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Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS)

Lookup NU author(s): Dr Michelle Muller, Professor Stephen O'Brien


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This study examines the prognostic significance of early molecular response using an expanded dataset in chronic myeloid leukemia patients enrolled in the International Randomized Study of Interferon and STI571 (IRIS). Serial molecular studies demonstrate decreases in BCR-ABL transcripts over time. Analyses of event-free survival (EFS) and time to progression to accelerated phase/blast crisis (AP/BC) at 7 years were based on molecular responses using the international scale (IS) at 6-, 12-, and 18-month landmarks. Patients with BCR-ABL transcripts > 10% at 6 months and > 1% at 12 months had inferior EFS and higher rate of progression to AP/BC compared with all other molecular response groups. Conversely, patients who achieved major molecular response [MMR: BCR-ABL (IS) <= 0.1%] by 18 months enjoyed remarkably durable responses, with no progression to AP/BC and 95% EFS at 7 years. The probability of loss of complete cytogenetic response by 7 years was only 3% for patients in MMR at 18 months versus 26% for patients with complete cytogenetic response but not MMR (P < .001). This study shows a strong association between the degree to which BCR-ABL transcript numbers are reduced by therapy and long-term clinical outcome, supporting the use of time-dependent molecular measures to determine optimal response to therapy. This study is registered at as NCT00006343. (Blood. 2010;116(19):3758-3765)

Publication metadata

Author(s): O'Brien SG; Muller MC; Hughes TP; Hochhaus A; Branford S; Kaeda JS; Foroni L; Druker BJ; Guilhot F; Larson RA; Rudoltz MS; Mone M; Wehrle E; Modur V; Goldman JM; Radich JP

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2010

Volume: 116

Issue: 19

Pages: 3758-3765

Print publication date: 02/08/2010

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology


DOI: 10.1182/blood-2010-03-273979


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Funder referenceFunder name
Bristol-Myers Squibb
National Health and Medical Research Council of Australia
Novartis Pharmaceuticals
DJCLS H03/01Deutsche Jose Carreras-Leukamiestiftung
CA 18 029NIH/NCI