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Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-02-0360. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-02-0360v1 101/1/85    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Scheuring, U. J. Articles by Ottmann, O. G. Search for Related Content PubMed PubMed Citation Articles by Scheuring, U. J. Articles by Ottmann, O. G. Related Collections Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 January 2003, Vol. 101, No. 1, pp. 85-90 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Early minimal residual disease (MRD) analysis during treatment of Philadelphia chromosome/Bcr-Abl-positive acute lymphoblastic leukemia with the Abl-tyrosine kinase inhibitor imatinib (STI571) Urban J. Scheuring, Heike Pfeifer, Barbara Wassmann, Patrick Brück, Johannes Atta, Eduard K. Petershofen, Brigitte Gehrke, Harald Gschaidmeier, Dieter Hoelzer, and Oliver G. Ottmann From the Medizinische Klinik III, Abteilung für Hämatologie und Onkologie of the Johann Wolfgang Goethe-Universität, Frankfurt, Germany; Red Cross Blood Donation Service, Oldenburg, Germany; and Novartis Pharma AG, Nürnberg, Germany. The Abl kinase inhibitor imatinib mesylate (STI571) has significant and rapid antileukemic activity in Philadelphia chromosome/Bcr-Abl-positive acute lymphoblastic leukemia (Ph+ ALL) but such activity is usually of short duration except for a small proportion of patients. To determine the prognostic significance of early Bcr-Abl levels and changes in peripheral blood (PB) and bone marrow (BM), serial samples of 56 patients with relapsed or refractory Ph+ ALL treated in phase 2 trials of imatinib were analyzed by quantitative polymerase chain reaction (PCR). Imatinib induced a complete hematologic response (CHR) or complete marrow response (marrow-CR) in 40 patients (good responders) and a partial (n = 2) or no (n = 14) remission in the remaining patients (poor responders). Compared with baseline, the median Bcr-Abl/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ratios decreased significantly in PB by 2.65, 2.64, and 3.11 log steps after 2 weeks, 4 weeks, and at the time of best response, respectively. In BM, the decline of median Bcr-Abl/GAPDH was 0.75, 1.37, and 2.78 logs, respectively. Thus, Bcr-Abl levels decreased more rapidly in PB than in BM (median time to best level 31 vs 39 days). Low Bcr-Abl/GAPDH ratios below 104 in PB and below 102 in BM after 2 weeks were significantly associated with good responses after 4 weeks. Moreover, Bcr-Abl levels (< 102) in BM of good responders after 4 weeks discriminated between 2 groups of patients with significantly different median time to progression (139 vs 22 days). The data show that Bcr-Abl levels in PB and BM after 2 weeks of imatinib treatment and in BM after 4 weeks have predictive relevance and may guide the application of additional therapies. © 2003 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: B. Wassmann, H. Pfeifer, N. Goekbuget, D. W. Beelen, J. Beck, M. Stelljes, M. Bornhauser, A. Reichle, J. Perz, R. Haas, et al. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL) Blood, September 1, 2006; 108(5): 1469 - 1477. [Abstract] [Full Text] [PDF] M. Bruggemann, T. Raff, T. Flohr, N. Gokbuget, M. Nakao, J. Droese, S. Luschen, C. Pott, M. Ritgen, U. Scheuring, et al. 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