Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: Results of a phase II study

Charles L. Sawyers, Andreas Hochhaus, Eric Feldman, John M. Goldman, Carole B. Miller, Oliver G. Ottmann, Charles A. Schiffer, Moshe Talpaz, Francois Guilhot, Michael W N Deininger, Thomas Fischer, Steve G. O'Brien, Richard M. Stone, Carlo B. Gambacorti-Passerini, Nigel H. Russell, Jose J. Reiffers, Thomas C. Shea, Bernard Chapuis, Steven Coutre, Sante TuraEnrica Morra, Richard A. Larson, Alan Saven, Christian Peschel, Alois Gratwohl, Franco Mandelli, Monique Ben-Am, Insa Gathmann, Renaud Capdeville, Ronald L. Paquette, Brian Druker

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)3530-3539
Number of pages10
JournalBlood
Volume99
Issue number10
DOIs
StatePublished - May 15 2002

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Blast Crisis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytogenetics
bcr-abl Fusion Proteins
Imatinib Mesylate
Oncogene Proteins
Proxy
Drug-Related Side Effects and Adverse Reactions
Pharmaceutical Preparations
Refractory materials
Protein-Tyrosine Kinases
Skin
Therapeutics
Safety

ASJC Scopus subject areas

  • Hematology

Cite this

Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis : Results of a phase II study. / Sawyers, Charles L.; Hochhaus, Andreas; Feldman, Eric; Goldman, John M.; Miller, Carole B.; Ottmann, Oliver G.; Schiffer, Charles A.; Talpaz, Moshe; Guilhot, Francois; Deininger, Michael W N; Fischer, Thomas; O'Brien, Steve G.; Stone, Richard M.; Gambacorti-Passerini, Carlo B.; Russell, Nigel H.; Reiffers, Jose J.; Shea, Thomas C.; Chapuis, Bernard; Coutre, Steven; Tura, Sante; Morra, Enrica; Larson, Richard A.; Saven, Alan; Peschel, Christian; Gratwohl, Alois; Mandelli, Franco; Ben-Am, Monique; Gathmann, Insa; Capdeville, Renaud; Paquette, Ronald L.; Druker, Brian.

In: Blood, Vol. 99, No. 10, 15.05.2002, p. 3530-3539.

Research output: Contribution to journalArticle

Sawyers, CL, Hochhaus, A, Feldman, E, Goldman, JM, Miller, CB, Ottmann, OG, Schiffer, CA, Talpaz, M, Guilhot, F, Deininger, MWN, Fischer, T, O'Brien, SG, Stone, RM, Gambacorti-Passerini, CB, Russell, NH, Reiffers, JJ, Shea, TC, Chapuis, B, Coutre, S, Tura, S, Morra, E, Larson, RA, Saven, A, Peschel, C, Gratwohl, A, Mandelli, F, Ben-Am, M, Gathmann, I, Capdeville, R, Paquette, RL & Druker, B 2002, 'Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: Results of a phase II study', Blood, vol. 99, no. 10, pp. 3530-3539. https://doi.org/10.1182/blood.V99.10.3530
Sawyers, Charles L. ; Hochhaus, Andreas ; Feldman, Eric ; Goldman, John M. ; Miller, Carole B. ; Ottmann, Oliver G. ; Schiffer, Charles A. ; Talpaz, Moshe ; Guilhot, Francois ; Deininger, Michael W N ; Fischer, Thomas ; O'Brien, Steve G. ; Stone, Richard M. ; Gambacorti-Passerini, Carlo B. ; Russell, Nigel H. ; Reiffers, Jose J. ; Shea, Thomas C. ; Chapuis, Bernard ; Coutre, Steven ; Tura, Sante ; Morra, Enrica ; Larson, Richard A. ; Saven, Alan ; Peschel, Christian ; Gratwohl, Alois ; Mandelli, Franco ; Ben-Am, Monique ; Gathmann, Insa ; Capdeville, Renaud ; Paquette, Ronald L. ; Druker, Brian. / Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis : Results of a phase II study. In: Blood. 2002 ; Vol. 99, No. 10. pp. 3530-3539.
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AU - Goldman, John M.

AU - Miller, Carole B.

AU - Ottmann, Oliver G.

AU - Schiffer, Charles A.

AU - Talpaz, Moshe

AU - Guilhot, Francois

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AU - Fischer, Thomas

AU - O'Brien, Steve G.

AU - Stone, Richard M.

AU - Gambacorti-Passerini, Carlo B.

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AU - Shea, Thomas C.

AU - Chapuis, Bernard

AU - Coutre, Steven

AU - Tura, Sante

AU - Morra, Enrica

AU - Larson, Richard A.

AU - Saven, Alan

AU - Peschel, Christian

AU - Gratwohl, Alois

AU - Mandelli, Franco

AU - Ben-Am, Monique

AU - Gathmann, Insa

AU - Capdeville, Renaud

AU - Paquette, Ronald L.

AU - Druker, Brian

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