Document Detail

Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase.
MedLine Citation:
PMID:  14523461     Owner:  NLM     Status:  MEDLINE    
We analyzed molecular responses in 55 newly diagnosed chronic-phase chronic myeloid leukemia (CML) patients enrolled in a phase 3 study (the IRIS trial) comparing imatinib to interferon-alfa plus cytarabine (IFN+AraC). BCR-ABL/BCR% levels were measured by real-time quantitative RT-PCR and were significantly lower for the imatinib-treated patients at all time points up to 18 months, P<0.0001. The median levels for imatinib-treated patients continued to decrease and had not reached a plateau by 24 months. A total of 24 IFN+AraC-treated patients crossed over to imatinib. Once imatinib commenced, the median BCR-ABL/BCR% levels in these patients were not significantly different to those on first-line imatinib for the equivalent number of months. The incidence of progression in imatinib-treated patients, defined by hematologic, cytogenetic or quantitative PCR criteria, was significantly higher in the patients who failed to achieve a 1 log reduction by 3 months or a 2 log reduction by 6 months, P=0.002. A total of 49 patients were screened for BCR-ABL kinase domain mutations. Mutations were detected in two imatinib-treated patients who crossed over from IFN+AraC and both lost their imatinib response. In conclusion, first-line imatinib-treated patients had profound reductions in BCR-ABL/BCR%, which significantly exceeded those of IFN+AraC-treated patients and early measurements were predictive of subsequent response.
S Branford; Z Rudzki; A Harper; A Grigg; K Taylor; S Durrant; C Arthur; P Browett; A P Schwarer; D Ma; J F Seymour; K Bradstock; D Joske; K Lynch; I Gathmann; T P Hughes
Publication Detail:
Type:  Clinical Trial; Clinical Trial, Phase III; Comparative Study; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Leukemia     Volume:  17     ISSN:  0887-6924     ISO Abbreviation:  Leukemia     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-12-12     Completed Date:  2004-01-23     Revised Date:  2013-03-04    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  England    
Other Details:
Languages:  eng     Pagination:  2401-9     Citation Subset:  IM    
Institute of Medical and Veterinary Science, Adelaide, South Australia.
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MeSH Terms
Antimetabolites, Antineoplastic / administration & dosage*
Antineoplastic Agents / administration & dosage*
Bone Marrow / metabolism
Cross-Over Studies
Cytarabine / administration & dosage*
DNA Mutational Analysis
Fusion Proteins, bcr-abl / blood,  chemistry,  genetics
Interferon-alpha / administration & dosage*
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis,  drug therapy*,  genetics
Phosphotransferases / chemistry,  genetics
Piperazines / administration & dosage*
Protein Structure, Tertiary
Pyrimidines / administration & dosage*
Treatment Outcome
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/Antineoplastic Agents; 0/Fusion Proteins, bcr-abl; 0/Interferon-alpha; 0/Piperazines; 0/Pyrimidines; 147-94-4/Cytarabine; BKJ8M8G5HI/imatinib; EC 2.7.-/Phosphotransferases

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