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Prepublished online as a Blood First Edition Paper on May 15, 2003; DOI 10.1182/blood-2002-09-2763.
Submitted September 16, 2002
Accepted April 30, 2003
Imatinib improves but may not fully reverse the poor prognosis of CML patients with derivative chromosome 9 deletions
Brian J P Huntly, Francois Guilhot, Alistair G Reid, George Vassiliou, Evelin Hennig, Christina Franke, Jennie Byrne, Andre Brizard, Dietger Niederwieser, Julie Freeman-Edward, Gavin Cuthbert, Nick Bown, Richard E Clark, Elizabeth P Nacheva, Anthony R Green, and Michael W N Deininger*
Department of Haematology, University of Cambridge, Cambridge, United Kingdom
Department of Haematology, CHU, Poitiers, France
Department of Haematology, City Hospital, Nottingham, United Kingdom
Department of Haematology, University Hospital, Leipzig, Germany; Cytogenetics Unit, Institute of Human Genetics, University of Newcastle, Newcastle upon Tyne, United Kingdom
Department of Leukemia/BMT, Oregon Health and Science University, Portland, OR, USA
Department of Hematology, University of Liverpool, Liverpool, United Kingdom
* Corresponding author; email: deininge{at}ohsu.edu.
Deletions of the derivative chromosome 9 occur in a subset of patients with Philadelphia-positive CML and are associated with a poor prognosis on standard drug therapy. However, it is currently unknown if the presence of deletions influences the response to imatinib, an Abl specific tyrosine kinase inhibitor which has recently shown excellent hematological and cytogenetic responses in CML patients. We therefore compared hematological and cytogenetic responses to imatinib in 397 CML patients, and survival and progression in 354 of these patients according to deletion status and disease phase. We found no difference in survival between patients with and without deletions, contrasting with previous reports in cohorts with a lower proportion of patients treated with imatinib. However, the time to disease progression on imatinib treatment was significantly shorter for patients with deletions, both in chronic phase (p=0.02) and advanced phases (p=0.02). Moreover, both in chronic phase and more advanced phases of CML, hematological and cytogenetic responses were uniformly lower in patients with deletions, with significant differences seen for hematological response (p=0.04), and major cytogenetic response (p=0.008) in chronic phase, and for hematological response in advanced phases (p=0.007) of CML. This suggests that differences in survival may become apparent with longer follow-up.
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