| Background and ObjectivesComplete remission(CR) rate of acute leukemia (AL)in recent years has increased obviously, but still a part of patients relapse, and the underlying reason of relapse is the minimal residual disease(MRD) in patients after complete remission. Minimal residual disease refers to the state of leukemia patients who remains a small amount of leukemia cells in the body after complete remission after treatment, and is an independent prognostic factor that is closely related to the relapse. Monitoring minimal residual disease has the very vital significance in guiding treatment, predicting relapse, evaluating prognosis and other aspects. The methods of detecting MRD in the clinical contain cytogenetics (fluorescence in situ hybridization is included), polymerase chain reaction (PCR), flow cytometry (FCM) and so on. And among them, detecting MRD by FCM is rapid, simple, economical, sensitive and specific, so it has a high practical value in the clinical work. Several research institutes at home and abroad detecting MRD by FCM in AL patients were reported. But most of these studies were to choose one or several time points after chemotherapy detecting MRD to analyze its relation with relapse and few of MRD tendency were studied. This study was purposed to investigate dynamically monitoring the changing trends of MRD by multiparameter FCM in patients with acute leukemia after complete remission, and analyze the relation between the MRD level after induction therapy and the first consolidatory therapy with the prognosis.Objects and Methods1. From October2010to May2012,58cases of AL patients (including45cases of AML patients and13cases of ALL patients) were selected in the Hematology Department of the First Affiliated Hospital of Zhengzhou University.45cases of AML patients including25males (55.6%) and20females (44.4%) were involved in this study, the median age was41(13～66) years and the mean follow-up time was8.5(3-21) months. Among45cases of AML patients,1case (2.2%) was Mo,3cases (6.7%) were Mi,26cases (57.8%) were M2,4cases (8.9%) were M3,5cases (11.1%) were M4,5cases (11.1%) were M5and1case (2.2%) were M6.13cases of ALL patients including7males (53.8%) and6females (46.2%) were involved in this study, the median age was27(15-68) years and the mean follow-up time was8.7(3-21) months. Among13cases of ALL patients,11cases (84.6%) were B-ALL and2cases (15.4%) were T-ALL.2. Forty-five cases of AML patients and13cases of ALL patients were regularly monitored for MRD in bone marrow by FCM and their bone marrow morphology were observed by light microscopy at the same time which continued to relapse or to follow-up deadline. The average follow-up period was9months (3-21months), the average MRD level was achieved. And the prognostic value of MRD level at different time points after CR in AL patients was analyzed and summarized. MRD≥1%was defined as positive, otherwise, as negative.3. The data was analyzed using Software SPSS17.0. Sample mean was compared by T test, qualitative date was analyzed by chi-square test, and the survival curve was compared by Kaplan-Meier. Statistical significance was defined as P below0.05.Results1. MRD levels and the tendency:The results showed that the maximum and minimun MRD levels of45cases of AML patients were9.57%and0.01%respectively, the average was0.67%; the maximum and minimum MRD levels of13cases of ALL patients were7.9%and0.0016%respectively, the average was0.99%. The mean MRD levels after CR between ALL and AML did not have significant difference (0.99%vs0.67%, P=0.17). The maximum and minimun MRD levels of11cases of B-ALL patients were7.9%and0.0045%respectively, the average was1.03%; the maximum and minimum MRD levels of2cases of T-ALL patients were2.25%and0.0016%respectively, the average was0.82%. The mean MRD levels after CR between B-ALL and T-ALL did not have significant difference (1.03%vs0.82%, P=0.69). With the increase of number of chemotherapy and the extension of treatment time, the MRD levels of58cases of AL patients after CR were in a downward trend overall, but the volatility was quite large. And some MRD negative patients became MRD positive in the process of consolidation treatment, while their bone marrow cell morphology were still in CR. After one or two strong chemotherapy, MRD turned negative again.2. The relation between MRD levels at different time points after treatment and relapse as well as the relapse-free survival analysis:Among44cases of MRD levels after induction therapy, the relapse rate of MRD(+) group was53.3%(8/15), the relapse rate of MRD(-) group was10.3%(3/29), and the relapse rate of MRD(+) group was higher than MRD(-) group (X2=7.58, P=0.006); the difference of relapse-free survival time of two groups compared by Kaplan-Meier had no statistical significance (P>0.05). Among58cases of MRD levels after the first consolidatory therapy, the relapse rate of MRD(+) group was62.5%(5/8), the relapse rate of MRD(-) group was16.0%(8/50), and the relapse rate of MRD(+) group was higher than MRD(-) group (X2=6.11, P=0.013); the difference of relapse-free survival time of two groups compared by Kaplan-Meier had statistical significance (P=0.005). Median relapse-free survival time of MRD(+) group was6months and median relapse-free survival time of MRD(-) group was8months. Conclusion1. MRD is one of the important indicators for monitoring remission and relapse of acute leukemia and dynamically monitoring the changes of MRD of AL patients after complete remission by FCM can provide the basis for clinical individual therapy.2. MRD detected by FCM has a large range (10-6～10-2), which can not be used as a single indicator of complete remission.3. When MRD≥1%after induction therapy and the first consolidatory therapy, the relapse rate significantly increases, MRD can be used as a sensitive indicator for prognosis. |
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