Clinical Study On Dynamic Detection Of Minimal Residual Disease In Acute Myeloid Leukemia By Multiparameter Flow Cytometry

Objective: The level of minimal residual disease(MRD)in patients with acute myeloid leukemia(AML)after treatment was dynamically detected by 8-color flow cytometry,and the difference of recurrence and survival among patients with different MRD changes was compared to evaluate the prognostic significance of dynamic flow cytometry detection of MRD.Methods: 282 AML patients with initial remission were retrospectively analyzed.MRD was dynamically detected by 8-color flow cytometry.The MRD threshold for predicting recurrence by MFC detection in our center was determined by the receiver operating characteristic curve(ROC),the median time from MRD positive to clinical recurrence was analyzed.Compare the difference of patients’ recurrence-free survival time(RFS)and overall survival time(OS)in different MRD change groups,the clinical characteristics of MRD-negative patients and MRD-positive patients were analyzed by univariate analysis,and Cox regression analysis was performed on the factors that affect the patient’s hematological recurrence.Results:(1)The ROC curve determines that the MFC-MRD threshold for predicting recurrence is 0.1%,52.45% of MRD-positive patients relapsed,and the recurrence rate of negative patients was 35.97%.The recurrence rate of the former was significantly higher than that of the latter,P = 0.005.(2)Patients in the MRD persistent positive group and negative to positive group relapse earlier than those in the positive to negative group and negative positive fluctuation group(P = 0.000).(3)Survival analysis suggested that the OS and RFS time of patients with persistent positive MRD were obviously shorter than those in the persistent negative group,positive to negative group,and negative-positive fluctuation group(P<0.005).There was no obvious difference in OS and RFS between the MRD negative to positive group and the MRD persistent positive group(P>0.005).The MRD negative group and the MRD positive to negative group had no obvious difference in OS and RFS(P>0.005).(4)50 out of 139 MRD negative patients had recurrence.Univariate and Cox regression analysis suggested that as the WBC level increased,the patient’s risk of recurrence increased(95%CI 1.000-1.007,P=0.040),and the risk of recurrence of patients who received HSCT was 0.200 times that of those who did not receive HSCT(95% CI 0.047-0.844,P= 0.028).The risk of recurrence for patients in the high-risk group was higher than that of patients in the lower-risk group,the former was 3.145 times that of the latter(95%CI 1.351-7.321,P=0.008).(5)Of the 143 MRD-positive patients,75 relapsed.Univariate and Cox regression analysis showed that the risk of recurrence for patients who received HSCT was 0.263 times that of those who did not receive HSCT(95%CI0.120-0.577,P=0.001).If the patient’s MRD level is continuously positive or MRD negative to positive,the risk of recurrence is 4.554 times that of patients with MRD positive to negative or MRD negative-positive fluctuation(95 % CI 2.808-7.385,P=0.000).Conclusion:(1)In this study,the threshold of MFC-MRD detection for predicting recurrence was 0.1%,and the prognosis of patients with different MRD changes was significantly different.Using 8-color flow cytometry to monitor the dynamic changes of MRD in AML patients after treatment was helpful to timely identify the patients with imminent recurrence and poor prognosis,and accurately guide the intervention treatment of patients.(2)After the first occurrence of MRD positive in patients with persistent positive MRD and negative to positive MRD group,the recurrence was earlier than that in patients with MRD positive to negative and MRD negative to positive fluctuating group,and the time of OS and RFS was also significantly shorter than that in other patients.(3)The prognosis of patients with negative MRD after initial treatment is similar to that of patients with persistent positive MRD if the MRD turns positive and remains positive during the treatment;the prognosis of patients with positive MRD after initial remission who have negative MRD and remain negative after treatment is similar to that of patients with persistent negative MRD.(4)Receiving hematopoietic stem cell transplantation is a protective factor for patient recurrence.Elevated peripheral blood white blood cell level at initial diagnosis and risk stratification into high-risk group are risk factors for recurrence in MRD negative patients,and persistent positive or negative to positive MRD is the risk factor for recurrence of patients with MRD positive.