Possibilities for tailored and targeted therapy in paediatric acute myeloid leukaemia

The clinical outcome of acute myeloid leukaemia (AML) in children has improved considerably using intensive chemotherapy and/or stem cell transplantation. This leads to cure in 50-70% of patients, and also results in significant morbidity and mortality. Hence, we need other ways to improve the cure rate. This review discusses possibilities for tailored therapy, reviewing in vitro cellular drug sensitivity data. The results provide suggestions regarding the adaptation of clinical protocols in certain AML subgroups, although further clinical studies will show whether this is effective. Secondly, we review type 1 genetic abnormalities (such as receptor tyrosine kinase mutations) that result in enhanced survival and proliferation of leukaemic cells, which can be detected in approximately 50% of paediatric AML samples, and are non-randomly associated with French-American-British type and cytogenetic subgroups. FLT3 internal tandem duplication is associated with poor clinical outcome, and may be used for risk-group stratification. The first results with small molecule inhibitors in adult AML do not suggest their use in children as yet. International collaboration is needed to further improve outcome by developing treatment protocols for subgroups of paediatric AML.