Treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia with imatinib combined with a paediatric-based protocol

Br J Haematol. 2012 Aug;158(4):506-14. doi: 10.1111/j.1365-2141.2012.09182.x. Epub 2012 Jun 1.

Abstract

Although the combination of tyrosine kinase inhibitors with chemotherapy is widely used for young adults with Philadelphia chromosome positive-acute lymphoblastic leukaemia (Ph+ ALL), the outcome and safety of this combination using intensive paediatric-based protocols has not been well described. The clinical course of 32 adults age 18-60 years with Ph+ ALL treated with a paediatric-based protocol plus imatinib was evaluated. The complete response rate was 94%. Grade 3-4 infections, neuropathy, myopathy and liver function abnormalities were common, resulting in major treatment delays and dose reductions, and declines in performance status (physical deconditioning), particularly in patients aged 41-60 years. Median and 3-year overall survival (OS) was 40·7 months and 53%, respectively, and median and 3-year even-free survival (EFS) was 30·1 months and 50%, respectively. OS and EFS were inferior in deconditioned patients. Of 16 patients who underwent haematopoietic stem cell transplantation (HSCT) in first complete remission, six died of non-relapse complications. There was no significant difference in OS and EFS between transplanted and non-transplanted patients, based on an intention-to-treat and time-to-donor identification analysis. The combination of imatinib with a paediatric-based regimen in adults produced high response rates, but was associated with considerable toxicity and high non-relapse mortality post-HSCT.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzamides
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Imatinib Mesylate
  • Male
  • Middle Aged
  • Piperazines / administration & dosage
  • Piperazines / adverse effects
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Prognosis
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate