Acute Myeloid Leukaemia: predicting outcome
Disease aggressiveness and treatment responses in AML patients vary widely, despite cytogenetic prognostic categories at diagnosis broadly defining patient outcome.
This prompted us to examine new ways to stratify risk and guide therapy.
Our first study showed that preserved immune function within the bone marrow, as detected by higher T-lymphocytes at diagnosis, led to markedly improved survival from AML. The technique used is relatively cheap and readily available, and the findings suggest targeting the immune system for both therapy and further research.
The second study found that some mutations (IDH1/2, DNMT3A) within leukaemia cells persist after therapy despite patients achieving disease remission by all other criteria. These ‘founder mutations’ are present in marrow cells prior to the development of acute leukaemia. In some of the cases studied, a PCR-based test performed on the Sequenom platform on sequential samples showed that rising levels of the DNMT3A mutation predicted relapse prior to any other indicator of leukaemia.
These results mirror those found in larger overseas studies and support molecular testing for ‘founder mutations’ to guide therapy in routine clinical practice.