Optimal Time Point for Measurable Residual Disease (MRD) Assessment in Acute Myeloid Leukemia Patients

Introduction: Measurable residual disease (MRD) is currently performed for the prediction of prognostic outcomes in acute myeloid leukemia (AML) and multiparameter flow cytometry (FCM) is one method that is widely applied for detecting MRD. Nevertheless, the optimal time intervals for clinically relevant sequential measurements of MRD are not yet established. The European LeukemiaNet (ELN) recommendation for MRD assessment by FCM analysis has suggested that MRD level below 0.1% is defined as MRD-negative. A retrospective cohort study was conducted to investigate the optimal time point of MRD assessment for the prediction of AML relapse, and to identify FCM markers associated with AML relapse. The correlation between MRD status and disease-free survival (DFS) in AML patients is also studied. Methods: We enrolled 68 adult patients diagnosed with AML who achieved complete remission (CR) between March 2017 and March 2023. The 10-color FCM was performed at diagnosis and during AML treatment. The target cell surface antigens listed in this panel were CD2, CD4, CD7, CD11b, CD13, CD15, CD18, CD19, CD25, CD33, CD34, CD38, CD44, CD45, CD54, CD56, CD64, CD94, CD96, CD117, CD123, CD133, CD371, NG2, and HLA-DR. MFC-MRD detection was done by using leukemia-associated immunophenotype (LAIP) and different from normal (DFN) approach. MRD level below 0.1% is defined as MRD-negative (MRD-). Sequential MRD monitoring was done until relapsed disease, underwent stem cell transplantation (SCT), or died. Results: Of 68 patients, 50% were males and the median age was 55 years (range, 20-78 years). Favorable, intermediate, and unfavorable-risk AML were seen in 21%, 63%, and 16%, respectively. Fifty-seven and thirty-five percent of AML patients received 7+3 and 5+2 induction chemotherapy, respectively. Relapse rate (RR) was found in 39% and 49% of AML patients with MRD-positive (MRD+) by LAIP and DFN approaches, respectively. The highest RR was observed in AML patients with MRD+ after induction chemotherapy (60%) compared with those after both induction and consolidation therapy (48%), MRD+ after consolidation chemotherapy (27%), and MRD- after both induction and consolidation therapy (35%). The median DFS and OS were found at 35 and 51 months, respectively. Median DFS tended to be longer in AML patients with post-induction MRD- (56 months) than those with MRD+ (16 months), p= 0.089, AML patients with MRD+ after induction chemotherapy, both induction and consolidation therapy, and MRD- after both induction and consolidation therapy had median DFS at 16, 45, and 35 months, respectively. Shorter DFS was significantly detected in MRD+ patients with CD2 expression after induction and first cycle of consolidation therapy compared to those without CD2 expression, 9 and 45 months (p= 0.028) and 7 and 56 months (p= 0.007), respectively. Conclusions: MRD status after induction chemotherapy was associated with relapsed rate and DFS. CD2 expression was significantly associated with shorter DFS in AML patients with MRD+ after induction and the first cycle of consolidation therapy.

No relevant conflicts of interest to declare.