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本研究旨在探讨儿童B系急性淋巴细胞白血病(B-ALL)化疗过程中监测不同时间点微量残留病(MRD)水平的临床意义。回顾性分析我院2008年8月至2011年9月以流式细胞术监测3个时间点(即诱导化疗第15天、第33天和治疗第12周)的206例B-ALL患儿骨髓的MRD。结果表明:①206例B-ALL患儿中196例诱导化疗后达完全缓解(CR)(CR率95.1%),其1年与3年无事件生存(EFS)率分别为(92.7±1.8)%和(78.7±3.7)%,其中标危、中危、高危组的3年EFS率分别为(85.6±4.9)%、(82.1±5.8)%和(58.1±9.2)%,3组比较有明显统计学差异(P<0.001);②各时间点上MRD分析显示:MRD水平越高,患儿的3年EFS率越低,其中第15天MRD≥10-2组、第33天和第12周MRD≥10-3组的患儿预后明显不佳;多因素分析显示,第12周MRD≥10-3为独立的不良预后因素;第12周MRD<10-3的3年EFS率为(86.3±4.1)%,MRD≥10-3的3年EFS率为(55.8±9.1)%,差异有统计学意义(P<0.05);③在化疗第33天MRD阴性(MRD<10-4)的98例患儿中有8例复发(复发率为8.2%),在这98例患儿中有39例在第12周时转为阳性(MRD≥10-4),其中5例复发;在第12周时MRD仍为阴性的59例中有3例复发;在第33天MRD阳性的108例患儿中有19例复发(复发率为17.6%),复发率在MRD阳性和阴性两组间差异有统计学意义(P<0.05)。结论:B-ALL患儿治疗过程中以流式细胞术动态监测MRD可有效地评估治疗反应、判断预后、预测复发及指导化疗方案的调整,其中第15天、第33天及第12周的MRD分别以10-2、10-3、10-3为区分危险度最佳界值,第12周MRD≥10-3为独立的不良预后因素。
This study aimed to investigate the clinical significance of monitoring MRD levels in children with B-ALL in chemotherapy. A retrospective analysis of our hospital from August 2008 to September 2011 by flow cytometry at 3 time points (ie induction of chemotherapy on the first 15 days, 33 days and 12 weeks of treatment) in 206 cases of B-ALL children with bone marrow MRD. The results showed that: (1) 196 patients with B-ALL had complete remission (CR) (95.1%) after induction chemotherapy, and the 1-year and 3-year event-free survival rates were 92.7 ± 1.8% And (78.7 ± 3.7)%, respectively. The 3-year EFS rates were (85.6 ± 4.9)%, (82.1 ± 5.8)% and (58.1 ± 9.2)% respectively in the standard, (P <0.001). (2) MRD analysis showed that the higher the MRD level, the lower the 3-year EFS rate. The 15th day MRD≥10-2, the 33rd day and the 12th Week MRD≥10-3 group of children with significantly poor prognosis; multivariate analysis showed that the first 12 weeks of MRD≥10-3 as an independent adverse prognostic factors; 12 weeks of MRD <10-3 3-year EFS rate was ( 86.3 ± 4.1)%, and the 3-year EFS rate of MRD≥10-3 was (55.8 ± 9.1)%, the difference was statistically significant (P0.05); ③ MRD was negative on the 33rd day of chemotherapy Of the 98 children (relapse rate was 8.2%). Of the 98 children, 39 were positive at the 12th week (MRD ≥10-4), and 5 of them relapsed. At the Three of the 59 patients who were still negative for MRD at Week 12 relapsed. Of 108 MRD-positive children on Day 33, 19 relapsed (a relapse rate of 17.6%), with a relapse rate of MRD positive and negative Between poor There was statistically significant (P <0.05). Conclusion: The dynamic monitoring of MRD by flow cytometry in the treatment of children with B-ALL can effectively evaluate the therapeutic response, predict the prognosis, predict the recurrence and guide the chemotherapy regimen adjustment. Among them, the 15th, the 33rd and the 12th week MRD were 10-2,10-3,10-3 to distinguish the best risk for the cutoff, the first 12 weeks of MRD ≥ 10-3 for the independent adverse prognostic factors.