Acute Respiratory Distress Syndrome.

n engl j med 377;19 nejm.org November 9, 2017 1903 The authors reply: Eskazan speculates that a regimen using daunorubicin at a dose of 90 mg per square meter (with or without midostaurin) would lead to superior outcomes as compared with the regimen of daunorubicin at a dose of 60 mg per square meter plus midostaurin that was used in the CALGB 10603 trial. However, at the time that the trial was designed, neither the results showing the superiority of induction with daunorubicin at a dose of 90 mg per square meter as compared with 45 mg per square meter in FLT3-mutated AML1 nor those suggesting that the higher dose of this anthracycline might be better than 60 mg per square meter in FLT3-mutated AML2 were available. These cited data are derived from retrospective analyses that were not powered to show significant differences. With all the caveats involved in comparing one trial with another, the results with the induction of daunorubicin at a dose of 60 mg per square meter plus midostaurin in the CALGB 10603 trial were, if anything, slightly better than the results with a dose of 90 mg per square meter in the Eastern Cooperative Oncology Group 1900 (E1900) trial1 and the U.K. Medical Research Council AML17 trial.2 A detailed analysis of the effect of NPM1 comutations on the outcome in each group of the CALGB 10603 trial is of interest. In the preliminary trial, concurrent administration of midostaurin and chemotherapy had neither a better sideeffect profile nor better efficacy3 than the sequential schedule used in the CALGB 10603 trial. However, we agree that further exploration of midostaurin schedules and effects on target inhibition are warranted.