Minimal residual disease as biomarker for optimal biologic dosing of ARA‐C in patients with acute myeloid leukemia

Abstract

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 5 78) or HDAC (n 5 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 5 0.007) and consolidation (44% vs. 18%, P 5 0.002).Respective median residual leukemic cell counts with SDAC and HDAC use were 1.5 3 10 23 and 4 3 10 23 (P 5 0.033) after induction and 5.7 3 10 24 and 2.9 3 10 23 (P 5 0.008) after consolidation. Based on ARA-C schedule and post-consolidation MRD status, the four patient groups (SDAC-MRD 2 , HDAC-MRD 2 , SDAC-MRD 1 , and HDAC-MRD 1 ) displayed 5-year overall survival rates of 60%, 33%, 24%, and 42% (P 5 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.

Gemtuzumab Ozogamicin (GO) Inclusion to Induction Chemotherapy Eliminates Leukemic Initiating Cells and Significantly Improves Survival in Mouse Models of Acute Myeloid Leukemia

“…The poor long-term prognosis of standard induction (DA) therapy correlated with the levels of minimal residual disease (MRD) [4] . A high level of MRD was found to correlate with a higher percentage of chemoresistant leukemic stem cells, which are characterized by their inherent ability for self-renewal, in the bone marrow (BM) of AML patients treated with induction therapy [5] , [6] .…”

Minimal Residual Disease in Acute Myeloid Leukemia of Adults: Determination, Prognostic Impact and Clinical Applications.

“…To explore this hypothesis, we carried out a retrospective analysis of 130 patients who achieved an mCR after one cycle of either standard dose (SDAC) or high doses of cytarabine (HDAC). 59 We observed that the SDAC regimen was associated with a greater MRD-negativity frequency. In 178 patients, who achieved CR after intensive induction, the MRD level assessed at days 16–18 after induction, was associated with outcome.…”

The prognostic value of hematogones in patients with acute myeloid leukemia

“…It is of particular importance to identify patients with high risk of relapse and death. While AMLs with positive MRD assessed by flow cytometry are well‐known to have dismal prognosis , the prognosis of MRD negative patients depends on other prognosis factors such as ELN classification, age and leukocytosis.…”