title: The significance of early, major and stable molecular responses in chronic myeloid leukemia in the imatinib era.
abstract: Tyrosine kinase inhibitors (TKI) have dramatically changed the management and the outcome of chronic myeloid leukemia (CML) patients. Imatinib is recognized as gold standard first-line therapy and impressive clinical and cytogenetic responses are obtained in the majority of chronic phase patients treated with this drug. Quantitative polymerase chain reaction (RQ-PCR) tool is used to monitor molecular residual disease, but practical issues are associated to measurement of molecular responses. Several evidences have now proved that molecular responses have prognostic significance: patients who achieve early molecular response are more likely to obtain durable cytogenetic response and to present less rate of disease progression. While some reports indicated that achieving major molecular response (MMR) represents the most important endpoint associated to best outcome, some other reports indicated that achievement of MMR does not improve the greatest clinical benefit brought by complete cytogenetic response. In this review, we discuss on the role of molecular monitoring, the significance of early response and its correlation with outcome, the significance of major and complete molecular response, the emphasized value of a stable molecular response, the early identification of resistance presenting with increased molecular level.
authors.affiliation: Department of Cellular Biotechnology and Hematology, Sapienza University, Rome, Italy. breccia@bce.uniroma1.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.forename: Giuliana
authors.initials: G
authors.lastname: Alimena
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001549:Benzamides; D015415:Biomarkers / Q000378:metabolism*; D004334:Drug Administration Schedule; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate; D007371:Interferon-gamma / Q000008:administration & dosage; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D010879:Piperazines / Q000008:administration & dosage*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D015996:Survival Rate; D014158:Transcription, Genetic / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D015415:Biomarkers; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D007371:Interferon-gamma; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl