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Objective To investigate the mesylate imatinib significance behalf of Nepal (Gleevec, IM) treatment of chronic myelogenous leukemia (CML) patients resistant to ABL kinase domain point mutation in patients with drug-resistant; explore imatinib Nepal plasma concentration detection significance in guiding the treatment of CML. Method 1, using nested RT-PCR poor the imatinib treatment effect of 28 cases and 51 bone marrow samples from different periods of the 10 patients with newly diagnosed chronic phase CML patients ABL kinase domain amplification products were purified, sequenced, and the sequence Homology comparison to determine the presence and type of point mutations. 2, the use of liquid chromatography - tandem mass spectrometry (LC-MS/MS) 153 cases of formal taking imatinib imatinib treatment of CML patients with imatinib imatinib plasma concentrations detected, analysis of blood concentration of patients with general characteristics and efficacy the relationship between the. Results detecting point mutations (31.6%) of 12 patients 1,38 patients were M351T2 cases, Q252H7 cases, E279K2 cases, E255V and E356G each; chronic phase, accelerated phase and blast crisis phase of the mutation rate 17.6% (3/17), 41.7% (5/12) and 44.4% (4/9); mutation rate of hematology and genetics resistant patients were 50% (5/10) and 44.4% ( 8/18), 95% confidence interval, 12.3% -87.7% 19% -69.9%; 12 patients found that point mutations efficacy are poor, after the dosage to 600mg, and were followed up for 3-24 months are disease progression or death in the course of treatment. 2, imatinib imatinib plasma concentration levels correlated with sex (t = 0.9988, P gt; 0.05), age (r = -0.09687), height (r = -0.0663), body weight (r = -0.1881), body surface area (r = -0.1427) and taking IM time no significant correlation (r = 0.0023). 3,111 cases of standard dose imatinib treatment of CML patients in complete cytogenetic response (CCyR), 86 cases in Q1, Q2-3 and Q4 group were 18 cases (67.7%, 18/27), 50 cases (87.7%, 50/57) and 18 patients (67.7%, 18/27) among the three groups, χ2 = 7.04, P lt; 0.05; 86 CCyR patients the level of plasma trough concentrations [(1643.45 ± 594.10) ng / ml] higher than the 25 patients did not receive CCyR plasma trough concentration levels [(830.48 ± 117.35) ng / ml] (P lt; 0.05, t = 6.78); 106 cases of molecular biology assessment of patients, 63 patients were molecular remission (MMR), IM trough plasma concentration level (1671.3 ± 349.38) ng / ml] than not get the MMR IM trough plasma concentration levels in 43 patients (925.49 ± 147.47) ng / ml] (t = 13.202, P lt; 0.05). Conclusion 1, ABL kinase domain point mutation is one of the important reasons for CML treated with imatinib failure. The presence of a high frequency of occurrence of imatinib Nigerian patients with resistant BCR / ABL gene ABL kinase domain point mutation, regular monitoring of the ABL kinase domain point mutations contribute to early intervention measures to improve the treatment level and timing of treatment to avoid the loss of important . 2, accelerated, and blastic phase CML patients with a higher mutation detection rate appear mutation poor prognosis, the observation period should be shortened, timely adjustment of treatment; mutation detection rate in patients with late chronic phase chronic phase patients in the standard should be conducted regularly gene mutation detection and close observation of changes in the patient's condition in order to be able to take early measures to intervene. 3, imatinib the Nepal plasma concentration levels with the general characteristics of the patients' gender, age, height, weight, body surface area has nothing to do. 4 chronic phase CML patients taking 400mg standard dose treatment, Q2-group patients CCyR number of patients was significantly more than the Q1 and Q4 group CCyR patients with IM plasma trough concentrations of water on average higher than CCyR patients Step within a certain range high blood concentration levels help to improve the the CCyR rate, to achieve a better therapeutic effect, but the high concentration of blood levels may adversely affect the treatment of patients. 5, the taking 400mg standard dose treatment of chronic phase CML patients, three groups of molecular remission rate (MMR) no significant difference, but higher than that of the MMR patients with IM plasma trough concentration levels MMR patients, suggesting plasma concentration may be beneficial to patients with MMR, but the optimum concentration range has yet to be further clear.
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