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目的研究使用流式细胞术检测小儿急性B淋巴细胞白血病(acutelymphoblasticleukemia,ALL)微小残留病(minimalresidualdisease,MRD)的临床预后价值。方法能将残留白血病细胞与正常骨髓细胞区分开来的抗体组合称为有效抗体组合。我们使用流式细胞术对36例具有有效抗体组合的BALL患儿缓解后的骨髓标本进行MRD的定期检测。对6例无有效抗体组合的患儿,我们使用CD45/CD19/CD34/CD10与CD45/CD19/CD20/CD22两个抗体组合定期检测骨髓标本。结果(1)在42例患儿中有36例(86%)具有有效抗体组合;(2)在治疗6个月时间点时,MRD水平≥10-4的患儿(13例)无病生存率(diseasefreesurvival,DFS)与MRD水平<10-4的患儿(12例)相比无统计学意义(P=0.62);在治疗9个月时,MRD水平≥10-4的患儿(10例)要比MRD水平<10-4的患儿(13例)生存率低(P=0.025);在治疗12个月时,MRD水平≥10-4的患儿(8例)要比MRD水平<10-4的患儿(9例)生存率低(P=0.042);(3)共有7例患儿复发,其中6例复发患儿在复发前的4～10个月均检测到≥10-3水平的MRD。在随访过程中至少有1次MRD水平≥10-3患儿的无病生存率较MRD水平在10-3以下的患儿为低(P=0.003);(4)5例复发患儿的免疫表型基本未发生变化,只有1例丢失了CD13抗原;(5)在6例无有效抗体组合患儿中未发现有意义的MRD。结论(1)MRD水平在10-3或以上的患儿预后较差;(2)治疗9个月与12个月时间点的MRD水平有预后价值;(3)对于无有效抗体组合的患儿,CD45/CD19/CD34/CD10与CD45/CD19/CD20/CD22抗体组合的效果应进一步评估。
Objective To investigate the clinical prognostic value of flow cytometry in the detection of minimal residual disease (MRD) in children with acute lymphoblastic leukemia (ALL). Method The combination of antibodies that distinguish residual leukemia cells from normal bone marrow cells is referred to as an effective antibody combination. We used flow cytometry to routinely detect MRD in bone marrow samples from 36 BALL children with valid antibody combinations. For 6 children with no valid combination of antibodies, we used a combination of two antibodies, CD45 / CD19 / CD34 / CD10 and CD45 / CD19 / CD20 / CD22, to periodically detect bone marrow samples. Results (1) 36 (86%) of 42 children had effective antibody combinations; (2) 13 children with MRD level ≥10-4 had no disease-free survival at the 6-month point of treatment There was no significant difference (P = 0.62) between diseasefreesurvival (DFS) and children with MRD level <10-4 (P = 0.62); at 9 months, children with MRD level≥10-4 Cases) had lower survival rates (P = 0.025) than those with MRD levels <10-4 (P = 0.025). At 12 months, children with MRD levels ≥10-4 (8 patients) had lower survival than those with MRD The survival rate of children younger than 10 years (9 cases) was low (P = 0.042). (3) A total of 7 children relapsed, of which 6 children relapsed from 4 to 10 months before recurrence were all detected ≥10 -3 level MRD. During the follow-up, the disease-free survival rate of children with MRD≥10-3 was lower than that of children with MRD level below 10-3 at least once (P = 0.003). (4) There was no change in the phenotype. Only 1 patient lost the CD13 antigen. (5) No significant MRD was found in 6 children without effective antibody combination. Conclusions (1) The prognosis of children with MRD level 10-3 or above is poor; (2) the prognosis value of MRD level at 9 and 12 months; (3) in children with no effective antibody combination , The combination of CD45 / CD19 / CD34 / CD10 with CD45 / CD19 / CD20 / CD22 antibodies should be further evaluated.