"InDACtion" vs "3+7" Induction in AML

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The overall survival (OS) of older AML patients has not been improved during the last decades with intensive chemotherapy based on cytarabine combined with an anthracycline ("3+7"). Next generation sequencing technology reveals that mutations in genes involved in epigenetics are frequently mutated i...

The overall survival (OS) of older AML patients has not been improved during the last decades with intensive chemotherapy based on cytarabine combined with an anthracycline ("3+7"). Next generation sequencing technology reveals that mutations in genes involved in epigenetics are frequently mutated in AML (e.g. DNMT3a), suggesting an important role of epigenetics in the pathophysiology of AML. Decitabine (given in a 5-day schedule) has been shown to be superior to low-dose Ara-C. A retrospective analysis revealed that epigenetic therapy (either azacitidine or decitabine) is associated with similar survival rates as intensive chemotherapy in older patients (n=671) with newly diagnosed AML. The recently published encouraging phase 2 data with the 10-day decitabine schedule suggests that decitabine results in similar CR rates compared with intensive chemotherapy. Allogeneic transplantation (alloHCT) also offers the opportunity for cure among older AML patients, therefore treatment strategies should aim to allograft older AML patients. Decitabine treatment can lead to very interesting cure rates when used as "bridging" to allografting. Based on the data summarized above, we hypothesize that decitabine at a daily dose of 20 mg/m² starting with the 10-day schedule followed by an alloHCT or by continuation of 5-days decitabine cycles is superior to conventional intensive chemotherapy in older AML patients.

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