PURPOSE: Imatinib mesylate is a tyrosine kinase inhibitor with high affinity for 
the BCR-ABL fusion protein expressed by the hematopoietic cells in chronic 
myelogenous leukemia (CML). Some patients with chronic-phase or 
accelerated-phase CML either relapse after an initial response or are refractory 
to imatinib, prompting us to evaluate the efficacy of dose increase in such 
patients.
EXPERIMENTAL DESIGN: Twelve chronic-phase patients initially receiving 400 
mg/day and 4 patients with accelerated phase initially receiving either 400 
mg/day (two patients) or 600 mg/day (two patients) had their dose increased (14 
to 800 mg/day and 2 to 600 mg/day) because of progressive disease (usually 
clonal evolution) or inadequate cytogenetic response after at least 1 year of 
therapy.
RESULTS: Six patients had major cytogenetic responses after dose increase (3 
complete and 3 partial). Two others had minor cytogenetic responses. Two 
patients with clonal evolution transiently lost the additional clonal 
aberrations. Almost all of the responses occurred within 6 months, and were 
typically 3-6 months in duration. However, 3 patients have continuing major 
cytogenetic responses of >18 months duration. Dose increase was well tolerated, 
with thrombocytopenia, mild leukopenia, and exacerbation of prior edema being 
the most common adverse events.
CONCLUSIONS: Although increasing the dose of imatinib can benefit a subgroup of 
patients with CML with either an inadequate cytogenetic response or disease 
progression, our results suggest the majority will not have a sustained 
meaningful response, and that other options, such as allogeneic stem cell 
transplant or investigational therapies, also need to be considered at the time 
of dose increase.