Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes Utz Krug, Christoph Röllig, Anja Koschmieder, Achim Heinecke, Maria Cristina Sauerland, Markus Schaich, Christian Thiede, Michael Kramer, Jan Braess, Karsten Spiekermann, Torsten Haferlach, Claudia Haferlach, Steffen Koschmieder, Christian Rohde, Hubert Serve, Bernhard Wörmann, Wolfgang Hiddemann, Gerhard Ehninger, Wolfgang E Berdel, Thomas Büchner*, Carsten Müller-Tidow*, for the German Acute Myeloid Leukaemia Cooperative Group and the Study Alliance Leukemia Investigators† Summary Background About 50% of patients (age ≥60 years) who have acute myeloid leukaemia and are otherwise medically healthy (ie, able to undergo intensive chemotherapy) achieve a complete remission (CR) after intensive chemotherapy, but with a substantially increased risk of early death (ED) compared with younger patients. We verified the association of standard clinical and laboratory variables with CR and ED and developed a web-based application for risk assessment of intensive chemotherapy in these patients. Methods Multivariate regression analysis was used to develop risk scores with or without knowledge of the cytogenetic and molecular risk profiles for a cohort of 1406 patients (aged ≥60 years) with acute myeloid leukaemia, but otherwise medically healthy, who were treated with two courses of intensive induction chemotherapy (tioguanine, standard-dose cytarabine, and daunorubicin followed by high-dose cytarabine and mitoxantrone; or with high-dose cytarabine and mitoxantrone in the first and second induction courses) in the German Acute Myeloid Leukaemia Cooperative Group 1999 study. Risk prediction was validated in an independent cohort of 801 patients (aged >60 years) with acute myeloid leukaemia who were given two courses of cytarabine and daunorubicin in the Acute Myeloid Leukaemia 1996 study. Findings Body temperature, age, de-novo leukaemia versus leukaemia secondary to cytotoxic treatment or an antecedent haematological disease, haemoglobin, platelet count, fibrinogen, and serum concentration of lactate dehydrogenase were significantly associated with CR or ED. The probability of CR with knowledge of cytogenetic and molecular risk (score 1) was from 12% to 91%, and without knowledge (score 2) from 21% to 80%. The predicted risk of ED was from 6% to 69% for score 1 and from 7% to 63% for score 2. The predictive power of the risk scores was confirmed in the independent patient cohort (CR score 1, from 10% to 91%; CR score 2, from 16% to 80%; ED score 1, from 6% to 69%; and ED score 2, from 7% to 61%). Interpretation The scores for acute myeloid leukaemia can be used to predict the probability of CR and the risk of ED in older patients with acute myeloid leukaemia, but otherwise medically healthy, for whom intensive induction chemotherapy is planned. This information can help physicians with difficult decisions for treatment of these patients. Funding Deutsche Krebshilfe and Deutsche Forschungsgemeinschaft. Introduction Complete remission (CR) after intensive induction chemotherapy is a prerequisite for the long-term survival of patients who are diagnosed with acute myeloid leukaemia. 1 In patients who are older than 60 years and otherwise medically healthy—ie, able to undergo intensive chemotherapy—intensive cytarabine-based and anthracycline- based chemotherapy is a valid option and can induce CR and cure. In a randomised phase 3 study by the European Organisation for Research and Treatment of Cancer (EORTC), 2 patients who were 65 years or older with acute myeloid leukaemia had worse survival in the non-intensive chemotherapy group than in the intensive chemotherapy group. However, among patients who are 60 years or older, prognosis is still poor despite intensive chemotherapy, with a median overall survival of less than 1 year. 3–7 In patients with acute myeloid leukaemia who were given intensive induction chemotherapy, the risk of early death (ED) was much higher in those who were 60 years or older than in younger patients, and the CR rate was only about 50% in the older patients compared with 70% in younger patients. 3–7 Synthesis of novel (ie, hypomethylating) drugs —such as azacitidine and decitabine—have extended survival in the older patients without the risks associated with induction chemotherapy. 8,9 However, rates of CR are still low and long-term survival is rare. For patients who are medically healthy, a few variables are known that can be used to estimate the potential benefits and risks associated with intensive chemotherapy. Thus, risk factors such as age at diagnosis, 10 serum concen-tration of lactate dehydro-genase at diagnosis, 11 and a leukaemia secondary to treatment with cytotoxic drugs or an antecedent haematological disease 10,12 are known to correlate with the probability of a patient achieving CR.