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The tyrosine kinase inhibitor (TKI) imatinib has become an integral part of front-line therapy for Philadelphia chromosome-positive acute lymphoblastic leukaemia, with remission rates exceeding 90% irrespective of whether imatinib is given alone or combined with chemotherapy. Treatment outcome with imatinib-based regimens has improved compared with historic controls, but most patients who do not undergo allogeneic stem cell transplantation (SCT) eventually relapse. Second-generation TKI, e.g. dasatinib and nilotinib, show activity against most of the bcr-abl tyrosine kinase domain mutations involved in acquired imatinib resistance, but clinical benefit is generally short lived. Accordingly, SCT in first complete response is considered to be the best curative option. Strategies to improve outcome in patients ineligible for transplantation as well as after SCT include front-line treatment with more effective TKI to increase molecular response rates. Following SCT, the pre-emptive use of imatinib appears to reduce the relapse rate. Novel immunotherapeutic interventions and combinations of TKI are also being explored.