title: Imatinib Intolerance Is Associated With Blastic Phase Development in Philadelphia Chromosome-Positive Chronic Myeloid Leukemia.
abstract: Over the past years, the survival of patients with Philadelphia-positive chronic myeloid leukemia (CML Ph(+)) has increased as a result of therapy with tyrosin kinase inhibitors (TKIs). Intolerance to TKIs has been described in approximately 20% of patients receiving treatment. We studied the incidence of imatinib intolerance in patients with CML Ph(+) and their outcome in our CML reference site, as there is no information about the evolution of patients intolerant to TKIs.
  
  
  
  A group of 86 patients with CML Ph(+) receiving imatinib monotherapy who abandoned treatment were the basis for this study. We present the trends of their disease evolution.
  
  
  
  The median of age at diagnosis was 42 years. Within a year, 19 (22%) of 86 patients developed imatinib intolerance, all of them with grade III or IV disease that required imatinib dose reduction or discontinuation. Of these patients, 16 (84%) of 19 developed transformation to blastic phase. The cumulative incidences of blastic phase development were 47% in the nonintolerant group and 84% in the intolerant group. There was a relative risk for those with imatinib intolerance to develop blastic phase of 1.78 (95% confidence interval, 1.28 to 2.42) (P < .05).
  
  
  
  Most imatinib-intolerant patients develop blastic phase transformation, with a poor survival of 3 to 6 months; no effective rescue treatment is available. Future research should to determine whether the origin of this evolution is really due to the intolerance itself or whether it is due to a more aggressive form of the disease, perhaps related to genetic transformation.
authors: Resident of Internal Medicine, Mexican Faculty of Medicine, La Salle University, Hospital Angeles del Pedregal, Mexico City, Mexico.
authors: Jorge Luis
authors: JL
authors: Ángeles-Velázquez
authors: Head of the Department of Hematology, Hospital Angeles del Pedregal, Mexico City, Mexico. Electronic address: rafahurtado@prodigy.net.mx.
authors: Rafael
authors: R
authors: Hurtado-Monroy
authors: Department of Hematology, Hospital Angeles del Pedregal, Mexico City, Mexico.
authors: Pablo
authors: P
authors: Vargas-Viveros
authors: Department of Hematology, Hospital Angeles del Pedregal, Mexico City, Mexico.
authors: Silvia
authors: S
authors: Carrillo-Muñoz
authors: Department of Hematology, Hospital Angeles del Pedregal, Mexico City, Mexico.
authors: Myrna
authors: M
authors: Candelaria-Hernández
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage / Q000009:adverse effects*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D028761:Withholding Treatment; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate
keywords: Adverse events; Chronic myeloid leukemia; Survival; Toxicity; Tyrosine kinase inhibitors