Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12227
Title: Prognosis for patients with CML and >10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline.
Authors: Branford, Susan;Yeung, David T;Parker, Wendy T;Roberts, Nicola D;Purins, Leanne;Braley, Jodi A;Altamura, Haley K;Yeoman, Alexandra L;Georgievski, Jasmina;Jamison, Bronte A;Phillis, Stuart;Donaldson, Zoe;Leong, Mary;Fletcher, Linda;Seymour, John F;Grigg, Andrew P;Ross, David M;Hughes, Timothy P
Affiliation: Department of Genetics and Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia; School of Medicine, and School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia; School of Pharmacy and Medical Science, University of South Adelaide, Adelaide, Australia;
Department of Genetics and Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia; School of Medicine, and Department of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia; Australasian Leukaemia and Lymphoma Group, East Melbourne, Australia;
Department of Genetics and Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia; School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia;
Department of Genetics and Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia;
Australasian Leukaemia and Lymphoma Group, East Melbourne, Australia; Department of Haematology, Peter MacCallum Cancer Centre, East Melbourne, Australia; University of Melbourne, Parkville, Australia;
Australasian Leukaemia and Lymphoma Group, East Melbourne, Australia; University of Melbourne, Parkville, Australia; Department of Haematology, Austin Hospital, Melbourne, Australia;
School of Medicine, and Department of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia; Australasian Leukaemia and Lymphoma Group, East Melbourne, Australia; Department of Haematology, Flinders University and Medical Centre, Bedford Park, Australia; and.
School of Medicine, and Department of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia; Australasian Leukaemia and Lymphoma Group, East Melbourne, Australia; Cancer Theme, South Australian Health and Medical Research Institute, Adelaide, Australia.
Issue Date: 23-May-2014
Citation: Blood 2014; 124(4): 511-8
Abstract: In chronic myeloid leukemia (CML) patients, a breakpoint cluster region-Abelson (BCR-ABL1) value >10% at 3 months of therapy is statistically associated with poorer outcome, yet many of these patients still achieve satisfactory outcomes. We investigated 528 first-line imatinib-treated patients to determine whether patients with the poorest outcome can be better discriminated at 3 months. All outcomes were significantly superior for the 410 patients with BCR-ABL1 ≤10% at 3 months (P < .001). However, the poorest outcomes among the 95 evaluable patients with BCR-ABL1 >10% at 3 months were identified by the rate of BCR-ABL1 decline from baseline, assessed by estimating the number of days over which BCR-ABL1 halved. Patients with BCR-ABL1 halving time <76 days (n = 74) had significantly superior outcomes compared with patients whose BCR-ABL1 values did not halve by 76 days (n = 21; 4-year overall survival, 95% vs 58%, P = .0002; progression-free survival, 92% vs 63%, P = .008; failure-free survival, 59% vs 6%, P < .0001; and major molecular response, 54% vs 5%, P = .008). By multivariate analysis, the halving time was an independent predictor of outcome in this poor risk group. Our study highlighted that the rate of BCR-ABL1 decline may be a critical prognostic discriminator of the patients with very poor outcome among those >10% at 3 months. The International Randomized IFN vs STI571 (IRIS) trial was registered at http://www.clinicaltrials.gov as #NCT00006343. The Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) trial was registered at http://www.clinicaltrials.gov as #NCT00124748. The Therapeutic Intensification in DE-novo Leukaemia (TIDEL) I trial was registered at http://www.ANZCTR.org.au as #ACTRN12607000614493. The TIDEL II trial was registered at http://www.ANZCTR.org.au as #ACTRN12607000325404.
Internal ID Number: 24859364
URI: http://ahro.austin.org.au/austinjspui/handle/1/12227
DOI: 10.1182/blood-2014-03-566323
URL: http://www.ncbi.nlm.nih.gov/pubmed/24859364
Type: Journal Article
Subjects: Antineoplastic Agents.therapeutic use
Benzamides.therapeutic use
Female
Follow-Up Studies
Fusion Proteins, bcr-abl.genetics.metabolism
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive.drug therapy.metabolism.mortality
Male
Middle Aged
Piperazines.therapeutic use
Prognosis
Pyrimidines.therapeutic use
Remission Induction
Survival Rate
Time Factors
Appears in Collections:Journal articles

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