Relationship between minimal residual disease and prognosis in acute leukemia patients in remission
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摘要: 目的: 研究急性白血病缓解期微小残留病灶(MRD)变化情况及其与预后的关系。方法: 对62例成年人急性淋巴细胞白血病(ALL)完全缓解患者(男34例,女28例)和126例成年人急性髓细胞白血病(AML)完全缓解患者(男67例,女59例),采用流式细胞术检测骨髓中MRD,与传统骨髓形态学检查结果进行比较。所有患者平均跟踪随访6(3~24)个月,记录MRD值的变化及相应的预后情况:是否复发及复发时间,骨髓确诊复发的时间,不同性别、年龄、难治性的复发情况。结果: ALL患者共有骨髓标本174份,MRD阳性146份,其中31份标本MRD ≥ 0.05,MRD阴性(MRD<0.001)28份。骨髓确诊复发24例。其中18例患者MRD持续阳性于9~24个月后出现骨髓复发,较骨髓确诊复发平均提前6个月。预测ALL不同治疗时间MRD诊断复发的敏感性均为100%;特异性1~12个月为76.9%,13~24个月为77.8%,差异无统计学意义(P>0.05)。126例AML患者检测完全缓解时MRD共126次,骨髓确诊复发21例。ALL和AML患者均可见MRD>0.001时复发率明显升高,而复发率与性别、年龄、是否为难治性无关(P>0.05),MRD ≥ 0.01患者的复发时间明显短于MRD ≤ 0.005和0.005
P<0.05)。结论: 利用流式细胞术能够对急性白血病缓解期患者进行MRD检测预测复发,MRD可作为预后评价的敏感指标。MRD>0.001时复发的可能性大。连续定期动态观察对复发提示、预后预测及个体化治疗的指导有重要意义。 Abstract: Objective: To observe the change of minimal residual disease (MRD) in acute leukemia patients in remission,and explore the relationship between MRD and the prognosis.Method: Sixty-two cases of adult acute myeloid leukemia (ALL) with complete response (male 34,female 28) and 126 cases of adult acute myeloid leukemia (AML) with complete response (male 67,female 59) were enrolled.We used flow cytometry technology (FCM) to detect MRD in bone marrow,and the results were compared with traditional bone marrow cell morphology.After average 6-month follow-up (3 to 24 months) of all the patients,we recorded the changes of MRD value and prognosis including relapse and relapse time,relapse rate among different gender,age and refractory status.Result: In 174 bone mallow samples of ALL patients,MRD were positive in 146 samples,including 31 samples with MRD ≥ 0.05,and 28 samples with MRD<0.001 (MRD negative).Twenty-four patients were diagnosed as relapse by bone marrow cell morphology,of which 18 were finally diagnosed as relapse 9 to 24 months (average 6 months) after continually positive in MRD.The average sensitivity of MRD assay in predicting relapse were all 100% and the specificity were 76.9% in 1 to 12 months group,and 77.8% in 13 to 24 months group,showing no significant difference between two groups (P>0.05).A total of 126 patients with AML in complete remission detected MRD 126 times,of which 21 patients were diagnosed as relapse by bone marrow cells morphology.ALL and AML patients with MRD>0.001 had obviously higher recurrence rate,and the recurrence rate had no relation with the gender,age and refractory (P>0.05).MRD ≥ 0.01 patients had significantly shorter relapse time than MRD ≤ 0.005 and 0.005Conclusion: Relapse of acute leukemia can be predicted by MRD detection with the use of FCM.MRD can be used as a sensitive index for the evaluation of prognosis.When MRD is higher than 0.001,the risk of relapse is higher.Continuous dynamic monitor of MRD has important significance in predicting the recurrence and prognosis and directing the individualized treatment. -
Key words:
- minimal residual disease /
- remission of acute leukemia /
- prognosis
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