ABL kinase domain mutations in patients with chronic myeloid leukemia in Jordan.

Mutations of the BCR-ABL tyrosine kinase domain constitute a major cause of resistance to tyrosine kinase inhibitors in patients with chronic myelogenous leukemia (CML). In this study, we analyzed peripheral blood samples from 185 Jordanian CML patients for ABL mutations, who were on imatinib for a minimum of 6 months regardless of their disease status and over a period of 5 years. Mutations were detected by nested RT-polymerase chain reaction, followed by direct sequencing of the ABL kinase domain. Twelve different point mutations were detected 25 times in 21 patients. The resultant mutations were as follows: four patients have T315I, three of each of the following: L248V, F317L, and G250E, two of each of the following: H396R, M244V, and T277A, and one of each of the following: F311I, M318T, Q252H, F359A, F359I, and Y326H. After patient follow-up, the mutation had disappeared in 12 patients; 3 patients died; 3 patients were not retested; and 3 patients had persistent mutation. The finding of our study is in line with what has been described in the literature. Detecting ABL mutations in chronic phase may lead to positive outcome by modifying treatment.

Determination of imatinib plasma levels in patients with chronic myeloid leukemia by high performance liquid chromatography-ultraviolet detection and liquid chromatography-tandem mass spectrometry: methods' comparison.

The aims of this study were to validate and compare HPLC and LCMSMS analytical methods and their applicability for the quantitation of imatinib in human plasma. A total of 50 patients with chronic myeloid leukemia (CML) in chronic phase (CP) receiving 400 mg/day imatinib were enrolled in the study. Drug levels were determined by HPLC-UV and LCMSMS. HPLC intra-day accuracy ranged from 100.51 to 103.19%. LCMSMS accuracy ranged from 89.72 to 106.29%. The correlation coefficient between both methods was r(2)=0.96. HPLC can be used for imatinib levels' determinations in patients accurately and precisely.

Relationship of serum imatinib trough level and response in CML patients: long term follow-up.

One hundred and three patients with Philadelphia chromosome or BCR-ABL positive chronic myeloid leukemia (CML) in chronic phase who were on oral imatinib were included in this study. The study aimed to assess the relationship between imatinib trough serum levels and clinical outcome (as determined by molecular response) in Jordanian CML patients who have been on imatinib therapy for at least 12 months. The mean trough imatinib serum level in the group with complete molecular response (CMR) was 2891±856 ng/ml, the group with major molecular response (MMR) was 2337±434 ng/ml, the group with complete cytogenetic response (CCyR) was 1817±563 ng/ml, and the group without CCyR was 1723±673 ng/ml. A receiver operating characteristic (ROC) curve was constructed after dividing patient sample into two groups, those with MMR or better and those without MMR, in order to estimate a threshold for imatinib level that correlates with a favorable response (the former group), and analysis yielded a value of 2158 ng/ml.