In a recent report (21) it was also suggested (a) that in late-CP and AP patients treated with Imatinib, mutations can be detected by direct sequencing before clinical evidence of resistance, thus predicting the subsequent course of the disease; (b) that mutations in the nucleotide-binding loop of the kinase region (P-loop) are associated with a particularly poor prognosis; and (c) that patients with longer duration of CML before initiation of Imatinib therapy and patients who fail to achieve a major cytogenetic response (MCgR) in the first 6 months of therapy are at high risk of developing mutations and resistance and should be regularly monitored.
Cytogenetic resistance was defined according to the following criteria: (a) patients failed to obtain at least a MCgR within the first 12 months of therapy, or (b) patients transiently obtained a MCgR or even a complete cytogenetic response within the first 12 months but subsequently lost it.
ABL mutational analysis was done at the 12th month of therapy for those patients who, despite not reaching a stable MCgR or complete cytogenetic response, showed hematologic response and completed the first year of therapy (n = 19).
Because point mutations affecting critical sites within the ABL kinase domain seem to be one of the most frequent mechanisms of resistance (with frequencies ranging from 26% to 90% depending on the phase of the disease) (4-11), mutational screening of patients undergoing Imatinib treatment, especially those considered at higher risk of developing resistance--i.e., patients with longer duration of CML before initiation of Imatinib therapy and patients who fail to achieve a MCgR in the first 6 months of therapy (21)--should routinely be performed to help decision-making on dose escalation or alternative treatment options.
How long are they going to kid the Celtic fans on?" Robert McGregor, Rugby, said: "I'm a big Rangers McGr
fan and have to laugh at Celtic going for McFadden.