儿童急性B系淋巴细胞性白血病有效抗原组合及其临床应用探讨

Application of effective antigen combinations in childhood B lineage acute lymphoblastic leukemia

目的探讨使用流式细胞术（FCM）检测儿童急性B系淋巴细胞性白血病（B—lineage acute lymphoblastic leukemia，B-ALL）各有效抗原组合的发生频率及其与临床预后因素相关性。方法对289例初发B—ALL患儿的骨髓标本进行每组4个抗原，共9个抗原组合检测，统计各有效抗原组合的发生频率并与国外报告进行比较，分析各抗原组合在临床预后因素分组中的分布差异。结果（1）327例初发B-ALL患儿中，289例存在至少1组可用于微小残留病（minimal residual disease，MRD）检测的有效抗原组合，其覆盖率为88．4％。（2）不同有效抗原组合的发生频率不同，以TdT组频率最高，为70．59％。（3）部分有效抗原组合与临床表型以及治疗反应相关，CD58组和TdT组与良好预后因素相关，而CI）66c组和CD38组与不良预后因素相关。结论B—ALL不同有效抗原组合的发生频率不同，在中国患儿中的表达与国外报道有差异。TdT组有高表达频率，可作为简化的MRD检测目标组合。发生频率较高的4个抗原组合可以为无初发时MRD记录的患儿的疗效评估和治疗强度调整提供一定的参考依据。部分有效抗原组合对临床预后产生影响，可能为B—ALL的个体化治疗提供参考依据。

Objective To probe into the occurrence rates of the effective antigen combinations which were used to detect the minimal residual disease （MRD） by flow cytometry in childhood B-lineage acute lymphoblastic leukemia （B-ALL）, as well as the relationship between clinical-biologic factors and different combinations. Methods Among the 327 B-ALL children enrolled in our study, 289 cases were identified with at least one antigen combination as MRD marker. Their bone marrow samples were monitored by using 9 combinations with 4 antigens each, analyzed the occurrence rates and compared them with international reports. Also the differences in the distribution of each antibody combination in the different clinical-biologic groups were compared by the chi-square test and Fisher＇s exact test. Results （1） Totally 327 cases of childhood B-ALL were screened for antibody combinations of interest and 88.4 percent of them （289 cases） were identified with effective antibody combinations. （2） The occurrence frequencies of antigen combinations were different. The highest frequency was seen with TdT/CD10/CD34/CD19 combination which was 70. 59 percent. Expressions of antigen combinations in Chinese children were different from those in western countries. （ 3 ） Some antibody combinations presented different frequency among different clinical groups. CD38/CD10/CD34/CD19 was expressed more often in samples of relapsed patients （ P = 0. 045 ）. CD66c/CD10/CD3d/CD19 expression was significantly higher in BCR/ABL positive group （P = 0. 037） and relapsed patients group （P = 0. 047 ）. TdT/CD10/CD34/CD19 was expressed more in MLL-AF4 negative group （P = 0. 005） and Prednisone Good Response group （P = 0. 002）. CD58/CD10/CD34/CD19 was correlated with low relapse rate （ P = 0. 032）. Conclusion （ 1 ） The coverage rate of 9 antigen combinations in our study was 88.4%. The occurrences of frequency of different antibody combinations in B-ALL were different, and also different from that of western countries. The occurrence frequencies of antibody combinations CD21/CD10/CD34/CD19, CD22/CD10/CD34/CD19, CD10/CD56/CD34/- CD19 and TdT/ Cu/CD54/CD19 were lower than those of the western report, while CD58/CD10/- CD54/CD19, CIM5/ CD19/CD10/CD34, CD58/CDlO/CD34/CD19 and CD66c/CD10/CD34/CD19 were similar to those of the reports from western countries. （2）TdT/CDlO/CD34/CD19 may work as a simplified method to detect MRD in Chinese population. （ 3 ） The occurrence frequency of CD38/CD10/CD34/CD19, CIM5/CD19/CD10/ CD34, CD58/CD10/CD34/CD19, TdT/CD10/CD34/CD19 could be effective remediation and evidence to evaluate the remission quality and guide the therapy, especially for those with no original MRD marker record. （4）CD58/CD10/CD34/CD19 and TdT/CD10/CD34/CD19 may correlate with good prognosis, but CD66c/CDlO/CD34/CD19 and CD38/CD10/CD34/CD19 may predict poor prognosis. These results might contribute to individual risk evaluation and guide the therapy selection.