SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-02-0360. This Article 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 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 Social Bookmarking                   What's this? Submitted February 4, 2002 Accepted August 1, 2002 Early minimal residual disease (MRD) analysis during treatment of Philadelphia chromosome/Bcr-Bbl positive acute lymphoblastic leukemia (Ph+ALL) with the Abl-tyrosine kinase inhibitor STI571 (Glivec) Urban J Scheuring*, Heike Pfeifer, Barbara Wassmann, Patrick Brueck, Johannes Atta, Eduard K Petershofen, Brigitte Gehrke, Harald Gschaidmeier, Dieter Hoelzer, and Oliver G Ottmann Department of Hematology and Oncology, J. W. Goethe University Hospital, Frankfurt, Germany Red Cross Blood Donation Service, Oldenburg, Germany Novartis Pharma AG, Nuernberg, Germany * Corresponding author; email: scheuring{at}em.uni-frankfurt.de. The Abl kinase inhibitor STI571 (Imatinib or Glivec) has significant and rapid antileukemic activity in Ph+ALL but 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 II trials of STI571 were analyzed by quantitative PCR. STI571 induced a complete hematologic response (CHR) or 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 to baseline, the median Bcr-Abl/GAPDH ratios decreased significantly in PB by 2.65 , 2.64 and 3.11 log steps after 2, 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 versus 39 days). Low Bcr-Abl/GAPDH ratios <10-4 in PB and <10-2 in BM after 2 weeks were significantly associated with good responses after 4 weeks. Moreover, Bcr-Abl levels (<10-2) in BM of good responders after 4 weeks discriminated between two groups of patients with significantly different median time to progression (139 versus 22 days). The data show that Bcr-Abl levels in PB and BM after 2 weeks of STI571 treatment and in BM after 4 weeks have predictive relevance and may guide the application of additional therapies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Riva, M. Luppi, P. Barozzi, C. Quadrelli, S. Basso, D. Vallerini, E. Zanetti, M. Morselli, F. Forghieri, M. Maccaferri, et al. Emergence of BCR-ABL-specific cytotoxic T cells in the bone marrow of patients with Ph+ acute lymphoblastic leukemia during long-term imatinib mesylate treatment Blood, February 25, 2010; 115(8): 1512 - 1518. [Abstract] [Full Text] [PDF] 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. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia Blood, February 1, 2006; 107(3): 1116 - 1123. [Abstract] [Full Text] [PDF] T. Haferlach, A. Kohlmann, S. Schnittger, M. Dugas, W. Hiddemann, W. Kern, and C. Schoch Global approach to the diagnosis of leukemia using gene expression profiling Blood, August 15, 2005; 106(4): 1189 - 1198. [Abstract] [Full Text] [PDF] B. Wassmann, H. Pfeifer, M. Stadler, M. Bornhauser, G. Bug, U. J. Scheuring, P. Bruck, M. Stelljes, R. Schwerdtfeger, N. Basara, et al. Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) Blood, July 15, 2005; 106(2): 458 - 463. [Abstract] [Full Text] [PDF] S. Lee, Y.-J. Kim, C.-K. Min, H.-J. Kim, K.-S. Eom, D.-W. Kim, J.-W. Lee, W.-S. Min, and C.-C. Kim The effect of first-line imatinib interim therapy on the outcome of allogeneic stem cell transplantation in adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia Blood, May 1, 2005; 105(9): 3449 - 3457. [Abstract] [Full Text] [PDF] D. A. Thomas, S. Faderl, J. Cortes, S. O'Brien, F. J. Giles, S. M. Kornblau, G. Garcia-Manero, M. J. Keating, M. Andreeff, S. Jeha, et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate Blood, June 15, 2004; 103(12): 4396 - 4407. [Abstract] [Full Text] [PDF] P. Bolufer, D. Colomer, M. T. Gomez, J. Martinez, S. M. Gonzalez, M. Gonzalez, J. Nomdedeu, B. Bellosillo, E. Barragan, F. Lo-Coco, et al. Quantitative Assessment of PML-RARa and BCR-ABL by Two Real-Time PCR Instruments: Multiinstitutional Laboratory Trial Clin. Chem., June 1, 2004; 50(6): 1088 - 1092. [Full Text] [PDF] B. Wassmann, H. Pfeifer, U. J. Scheuring, A. Binckebanck, N. Gokbuget, J. Atta, P. Bruck, H. Rieder, C. Schoch, L. Leimer, et al. Early prediction of response in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) treated with imatinib Blood, February 15, 2004; 103(4): 1495 - 1498. [Abstract] [Full Text] [PDF] S. Lee, D.-W. Kim, Y.-J. Kim, N.-G. Chung, Y.-L. Kim, J.-Y. Hwang, and C.-C. Kim Minimal residual disease-based role of imatinib as a first-line interim therapy prior to allogeneic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia Blood, October 15, 2003; 102(8): 3068 - 3070. [Abstract] [Full Text] [PDF] J. Kuroda, S. Kimura, H. Segawa, Y. Kobayashi, T. Yoshikawa, Y. Urasaki, T. Ueda, F. Enjo, H. Tokuda, O. G. Ottmann, et al. The third-generation bisphosphonate zoledronate synergistically augments the anti-Ph+ leukemia activity of imatinib mesylate Blood, September 15, 2003; 102(6): 2229 - 2235. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020