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. 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. 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. 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.
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 . 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 . 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 . 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 .
What tyrosine kinase, involved in a Philadelphia- chromosome positive chronic myelogenous leukemia, is the target of Imatinib (Gleevec)?
What tyrosine kinase , involved in a Philadelphia- chromosome positive chronic myelogenous leukemia , is the target of Imatinib ( Gleevec ) ?
BCR-ABL
BCR-ABL