Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia withthe philadelphia chromosome.

Background: BCR-ABL, a constitutively activated tyrosine kinase, is the pro duct of the Philadelphia (Ph) chromosome. This enzyme is present in virtual ly 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 t he chronic phase, we evaluated STI571 (formerly known as CGP 57148B), a spe cific 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 bl ast crisis. Treatment was given orally at daily doses ranging from 300 to 1 000 mg. Results: Responses occurred in 21 of 38 patients (55 percent) with a myeloi d-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 wi th myeloid blast crisis continue to receive treatment and remain in remissi on from 101 to 349 days after starting the treatment. All but one patient w ith lymphoid blast crisis or ALL has relapsed. The most frequent adverse ef fects 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-chromoso me-positive ALL. (N Engl J Med 2001;344:1038-42.) Copyright (C) 2001 Massac husetts Medical Society.