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Previous Volume 344:1038-1042 April 5, 2001 Number 14 Next

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ABSTRACT

Background BCR-ABL, a constitutively activated tyrosine kinase, is the product of the Philadelphia (Ph) chromosome. This enzyme is present in virtually all cases of chronic myeloid leukemia (CML) throughout the course of the disease, and in 20 percent of cases of acute lymphoblastic leukemia (ALL). On the basis of the substantial activity of the inhibitor in patients in the chronic phase, we evaluated STI571 (formerly known as CGP 57148B), a specific inhibitor of the BCR-ABL tyrosine kinase, in patients who had CML in blast crisis and in patients with Ph-chromosome–positive ALL.

Methods In this dose-escalating pilot study, 58 patients were treated with STI571; 38 patients had myeloid blast crisis and 20 had ALL or lymphoid blast crisis. Treatment was given orally at daily doses ranging from 300 to 1000 mg.

Results Responses occurred in 21 of 38 patients (55 percent) with a myeloid-blast-crisis phenotype; 4 of these 21 patients had a complete hematologic response. Of 20 patients with lymphoid blast crisis or ALL, 14 (70 percent) had a response, including 4 who had complete responses. Seven patients with myeloid blast crisis continue to receive treatment and remain in remission from 101 to 349 days after starting the treatment. All but one patient with lymphoid blast crisis or ALL has relapsed. The most frequent adverse effects were nausea, vomiting, edema, thrombocytopenia, and neutropenia.

Conclusions The BCR-ABL tyrosine kinase inhibitor STI571 is well tolerated and has substantial activity in the blast crises of CML and in Ph-chromosome–positive ALL.

Source Information

From the Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland (B.J.D.); the Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles (C.L.S.); the Departments of Leukemia (H.K.) and Bioimmunotherapy (M.T.), University of Texas M.D. Anderson Cancer Center, Houston; and the Department of Oncology Clinical Research, Novartis Pharmaceuticals, East Hanover, N.J. (D.R.J.), and Basel, Switzerland (S.F.R., J.M.F., R.C.).

Address reprint requests to Dr. Druker at Oregon Health Sciences University, L592, 3181 SW Sam Jackson Park Rd., Portland, OR 97201, or at drukerb{at}ohsu.edu.

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