Molecular abnormalities caused by the hybrid Bcr-Abl gene are causally 
associated with the development and progression of Philadelphia 
chromosome-positive (Ph(+)) chronic myelogenous leukemia (CML). Imatinib 
mesylate (STI571), a specific Bcr-Abl tyrosine-kinase signal-transduction 
inhibitor, has shown encouraging activity in phase I and II studies of CML. 
Here, we describe the use of imatinib mesylate to treat 75 patients in 
blast-phase CML (median age, 53 years; 65 with nonlymphoid and 10 with lymphoid 
blasts), and compare the results with those of a historical control group 
treated with standard cytarabine-based therapy. Imatinib mesylate was given as 
oral doses at 300 to 1000 mg per day and was the first salvage therapy for 47 
patients. The objective response rate was 52% (39 of 75 patients: 16 had 
complete and 3 had partial hematologic response; 12 had hematologic improvement; 
7 returned to second chronic phase; and 1 had a complete response in 
extramedullary blastic disease). Response rates were not different between 
nonlymphoid and lymphoid groups. The cytogenetic response rate was 16% (12 
patients: 5 complete, 3 partial [Ph(+) below 35%], and 4 minor [Ph(+), 34% to 
90%]). The estimated median overall survival was 6.5 months; the estimated 
1-year survival was 22%. Response to therapy (landmark analysis at 8 weeks) was 
associated with survival prolongation. Compared with standard cytarabine 
combinations, imatinib mesylate therapy was less toxic and produced a higher 
response rate (55% versus 29%, P =.001), longer median survival (7 versus 4 
months, P =.04), and lower 4-week induction mortality (4% versus 15%, P =.07). 
Imatinib mesylate is currently being tested in combination with other drugs to 
improve the prognosis for blast-phase CML.