The translocation (9;22) gives rise to the p190(Bcr-Abl) and p210(Bcr-Abl) 
tyrosine kinase proteins, considered sufficient for leukemic transformation. 
Philadelphia-positive (Ph(+)) acute leukemia patients failing to respond to 
initial induction therapy have a poor prognosis with few effective treatment 
options. Imatinib is an orally administered, potent inhibitor of the Bcr-Abl 
tyrosine kinase. We conducted a clinical trial in 56 patients with relapsed or 
refractory Ph(+) acute lymphoblastic leukemia (ALL; 48 patients) or chronic 
myelogenous leukemia in lymphoid blast crisis (LyBC; 8 patients). Imatinib was 
given once daily at 400 mg or 600 mg. Imatinib induced complete hematologic 
responses (CHRs) and complete marrow responses (marrow-CRs) in 29% of ALL 
patients (CHR, 19%; marrow-CR, 10%), which were sustained for at least 4 weeks 
in 6% of patients. Median estimated time to progression and overall survival for 
ALL patients were 2.2 and 4.9 months, respectively. CHRs were reported for 3 
(38%) of the patients with LyBC (one sustained CHR). Grade 3 or 4 
treatment-related nonhematologic toxicity was reported for 9% of patients; none 
of the patients discontinued therapy because of nonhematologic adverse 
reactions. Grade 4 neutropenia and thrombocytopenia occurred in 54% and 27% of 
patients, respectively. Imatinib therapy resulted in a clinically relevant 
hematologic response rate in relapsed or refractory Ph(+) acute lymphoid 
leukemia patients, but development of resistance and subsequent disease 
progression were rapid. Further studies are warranted to test the effects of 
imatinib in combination with other agents and to define the mechanisms of 
resistance to imatinib.