Minimal Residual Disease as Biomarker for Optimal Biologic Dosing of ARA-C in Patients with Acute Myeloid Leukemia

We assessed by flow cytometry minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) given standard-dose (SDAC) and high-dose ARA-C (HDAC) regimens. Of 163 patients enrolled, 130 (median age, 45 years; range, 18-59 years) qualified for analysis, all achieving complete remission after treatment with SDAC (n=78) or HDAC (n=52) plus etoposide and daunorubicin. Consolidation consisted of intermediate-dose ARA-C and daunorubicin. MRD negativity was significantly more frequent in the SDAC vs. HDAC arm after both induction (37% vs 15%, p=0.007) and consolidation (44% vs. 18%, p=0.002). Respective median residual leukemic cell counts with SDAC and HDAC use were 1.5×10e-3 and 4×10e-3 (p=0.033) after induction and 5.7×10e-4 and 2.9×e10-3 (p=0.008) after consolidation. Based on ARA-C schedule and post-consolidation MRD status, the four patient groups (SDAC-MRD- , HDAC-MRD- , SDAC-MRD+ , and HDAC-MRD+ ) displayed 5-year overall survival rates of 60%, 33%, 24%, and 42% (p=0.007), respectively, with 24%, 35%, 74%, and 48% (p<0.0001) respective cumulative incidence of relapse estimates. MRD may serve as a biomarker for optimal biologic dosing of ARA-C, and SDAC regimen appears to yield more frequent MRD negativity.