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Gradual but definite progress has been made in the treatment of younger adults with acute myeloid leukaemia (AML) [1–3], except those 25–30% with high-risk disease. For them the best approach is a myeloablative allogeneic transplant; however, even the transplant option provides only a 30% chance of cure, and has been limited to younger patients who have a donor. The point at which a patient is recognised to be at high risk is usually after the first course of induction treatment has been given when the most useful prognostic data is to hand. These patients represent an important unmet therapeutic need for which there is no specific standard of care. The challenge is three-fold. First, for those who will go forward to transplant improving the pre-transplant chemotherapy could reduce the post-transplant relapse rate. Second, better treatment could deliver more patients to transplant who otherwise might relapse before reaching transplant. Third, better treatment is needed for patients for whom a transplant is not available. For relapsed patients the FLAG-Ida (fludarabine/cytosine arabinoside (ara-C)/granulocyte-colony stimulating factor (G-CSF) and idarubicin) is widely used, although it has not been subjected to a randomised assessment. In our Medical Research Council (MRC) AML15 Trial, FLAG-Ida given for the first two treatment courses had a significantly superior anti-leukaemia effect [4]. It therefore appeared logical to continue with FLAG-Ida as consolidation for patients who were identified as high risk. We chose as the comparative treatment to replace ara-C, in a daunorubicin/ ara-C combination, with an alternative nucleoside, clofarabine, which has demonstrated activity in adverse risk patients [5–9]. Following a successful feasibility study combining daunorubicin with clofarabine, we decided to prospectively compare this combination with FLAG-Ida in high-risk patients. The AML17 protocol (ISRCTN55675535) was designed to include untreated de novo or secondary AML and highrisk myelodysplastic syndrome (defined as >10% marrow blasts at diagnosis). The overall treatment plan has been described elsewhere [10] and was conducted in accordance with the Declaration of Helsinki, sponsored by the Cardiff University, and approved by the Wales Research Ethics Committee 3. The age range was between 16 and 61 years, although older patients were permitted if deemed suitable for the potential randomisations. Three hundred and eleven patients were randomised after having received the first induction course, which could have been ADE (Ara-C/ daunorubicin/etoposide) alone (N= 39) or with gemtuzumab ozogamicin (GO) 3 mg/m (n= 29) or 6 mg/m (n= 30) or daunorubicin/Ara-C (DA) with GO 3mg/m (N= 35) or 6 mg/m (N= 22) with the daunorubicin dose being 60 mg/m (n= 78) or 90 mg/m (n= 78). GO was given on * R K Hills hillsrk@cf.ac.uk

A comparison of FLAG-Ida and daunorubicin combined with clofarabine in high-risk acute myeloid leukaemia: data from the UK NCRI AML17 Trial