Imatinib in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia: current status and evolving concepts |
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Authors: | Ottmann Oliver G Wassmann Barbara |
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Affiliation: | 1. Division of Surgical Oncology, Mayo Clinic Arizona, 5777 East Mayo Blvd, Phoenix, AZ 85054, USA;2. Department of Biostatistics, Mayo Clinic Arizona, 5777 East Mayo Blvd, Phoenix, AZ 85054, USA;1. Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA;2. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, CLL Center, 450 Brookline Avenue, Boston, MA 02215, USA;1. OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden – Rossendorf, Germany;2. Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany;3. Helmholtz-Zentrum Dresden – Rossendorf, Institute of Radiooncology – OncoRay, Germany;4. German Cancer Consortium (DKTK), partner site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany;1. Clinic of Hematology and Clinical Immunology, Clinical Centre Niš, Niš, Serbia;2. Faculty of Medicine, University of Niš, Niš, Serbia;3. Mechanical Engineering Faculty, University of Niš, Niš, Serbia |
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Abstract: | Until recently, progress in the treatment of patients with Ph(+) acute lymphoblastic leukaemia (ALL) has been limited, and long-term survival, even with high-dose intensified chemotherapy, is rare. Allogeneic stem cell transplantation is potentially curative, but treatment-related mortality and rate of disease recurrence are substantial. With the advent of the ABL-selective tyrosine kinase inhibitor STI571 (imatinib mesylate, Glivec), it has become apparent that the understanding of crucial leukaemogenic pathways at the molecular level can lead to the development of specific and selective agents. In recent clinical trials, imatinib has demonstrated significant anti-leukaemic efficacy in patients with advanced Ph(+) ALL, in conjunction with a remarkably favourable safety profile. Clinical resistance to imatinib develops rapidly, highlighting the limitations of using imatinib as a single agent; however, the value of imatinib as an element of treatment has become apparent. Resistance mechanisms have already been identified that will enable the development of rational strategies to prevent or overcome resistance. On the basis of available clinical results, combinations of imatinib with established anti-leukaemic agents, as well as with novel, molecularly targeted treatment modalities, will need to be evaluated in advanced Ph(+) ALL. Incorporation of imatinib in the first-line treatment of de novo Ph(+) ALL and in the setting of minimal residual disease is a promising therapeutic approach which is currently being studied in clinical trials. Better understanding of targeted therapies, including strategies based on recruitment of host immune functions, as well as the prudent use of active chemotherapy agents, may eventually improve the outlook for patients with Ph(+) ALL. |
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Keywords: | Philadelphia chromosome acute lymphoblastic leukaemia BCR/ABL STI571 kinase inhibitor targeted therapy stem cell transplantation minimal residual disease |
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