Urgent Cytoreductive Chemotherapy for Newly Diagnosed Patients with AML Is Safe and Feasible and Facilitates Enrollment on Investigational Clinical Trials

Background : AML is a life-threatening, rapidly progressive malignancy that frequently presents with uncontrolled leukocytosis, organ infiltration, and the need for urgent chemotherapy. Recent advances in genomic profiling have identified significant heterogeneity in AML, that is best addressed with individualized, targeted approaches, often on clinical trials. The requisite cytogenetic and molecular data to inform definite treatment, however, is not rapidly available. Studies have suggested that delaying initial therapy in newly diagnosed AML may worsen OS. Implementing formal cytoreduction strategies may allow time for treatment selection and clinical trial enrollment without adversely affecting outcomes. Methods: We piloted an approach with our frontline clinical trials in AML to allow cytoreductive therapy with hydroxyurea (HA) and/or higher doses of Cytarabine (Ara-C) for disease control prior to definitive therapy. 3 frontline chemotherapy protocols were designed to allow HA and up to 2 grams/m2 of Ara-C for urgent disease control prior to starting therapy. We reviewed the feasibility and outcomes of this approach in older and younger pts with newly diagnosed AML treated between April 2014 and May 2020. Results: We reviewed 276 patients, 97 (35%) which received cytoreductive therapy prior to starting definitive therapy. Baseline characteristics of patients who did or did not receive cytoreductive therapy are summarized in Table 1. The median time from presentation to definitive treatment was 6 days (range 1-21 days) and 6 days (1-46 days) in patients with or without cytoreduction, respectively. Patients with cytoreduction had higher median peripheral blasts 44% (Interquartile Range, IQR : 46-79) vs. 6% (IQR: 4-7) than patients without cytoreduction. More patients with cytoreduction were female (64%; p=0.007), ECOG performance status (PS) >1 (27%; p