动态监测微小残留病对急性白血病预后的临床意义

Clinical significance of dynamically monitoring minimal residual disease in prognosis of acute leukemia

目的探讨监测微小残留病（MRD）在急性白血病（AL）复发预测及指导临床治疗中的意义。方法选取2011年1月至2013年12月该科收治的36例初治AL患者,共采集160份骨髓液及外周血液标本,利用四色多参数流式细胞术（FCM）进行MRD检测。以CD45/SSC设门,选用2~3组四色抗体组合,从首次诱导化疗结束,每1~3个月进行MRD检测1次,动态监测MRD水平的变化与AL复发之间的相关性。结果按诱导治疗第1次结束时的MRD水平分为三组：MRD〉1×10-2组（22例）、MRD为1×10-4~1×10-2组（6例）、MRD〈1×10-4组（8例）。MRD〉1×10-2组复发率[81.8%（18/22）]明显高于MRD〈1×10-4组[12.5%（1/8）],差异有统计学意义（P=0.003）,而MRD为1×10-4~1×10-2组复发率[50.0%（3/6）]与MRD〈1×10-4组比较,差异无统计学意义（P=0.059）。MRD〈1×10-4预后良好。另30例检测外周血和骨髓MRD的AL患者中,外周血MRD〉1×10-214例,MRD为1×10-4~1×10-27例,MRD〈1×10-49例;骨髓MRD〉1×10-28例,1×10-4~1×10-210例,〈1×10-412例。结论 AL患者MRD阳性比形态学复发出现时间早,因此,动态监测MRD对AL预测复发和指导个体化治疗有重要意义。

Objective To investigate the clinical significance of dynamically monitoring the minimal residual disease （MRD） in predicting the recurrence and guiding the clinical therapy of acute leukemia（AL）. Methods 36 cases of initial AL in the hematology department of our hospital from January 2011 to December 2013 were selected and their bone marrow and periph eral blood specimens were collected for detecting MRD by using the 4-color muhiparameter flow cytometry （FCM）. The 2-3 groups of 4-color antibodies combination were selected with CD45/SSC as gating, the MRD detection was performed once per 1-3 months after the end of the first induction chemotherapy, moreover the correlation between the change of MRD level with AL recurrence was dynamically monitored. Results The cases were divided into 3 groups according to the MRD level after the end of the first induction therapy：MRD 〉1×10^-2 group（22 cases） ,MRD 1×10^-4-1×10^-2（6 cases） and MRD〈1×10^-4（8 cases）. The recurrence rate in the MRD〉1×10^-2 group was 81.8% （18/22） ,which was significantly higher than 12.5% （1/8） in the MRD〈1×10^-4 group,the difference was statistically significant （P=-0.003） ,which in the MRD1×10^-4-1×10^-2 group was 50.00%（3/6） ,showing no statistical difference compared with the MRD〈1×10^-4 group（P=0.059）. The prognosis in MRD〈1×10^-4 was better. Among other 30 cases of AL for detecting peripheral blood and bone morrow MRD, 14 cases had peripheral blood MRD〉1×10^-2,7 cases had peripheral blood MRD 1×10^-4-1×10^-2, 9 cases had M RD〈1×10^-4,8 cases had bone morrow MRD 〉1×10^-2,10 cases had bone morrow M RD 1×10^-4-1×10^-2 and 12 cases had bone morrow MRD〈1×10^-4. Conclusion The MRD positive in AL patients appears early than the morphology recurrence, therefore, dynamically monitoring MRD has an importance significance to predict the AL recurrence and guide the individualized therapy.