From the Division of Hematology and Internal Medicine, Department of Clinical and Biological Sciences of the University of Turin, Turin, Italy; CEINGE and Department of Biochemistry and Medical Biotechnology, University of Naples Federico II, Naples, Italy; and Institute of Hematology and Medical Oncology "Seragnoli," University of Bologna, Bologna, Italy
Authors' disclosures of potential conflicts of interest are found at the end of this article.
Supported by grants from Associazione Italiana contro le Leucemie and Associazione Italiana per la Ricerca sul Cancro.
Address reprint requests to Giuseppe Saglio, MD, Department of Clinical and Biological Sciences of the University of Turin, San Luigi Hospital, 10043 Orbassano, Torino, Italy; e-mail: giuseppe.saglio{at}unito.it
Overview: Impressive response rates and good tolerability have made imatinib the standard frontline therapy for patients with chronic myeloid leukemia (CML). Although hematologic and cytogenetic parameters are response indicators to monitoring the response during the first treatment phase, given the high rates of complete cytogenetic remission (CCyR) achieved with imatinib therapy, molecular monitoring of BCR-ABL transcript levels by real-time quantitative polymerase chain reaction (RT-PCR) has emerged as the preferred method of assessing the amount of residual disease below the cytogenetic threshold. BCR-ABL transcript levels measured at specific time points during therapy are predictors of durable prolonged progression-free survival and, conversely, of failure and suboptimal responses requiring therapeutic intervention. Recommendations for harmonizing current methodologies for measuring BCR-ABL transcripts for patients with CML have been undertaken; in particular, an ongoing cooperative international program has been designed with the intent of pooling data from individual laboratories that can be reported in a standardized worldwide valid international scale. Rising levels of BCR-ABL transcripts must be a trigger for kinase mutation analysis, the major mechanism of imatinib resistance. The early detection and the characterization of these mutations may allow timely and appropriate treatment interventions to overcome resistance. As in some cases, suboptimal responses and failure to respond to treatment may be a result of low imatinib plasma concentration, the level of which may be relevant to optimizing treatment.
