title: Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study.
abstract: Blast crisis is the most advanced stage of chronic myelogenous leukemia (CML) and is highly refractory to therapy. CML is caused by expression of the chimeric BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Imatinib (Glivec, formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl tyrosine kinase. A total of 260 patients with CML were enrolled in a phase II trial, of whom 229 had a confirmed diagnosis of CML in blast crisis. Patients were treated with imatinib in daily oral doses of 400 mg or 600 mg. Imatinib induced hematologic responses in 52% of patients and sustained hematologic responses lasting at least 4 weeks in 31% of patients, including complete hematologic responses in 8%. For patients with a sustained response, the estimated median response duration was 10 months. Imatinib induced major cytogenetic responses in 16% of patients, with 7% of the responses being complete. Median survival time was 6.9 months. Nonhematologic adverse reactions were frequent but generally mild or moderate. Episodes of severe cytopenia were also frequent and were attributable to the underlying condition and treatment with imatinib. Drug-related adverse events led to discontinuation of therapy in 5% of patients, most often because of cytopenia, skin disorders, or gastrointestinal reactions. These results demonstrate that imatinib has substantial activity and a favorable safety profile when used as a single agent in patients with CML in blast crisis. Additional clinical studies are warranted to explore the efficacy and feasibility of imatinib used in combination with other antileukemic drugs.
authors: Department of Medicine and Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA. csawyers@mednet.ucla.edu
authors: Charles L
authors: CL
authors: Sawyers
authors: Andreas
authors: A
authors: Hochhaus
authors: Eric
authors: E
authors: Feldman
authors: John M
authors: JM
authors: Goldman
authors: Carole B
authors: CB
authors: Miller
authors: Oliver G
authors: OG
authors: Ottmann
authors: Charles A
authors: CA
authors: Schiffer
authors: Moshe
authors: M
authors: Talpaz
authors: Francois
authors: F
authors: Guilhot
authors: Michael W N
authors: MW
authors: Deininger
authors: Thomas
authors: T
authors: Fischer
authors: Steve G
authors: SG
authors: O'Brien
authors: Richard M
authors: RM
authors: Stone
authors: Carlo B
authors: CB
authors: Gambacorti-Passerini
authors: Nigel H
authors: NH
authors: Russell
authors: Jose J
authors: JJ
authors: Reiffers
authors: Thomas C
authors: TC
authors: Shea
authors: Bernard
authors: B
authors: Chapuis
authors: Steven
authors: S
authors: Coutre
authors: Sante
authors: S
authors: Tura
authors: Enrica
authors: E
authors: Morra
authors: Richard A
authors: RA
authors: Larson
authors: Alan
authors: A
authors: Saven
authors: Christian
authors: C
authors: Peschel
authors: Alois
authors: A
authors: Gratwohl
authors: Franco
authors: F
authors: Mandelli
authors: Monique
authors: M
authors: Ben-Am
authors: Insa
authors: I
authors: Gathmann
authors: Renaud
authors: R
authors: Capdeville
authors: Ronald L
authors: RL
authors: Paquette
authors: Brian J
authors: BJ
authors: Druker
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D001752:Blast Crisis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D001772:Blood Cell Count; D020732:Cytogenetic Analysis; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors*; D006801:Humans; D000068877:Imatinib Mesylate; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl