儿童急性B淋巴细胞白血病患者诱导化疗后免疫表型的改变及其临床意义

Changes of immunophenotype in children with acute B lymphoblastic leukemia after induction chemotherapy and its clinical significance

目的探讨儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)诱导结束时白血病细胞抗原表达的变化情况及其对预后的影响。方法回顾性研究于2010年至2015年期间被诊断为B-ALL的691例儿童患者。患儿骨髓标本在初诊时进行白血病免疫分型检测,并在治疗第33天时进行微小残留病(minimal residual disease,MRD)检测。其中,155例MRD≥0.01%的患者被纳入本次研究。用四色单克隆荧光抗体组合通过多参数流式细胞术进行白血病细胞免疫表型变化的研究。结果 86例(55.5%)患者至少有一个抗原标志出现了表型转换,CD19是最稳定的标记。然而,将近1/3患儿的CD20在初诊和化疗第33天时表达有显著性差异。抗原表达的变化与无事件生存率(event-free survival,EFS)、无复发生存率(relapse-free survival,RFS)或总生存率(overall survival,OS)无显着相关(P>0.05)。多因素分析显示白细胞计数(white blood cell,WBC)和BCR-ABL在儿童ALL中具有独立的预后价值。结论虽然抗原表达的改变在诱导缓解治疗结束时很普遍,但是在化疗第33天MRD阳性的患者中,抗原表达的改变与预后价值无关。

ObjectiveTo investigate the changes in antigen expressions on leukemic cells and its effect on prognosis at the end of induction in children with acute lymphoblastic leukemia （ALL）. MethodsThe retrospective study included 691 children diagnosed with B-ALL between 2010 and 2015. The bone marrow specimens of the children were used for the detection of leukemia immunophenotype at the flrst diagnosis, and for the detection of minimal residual disease （MRD） at the 33rd day of treatment. Among them, 155 patients with MRD greater than 0.01% were included in this study. The immunophenotypic changes of leukemia cells were studied by using a four-color monoclonal fluorescent antibody combination through multi-parameter flow cytometry. Results86 of 155 （55.5%） cases showed phenotype shifts at least one marker. CD19 was the most stable markers. However, nearly one third of the children had signiflcant differences in CD20 expression on the 33rd day of initial diagnosis and chemotherapy. Changes in antigen expression were not significantly correlated with event-free survival （EFS）, relapse-free survival （RFS） or overall survival （OS） （P〉0.05）. Multivariate analysis showed that white blood cell （WBC） and BCR-ABL had independent prognostic value in ALL. ConclusionAlthough changes in antigen expression were common at the end of induction remission therapy, they were not associated with prognostic value in patients with MRD positive on day 33 of chemotherapy.