Wassmann, A. Pavlova, L. Wunderle, J. Oldenburg, A. Binckebanck, T. Lange, A. Hochhaus, S. Wystub, P. Bruck, et al. Kinase domain mutations of BCR-ABL frequently precede imatinib-based therapy and give rise to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) Blood, July 15, 2007; 110(2): 727 - 734. [Abstract] [Full Text] [PDF] O. Spinelli, B. Peruta, M. Tosi, V. Guerini, A. Salvi, M. C. Zanotti, E. Oldani, A. Grassi, T. Intermesoli, C. Mico, et al. Clearance of minimal residual disease after allogeneic stem cell transplantation and the prediction of the clinical outcome of adult patients with high-risk acute lymphoblastic leukemia Haematologica, May 1, 2007; 92(5): 612 - 618. [Abstract] [Full Text] [PDF] P. A. Carpenter, D. S. Snyder, M. E. D. Flowers, J. E. Sanders, T. A. Gooley, P. J. Martin, F. R. Appelbaum, and J. P. Radich Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia Blood, April 1, 2007; 109(7): 2791 - 2793. [Abstract] [Full Text] [PDF] A. de Labarthe, P. Rousselot, F. Huguet-Rigal, E. Delabesse, F. Witz, S. Maury, D. Rea, J.-M. Cayuela, M.-C. Vekemans, O. Reman, et al. Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study Blood, February 15, 2007; 109(4): 1408 - 1413. [Abstract] [Full Text] [PDF] D. A. Thomas Philadelphia Chromosome Positive Acute Lymphocytic Leukemia: A New Era of Challenges Hematology, January 1, 2007; 2007(1): 435 - 443. [Abstract] [Full Text] [PDF] N. Gokbuget and D. Hoelzer Treatment of Adult Acute Lymphoblastic Leukemia Hematology, January 1, 2006; 2006(1): 133 - 141. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020