Approximately 3-5% of cases of ALL in children and adolescents are characterised by the presence of the Philadelphia chromosome (translocation t(9;22), molecular equivalent: BCR-ABL fusion). While historically the prognosis of affected children treated with conventional chemotherapy, supplemented if possible by allogeneic haematopoietic stem cell transplantation (HSCT), was extremely poor with cure rates of less than 50%, the systematic introduction of the tyrosine kinase inhibitor (TKI) imatinib, which was tested in a large European (EsPhALL) and several U.S. multicentre studies (COG), has led to the fact that more than half of patients can now be cured even without HSCT. However, the chemotherapy chosen in both consortia was highly intensive and accordingly associated with the occurrence of severe therapy toxicity including life-threatening infections; the use of high cumulative doses of anthracyclines and high-dose cytarabine as well as ifosfamide and etoposide also entails a high risk of severe long-term consequences. A reduction in these undesirable side effects while maintaining an acceptably low recurrence rate would represent a relevant advance in the treatment of affected children and adolescents.
