title: Definition and treatment of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia.
abstract: Resistance to tyrosine kinase inhibitors (TKIs) has many facets. The causes of resistance include low patient compliance, low plasma or intracellular drug concentration, BCR-ABL1 mutations, and clonal chromosome abnormalities in Ph+ cells, but in at least 50% of patients the causes are currently unknown. Primary resistance occurs when a predefined response level is not achieved within a prespecified period of time. Not achieving a complete hematologic response (CHR) within 3 months, not achieving a partial cytogenetic response and/or a BCR-ABL1 transcripts level ≤10% (international standard) within 6 months, and not achieving a complete cytogenetic response (CCyR) and/or a BCR-ABL1 transcripts level <1% within 12 months, define primary resistance. Secondary resistance is defined by a loss of CHR, or CCyR, or major molecular response. Resistance to imatinib calls without exceptions for a second-generation TKI. In case of resistance to two TKIs, an allogeneic stem cell transplantation should be considered.
authors.affiliation: Department of Hematology and Oncology "L. and A. Seràgnoli", Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Fausto
authors.initials: F
authors.lastname: Castagnetti
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gugliotta
authors.forename: Francesca
authors.initials: F
authors.lastname: Palandri
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
mesh_terms: D019008:Drug Resistance, Neoplasm; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D047428:Protein Kinase Inhibitors
keywords: BCR-ABL1; Philadelphia (chromosome); chronic myeloid leukemia; imatinib; tyrosine kinase inhibitors