Assignment: Cytarabine Infusion
The typical dose and schedule includes either daunorubicin (60 or 90 mg/m2 on days 1, 2 and 3) or idarubicin (10–12 mg/m2 on days 1, 2 and 3) given with seven days of continuous cytarabine infusion (100 mg/m2/daily for one week (days 1 through 7). The goal of induction chemotherapy is to achieve morphologic complete remission (CR), which is defined as: (1) <5% blasts in bone marrow aspirate sample with marrow spicules and with a count of ≥200 nucleated cells (no blasts with Auer rods or persistence of extramedullary disease);
absolute neutrophil count (ANC) >1000/µL, and (3) platelets ≥ 100,000/µL . Young, de novo, AML patients achieve CR in 65%–73% using standard induction with “7 + 3” while only 38%–62% of patients over 60 years of age with AML achieve CR [64,65,66]. Several trials have now shown that higher dose of anthracycline (90 versus 45 mg/m2) in both younger and older fit adults (from 60 to 65) results in higher CR rates and increases the duration of OS [65,66]. Concerns about toxicity of high-dose daunorubicin and the wide use of the 60-mg/m2 dose as a newer “standard,” led the United Kingdom (UK) National Cancer Research Council (NCRC) to conduct a prospective randomized trial with the goal to compare daunorubicin at 60 vs. 90 mg/m2 in the induction of 1206 AML patients . In this study there was no benefit of using higher dosing (90 mg/m2) over 60 mg/m2 across all subgroups . However there are some caveats to consider in this trial. In particular, the cumulative dose of anthracyclines in the low dose arm (60 mg/m2) was equivalent in the United Kingdom National Cancer Research Institute (UK NCRC) trial to the higher dose (90 mg/m2) of the other clinical trials due to multiple courses of anthracycline. In addition the UK NCRC trial has a shorter follow up . Thus, it is clear that 45 mg/m2 of daunorubicin seems insufficient and 60 mg/m2 is not inferior to 90 mg/m2 with less associated toxicity. Patients found to have a FLT3 mutation should be treated with a FLT3 inhibitor (discussed in more detail below), such as midostaurin, added to standard induction therapy .
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