急性B淋巴细胞白血病儿童化疗后微小残留病灶免疫表型改变的分析

Analysis of Immunophenotype Changes of Minimal Residual Disease in children with Acute B Lymphoblastic Leukemia after Chemotherapy

目的:分析儿童急性B淋巴细胞白血病(B-cell acute lymphoblastic leukemia,B-ALL)化疗过程中首次微小残留病灶(minimal residual disease,MRD)免疫表型的变化规律及特点,为临床诊断及后续微小残留病的监测提供依据。方法:回顾性分析我院2013年1月至2018年4月收治的393例B-ALL患儿的免疫分型结果及诱导化疗第15天首次MRD数据。结果:(1)在393例白血病中,B-ALL相关特征性免疫表型的出现频率为:CD19+/CD10+/34+64.4%;CD19+/CD10+/34部分表达,15.5%;CD19+/CD34+/CD20+,58.5%;CD19+/CD10+/CD13+,13.2%;CD19+/CD10+/CD33+,5.9%;CD19+/CD10+/CD117+,0.7%;CD19+/CD10+/CD123+,50.1%;CD19+/CD10-/34±,5.9%;CD19+/CD10-/CD20-,2.5%;CD34bright,12.2%;(2)共有285例首次MRD检测结果呈阳性,有181例(63.5%)MRD检测结果至少有1个抗原荧光强度发生改变,其中出现一个抗原强度变化的为83例(29.1%),2个抗原荧光强度变化的为57例(20.0%),3个抗原荧光强度变化为31例(10.9%),4个及4个以上抗原荧光强度变化为10例(3.5%)。抗原荧光强度变化频率最高的依次为CD45、CD34、CD20;(3)共有7例患儿复发,复发时行免疫分型检测,其中4例与初发时有抗原荧光强度变化。结论:(1)儿童B-ALL远高于其他白血病类型,且具有独特的相关特征性免疫表型。初发B-ALL免疫分型结果不仅可完善白血病MICM分型,更是化疗后MRD监测的线索及客观依据;(2)在儿童B-ALL化疗过程中,免疫表型极有可能会发生变化,在后续的微小残留病灶检测过程中应注意对变化抗原的判断和追踪。

Objective: To review the flow immunophenotype results of the frist minimal residual disease(minimal residual disease, MRD) of 393 children with B-cell acute lymphoblastic leukemia(B-ALL), and compare with the results of immunophenotyping at the initial diagnosis. Analyze the surface antigen changes occurring in the B-ALL chemotherapy phase of the MRD, in order to understand the feature and changing characteristics of children’s B-ALL immunophenotype and to provide evidence for clinical diagnosis and follow-up monitoring of MRD. Methods: A retrospective analysis of the immunophenotyping results and the first MRD data of induction chemotherapy for fifteenth days of 393 patients with B-ALL in our hospital from January 2013 to April 2018 was performed. Results:(1)in 393 cases of B-ALL, the frequency of leukaemia related immunophenotype(characterization of leukemia-associated immunotyping,LAIP) were: CD19+/CD10+/34+, 64.4 %;CD19+/CD10+/34 partial expression, 15.5 %;CD19+/CD34+/CD20+, 58.5 %;CD19+/CD10+/CD13+, 13.2 %;CD19+/CD10+/CD33+,5.9 %;CD10+/CD117+, 0.7 %;CD19+/CD10+/CD123+, 50.1 %;CD19+/CD10-/34+, 5.9 %;CD19+/CD10-/CD20-, 2.5 %;CD34 bright, 12.2 %;(2) A total of 285 first MRD tests were positive, 181(63.5 %) MRD detected at least 1 antigen fluorescence intensity changes, of which 1 antigen intensity change was 83 cases(29.1 %), 2 antigen fluorescence intensity changes were 57 cases(20 %), 3 antigen fluorescence intensity changes were 31 cases(10.9 %), 4 and more than 4 antigen fluorescence intensity changes were 10 cases(3.5 %). The highest frequency of antigen fluorescence intensity was CD45, CD34 and CD20.(3) A total of 7 children were recrudescence, of which 4 cases of antigen fluorescence intensity change compared with the initial stage. Conclusion:(1) children’s B-ALL is much higher than other types of leukemia, and has a unique characteristic phenotype. The results of initial B-ALL immunophenotype can not only improve the MICM classification of leukemia, but also provide clues and objective evidence for MRD monitoring after chemotherapy.(2) Immunophenotype changes are most likely to occur during B-ALL treatment in children, and careful judgment and tracking should be made in the subsequent detection process of MRD.