Long-term results of high-dose imatinib in children and adolescents with chronic myeloid leukaemia in chronic phase: the Italian experience

Br J Haematol. 2015 Aug;170(3):398-407. doi: 10.1111/bjh.13453. Epub 2015 Apr 20.

Abstract

Imatinib mesylate (IM) is used for the management of childhood chronic myeloid leukaemia (CML). The most effective dosage of IM and its long-term efficacy in children are not well defined. The purpose of this multicentre study is to report on the long-term results of high-dose IM (340 mg/m2 /d) in CML patients in chronic phase (CP-CML) aged <18 years at diagnosis. A total of 47 CP-CML patients with a median age at diagnosis of 11 years 9 months were enrolled in nine Italian centres. Complete cytogenetic response was achieved in 91.5% of the evaluable patients at a median time of 6 months. BCR-ABL1 International Scale ≤ 0.1% (major molecular response; MMR) and ≤0.01% (molecular response; MR) at 12 months were 66.6% and 33%, respectively. During follow-up, MMR and MR were achieved in 78.6% and 61% of children, respectively. IM was safely discontinued in 3 long-term treated children with a durable MR. Twelve patients (eight cytogenetic/molecular responders) underwent stem cell transplantation. The progression-free survival probabilities at 96 months for responding patients who continued IM and for those transplanted were 60% and 50%, respectively. After a median follow-up of 52 months (range 3-146), all patients are alive. High-dose IM is a long-term effective therapy in children and adolescents with CP-CML.

Keywords: BCR-ABL1; childhood; chronic myeloid leukaemia; imatinib; tyrosine kinase inhibitors.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Antineoplastic Agents / administration & dosage*
  • Benzamides / administration & dosage*
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Imatinib Mesylate
  • Italy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Male
  • Piperazines / administration & dosage*
  • Pyrimidines / administration & dosage*
  • Stem Cell Transplantation
  • Survival Rate

Substances

  • Antineoplastic Agents
  • BCR-ABL1 fusion protein, human
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl