初治与复发B细胞急性淋巴细胞白血病患者白血病相关免疫表型的比较

目的比较初治和复发时B细胞急性淋巴细胞白血病（B-ALL）的白血病相关免疫表型（LAIP）特点,探讨其对微量残留病（MRD）监测的影响.方法标记4～6组四色抗体组合,利用多参数流式细胞术（FCM）以CD45/SSC设门对410例初治和6例复发的B-ALL患者进行免疫分型检测.并采用CD34/CD10/CD45/CD19为主的2种四色荧光标记抗体组合,对98例B-ALL患者进行多参数FCM MRD检测.结果与初治B-ALL患者相比,复发患者中CD45异常表达者明显增多,分别为37.8%和69.2%（P=0.000）.通过对15例初治和复发患者的配对样本分析,9例患者（包括8例骨髓复发,1例中枢神经系统复发）出现免疫标志变化,其中4例患者CD45表达减弱,2例增强;4例患者CD34表达减弱;2例患者CD10表达增强,而CD19较稳定.对7例骨髓复发患者进行了MRD随访检测,均在复发前的2～4个月发现MRD,并且表型与复发后一致.结论较高比例的复发患者出现免疫表型变化,这种改变在复发前的MRD状态时已经出现,但不影响MRD监测的准确性.

Comparison of the immunophenotype of patients with B lineage acute lymphoblastic leukemia at diagnosis and relapse

Objective To compare the leukemia-associated immunophenotypes (LAIP) in patients with B lineage acute lymphoblastic leukemia(B-ALL) at diagnosis and relapse,and investigate its implica- tions for minimal residual disease (MRD) detection.Methods The immunophenotype of leukemia cells from 410 newly diagnosed and 6 relapsed patients with B-ALL were detected by four to six antibody combina- tion,mainly CD34/CD10/CD45/CD19 of 4-color CD45/SSC gating flow cytometry (FCM).Results The proportion of CD45 under-expressed or negative in relapsed patients was much higher than that in newly diag- nosed patients,being 69.2% and 37.8% respectively.Immunophenotypic changes occurred in 9 relapsed patients (including 8 hematological relapse and 1 centrl nerves system relapse) when analyzed by paired samples analysis at diagnosis vs at relapse:4 cases showed CD45 downmodulation and 2 upmodulation;4 CD34 downmodulation and 2 CD10 upmodulation,while the expression of CD19 remained no change.MRD was observed in all 7 cases of hematological relapse 2-4 months before relapse,and the immunophenotype of MRD cells was the same as that in relapse.Conclusion A high frequency of immunophenotypic changes oc- curred at relapse and even in MRD before relapse,however the accuracy of MRD monitoring seemed not af- fected by the FCM strategy used in this investigation.