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Imatinib (Glivec°) and acute lymphoblastic leukaemia in children: prolonged survival in Philadelphia chromosome-positive cases

FEATURED REVIEW In children with acute lymphoblastic leukaemia harbouring the Philadelphia chromosome, historical comparisons suggest that adding imatinib to chemotherapy significantly increases the 5-year overall survival rate. Imatinib must continue to be evaluated in this setting but clearly represents a therapeutic advance.
Full review (2 pages) available for download by subscribers.

Abstract

  • About 5% of patients with acute lymphoblastic leukaemia have the abnormal “Philadelphia” chromosome associated with a poor prognosis.
     
  • Initial chemotherapy takes place in several phases and lasts a total of 2 to 3 years. Many Philadelphia chromosome-positive patients subsequently undergo allogeneic haematopoietic stem cell transplantation.
     
  • Imatinib (Glivec°, Novartis Pharma), a tyrosine kinase inhibitor, is authorised in the European Union for the treatment of children with Philadelphia chromosome-positive acute lymphoblastic leukaemia, in combination with first-line chemotherapy. It was already authorised in the same conditions in adults.
     
  • Two non-comparative trials of imatinib in children showed a roughly 40% to 50% improvement in the 5-year survival rate by comparison with historical controls who had received chemotherapy alone, an average of 10 years previously. In these two trials imatinib was introduced either during or immediately after the induction phase.
     
  • The impact of imatinib on the subsequent need for transplantation has not been established, and neither has the optimal dosage.
     
  • Imatinib has potentially serious adverse effects, which add to those of chemotherapy. The long-term safety of imatinib in children is poorly documented.
     
  • Imatinib tablets may be dispersed in water or apple juice, but the lack of a specific paediatric form hinders precise dose adjustment for young children.
     
  • In practice, imatinib should be used to treat children with Philadelphia chromosome-positive acute lymphoblastic leukaemia. As this is a rare condition, all imatinib-treated patients should be included in a registry.  

©Prescrire 1 Febuary 2015

"Imatinib and acute lymphoblastic leukaemia in children. Prolonged survival in Philadelphia chromosome-positive cases" Prescrire Int 2015; 24 (157): 38-39 (Pdf, subscribers only)

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