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Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: Results of a phase 2 study

Lookup NU author(s): Dr Anne Lennard

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Abstract

Chronic myelogenous leukemia (CML) is caused by expression of the BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Patients with CML in accelerated phase have rapidly progressive disease and are characteristically unresponsive to existing therapies. Imatinib (formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl kinase. A total of 235 CML patients were enrolled in this study, of whom 181 had a confirmed diagnosis of accelerated phase. Patients were treated with imatinib at 400 or 600 mg/d and were evaluated for hematologic and cytogenetic response, time to progression, survival, and toxicity. Imatinib induced hematologic response in 82% of patients and sustained hematologic responses lasting at least 4 weeks in 69% (complete in 34%). The rate of major cytogenetic response was 24% (complete in 17%). Estimated 12-month progression-free and overall survival rates were 59% and 74%, respectively. Nonhematologic toxicity was usually mild or moderate, and hematologic toxicity was manageable. In comparison to 400 mg, imatinib doses of 600 mg/d led to more cytogenetic responses (28% compared to 16%), longer duration of response (79% compared to 57% at 12 months), time to disease progression (67% compared to 44% at 12 months), and overall survival (78% compared to 65% at 12 months), with no clinically relevant increase in toxicity. Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase. A daily dose of 600 mg is more effective than 400 mg, with similar toxicity. © 2002 by The American Society of Hematology.


Publication metadata

Author(s): Talpaz, M., Silver, R., Druker, B., Goldman, J., Gambacorti-Passerini, C., Guilhot, F., Schiffer, C., Fischer, T., Deininger, M., Lennard, A.L., Hochhaus, A., Ottmann, O., Gratwohl, A., Baccarani, M., Stone, R, Tura, S., Mahon, F., Fernandes-Reese, S., Gathmann, I, Capdeville, R., Kantarjian, H., Sawyers, C.

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2002

Volume: 99

Issue: 6

Pages: 1928-1937

Print publication date: 15/03/2002

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

URL: http://dx.doi.org/10.1182/blood.V99.6.1928

DOI: 10.1182/blood.V99.6.1928

PubMed id: 11877262


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