Efficacy And Plasma Concentration Of Imatinib Mesylate In Patients With Chronic Myeloid Leukemia

Section I THE EFFICACY OF IMATINIB MESYLATE FOR CHRONIC MYELOID LEUKEMIA PATIENTSPurpose:We sought to analyze the clinical efficacy of imatinib mesylate (IM) as a tyrosine kinase inhibitor on Philadelphia chromosome (Ph)-positive or BCR/ABL fusion gene positive chronic myeloid leukemia (CML).Objects and Methods:We reviewed 93 patients admitted to the department of Hematology in Qilu hospital between Febrary 1,2006 and Febrary 28,2010. These 93 CML patients received treatment of IM, including 81 patients in chronic phase(CP),5 patients in accelerated phase(AP) and 7 patients in blast crisis(BC). The dosage of IM is 400mg/day for CP patients,600 mg/day for AP and 800 mg/day for BC patients. Hematological, cytogenetic and molecular effects of IM on the disease process of these patients were evaluated with blood and marrow cells morphology examination, G-band conventional cytogenetics analysis for Ph chromosome and PCR assay for BCR/ABL fusion gene. Dose was adjusted according to the results of blood examination and the patients'tolerance. Results:1. After a median 19-month period of follow-up (range,4-49 months), cumulative complete hematological response(CHR), major cytogenetic response (MCyR), complete cytogenetic response(CCyR) and negative BCR/ABL fusion gene rates were 96.3%(78/81),86.4%(70/83),77.8%(63/83) and 46.9%(38/83) in CML-CP patients. In patients in progressive couse (AP and BC), CHR, MCyR, CCyR and negative BCR/ABL fusion gene rates were 58.3%(7/12),25%(3/12), 25%(3/12) and 8.3%(1/12), respectively. There were apparent differences in the frequencies of hematological, cytogenetic, molecular responses found between these 2 groups.2. No apparent difference in the rates of hematological response was observed between ECP patients and LCP patients. While, MCyR, CCyR and negative BCR/ABL fusion gene rates in ECP patients were higher than those in LCP patients (P<0.01).3. The 4-year OS in the 93 CML patients was 81.6%. The 4-year OS and EFS in the patients in chronic phase were 93.5% and 90%, respectively. All significantly higher than those in patients in progressive couse (AP and BC), whose 4-year OS and EFS were 41.3% and 34.4%, respectively.Conclusions:1. IM significantly improved cytogenetic and molecular response rates, envent-free survival, and overall survival for patients with Ph-positive or BCR/ABL positive CML in chronic phase.2. IM could lead to favorable hematological, cytogenetic and molecular response rates in CML patients in accelerated and blastic phases, while all were lower than those in CML-CP patients.3. Better outcomes of cytogenetic and molecular responses were achieved in ECP patients than those in LCP patients, with treatment of IM. So, IM should be initiated as early as possible so as to get optimal response in CML patients. SectionⅡTROUGH PLASMA CONCENTRATION OF IMATINIB MESYLATE IN PATIENTS WITH CHRONIC MYELOID LEUKEMIAPurposes:We tried to describe the correlation of trough imatinib plasma concentrations (Cmins) with clinical responses and adverse events (AEs) in patients with chronic myeloid leukemia (CML) in chronic phase (CP).Objects and Methods:Using high performance liquid chromatography-tandem mass spectrometry, we assessed trough imatinib plasma concentrations in 23 CML-CP patients.Results:1. The mean trough IM plasma level of 23 CML-CP patients was 1290±546 ng/ML (range,351ng/mL-2180ng/ml).2. Mean trough imatinib plasma levels were significantly higher in the group with complete cytogenetic response (CCyR) at 1 year (1412±440 ng/mL) than in the group without (936±436 ng/mL, P<0.05), and higher in the group with major molecular response (MMR) at 1 year than in the group without MMR (1699±439 ng/mL vs 1072±474 ng/mL, P<0.05).3. There was no statistics significance found among the quartiles of imatinib trough levels in cytogenetic response (P=0.167). While, MMR rates at 1 year differed among the quartiles of imatinib trough levels (P=0.009).4. AE rates were similar among the imatinib quartile categories except neutropenia, thrombocytopenia, anemia, fluid retention, fatigue during the first 3 months treatment period, which were more common at higher imatinib concentrations.Conclusion:The trough level of imatinib showed a significant relationship with its clinical response (CCyR and MMR at 1 year).