title: Discontinuation of tyrosine kinase inhibitors and new approaches to target leukemic stem cells: treatment-free remission as a new goal in chronic myeloid leukemia.
abstract: Only a small fraction of chronic phase chronic myeloid leukemia patients (CP-CML) achieves a very deep reduction of residual disease with imatinib. Second-generation tyrosine kinase inhibitors administered as front-line therapy for CP-CML have improved the rates and degree of deeper molecular responses. Owing to this improvement, new standardized definition of complete molecular remission has been provided, which allowed plan of prospective strategies to definitively discontinue therapy in the long-term. In this review, we report the results of several published discontinuation studies and critically discuss the new approaches and tools to monitor residual disease during treatment and new strategies to target leukemic stem cells to reach a potential "operational" cure and persistent long-term leukemia-free survival.
authors: Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy. Electronic address: breccia@bce.uniroma1.it.
authors: Massimo
authors: M
authors: Breccia
authors: Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
authors: Giuliana
authors: G
authors: Alimena
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D012074:Remission Induction
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases
keywords: Chronic myeloid leukemia; Discontinuation; Relapse