Rabbit Anti-Human ABL1 (Phospho-Thr735) polyclonal antibody

Chronic myeloid leukemia (CML) is a hematological malignancy that constitutes 15-20% of leukemias in adults and is in the rare diseases group. In CML, genetic diagnosis involves a long process, which should be carried out in collaboration between the sub-disciplines of medical genetics, and that the clinical information of the patient should be taken into consideration during follow-up. While cytogenetics, fluorescent in situ hybridization and real-time PCR methods are used in diagnosis and follow-up; Sanger sequencing and next generation sequencing methods are especially used in determining prognosis and treatment resistance. It is thought that the current genetic diagnostic algorithms will be revised and the treatments will be made more effective with future exom, genome and transcriptom studies.

Background: Imatinib is one of the first-line therapies for chronic myeloid leukemia. Achieving a major molecular response early in treatment, as indicated by a BCR-ABL1 major international scale result of <= 0.1% within 6 months, is associated with better patient outcomes and is statistically associated with a trough imatinib concentration of approximately 1000 ng/mL. Adherence to therapy, drug resistance, drug-drug interactions, and pharmacokinetic/pharmacodynamic factors may hinder attaining this target. Therapeutic drug monitoring of imatinib is not currently standard-of-care, but may help to evaluate adherence and optimize treatment of patients with chronic myeloid leukemia. This study aimed to evaluate imatinib concentrations in real-world patient plasma samples to identify the proportion of imatinib-treated patients who achieved the therapeutic target of 1000 ng/mL. Methods: This was a retrospective, observational study that measured imatinib in residual plasma samples used for BCR-ABL1 tests (n = 1022) and analyzed clinician-ordered imatinib tests for therapeutic drug monitoring (n = 116). Imatinib was measured by competitive immunoassay. The frequency of imatinib concentrations achieving the therapeutic target was determined and correlated with BCR-ABL1 major international scale, age, and sex. Results: Seventy-two percent of patients tested for BCR-ABL1 may not have been prescribed or were not adherent to imatinib therapy. In the 29% of patients who did not achieve major molecular response, but had quantifiable imatinib concentrations, the therapeutic concentration was not met. For clinician-ordered imatinib tests, 45% of samples did not exceed the therapeutic target and 4% had potentially toxic plasma concentrations (>3000 ng/mL). Conclusions: Therapeutic drug monitoring for imatinib may assist clinicians in the identification of patients who may not be adherent to therapy, display variable pharmacokinetics or pharmacodynamics, or may be experiencing toxicity or treatment failure.