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Innere Medizin 1. März 2009

Tailored therapeutic approaches in acute myeloid leukaemia

PURPOSE OF REVIEW: In recent years new molecular markers have emerged as significant prognostic parameters and as potential targets for molecularly targeted therapy in acute myeloid leukaemia (AML). Prognostic markers, however, cannot guide the decision for a specific treatment since they are associated with a differential outcome regardless of the given treatment. In contrast, predictive markers indicate a treatment benefit in patients that are characterized through these markers. Thus predictive markers can guide clinical decision-making. RECENT FINDINGS: In young adults mutations of the NPM1 (NPM1mut) gene in the absence of concurrent FLT3-ITD (FLT3-ITDneg) mutations have impressive prognostic and beyond prognostication also predictive properties. This NPM1mut/FLT3-ITDneg genotype predicts equivalent favourable outcome after intensive chemotherapy and allogeneic stem cell transplantation, whereas in the absence of this marker clinical outcome was significantly improved after an allogeneic transplantation. In addition, within a retrospective study performed in older adults the same genotype predicted a significantly improved outcome if all-trans retinoic acid was added to intensive chemotherapy. SUMMARY: The discovery of new prognostic and predictive markers has increased our understanding of leukaemogenesis thus leading to an improved prognostication. Furthermore, current clinical research focusing on the assessment of genotype-specific therapy may translate into an increase in the cure rate.

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