ABL kinase inhibitor therapy for CML: baseline assessments and response monitoring.
For chronic phase chronic myeloid leukemia (CML) patients treated with imatinib, the essential pre-therapy assessments include bone marrow morphology and cytogenetics as well as a baseline real-time quantitative PCR (RQ-PCR) for BCR-ABL. Baseline assessments of clinical relevance include Sokal and Hasford prognostic scores. Several other baseline assays are likely to be predictive of response, including IC50(imatinib), organic cation transporter-1 (OCT-1) mRNA level, and gene expression profiles, but further confirmation is required. RQ-PCR assays of blood at least every 3 months once patients have commenced imatinib is recommended. This will facilitate early identification of suboptimal responders who may benefit from higher doses of imatinib or alternative therapy, and identify at an early stage patients with acquired resistance. Management of the latter group can be further guided by the findings from cytogenetics and BCR-ABL kinase domain mutation screening. Bone marrow cytogenetics is indicated at least every 6 months until the patient achieves major molecular response. RQ-PCR is only clinically useful if it is conducted under a rigorous quality control regimen so that fluctuations in the BCR-ABL level can be confidently attributed to a biological cause rather than assay variation. To further improve the clinical value of RQ-PCR monitoring, expression of results on an international scale is needed. This will facilitate a more uniform and rational approach to management of suboptimal response and loss of response.
Hughes
Timothy
T
Institute of Medical Veterinary Science, Frome Road, Adelaide 5000, Australia. timothy.hughes@imvs.sa.gov.au
D019468:Disease Management; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
D047428:Protein Kinase Inhibitors; D016315:Proto-Oncogene Proteins c-abl