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[流式细胞术检测儿童急性B淋巴细胞白血病微小残留病的临床意义]

[The clinical significance of detecting minimal residual disease in acute childhood B-cell lymphoblastic leukemia with flow cytometry].

作者信息

Zhang Le-ping, Cheng Yi-fei, Liu Gui-lan, Lu Ai-dong, Liu Yan-rong, Wang Hui

机构信息

Department of Pediatrics, Peking University People's Hospital, Beijing 100044, China.

出版信息

Zhonghua Er Ke Za Zhi. 2005 Jul;43(7):481-5.

PMID:16083543
Abstract

OBJECTIVE

Flow cytometry may be used to detect minimal residual disease (MRD) in acute lymphoblastic leukemia because leukemic cells often display aberrant phenotypes when compared to normal cells. The present study was designed to establish a flow cytometric method for detecting MRD in children with B-ALL and evaluate its clinical prognostic value. The investigators also aimed to study the value of the detection of MRD by flow cytometry in childhood B-ALL without effective antibody combinations.

METHODS

Thirty-six cases of childhood B-ALL with effective antibody combinations were performed MRD analysis after induction therapy. The authors detected MRD in 6 cases without effective antibody combinations by the four-color antibody combinations consisting of CD(45)/CD(19)/CD(10)/CD(34) and CD(45)/CD(19)/CD(20)/CD(22) and detected the aberrance of the minor subsets of CD(19)(+) cells.

RESULTS

(1) Forty-two cases of childhood B-ALL were screened for antibody combinations of interest and were identified in 86% (36/42) of the cases. The sensitivity of this method was 0.01%. (2) Patients with MRD levels > or = 0.01% at 9 and 12 months of therapy had significantly low disease-free survival compared with patients with MRD levels < 0.01%. (3) Six out of seven patients with recurrence in the BM had MRD levels > or = 0.1% prior to recurrence. Patients with MRD levels > or = 0.1% during chemotherapy had significantly low disease-free survival as compared with patients with MRD values < 0.1%. (4) Two out of seven patients with recurrence had positive results of the qualitative PCR prior to recurrence. (5) Five patients with recurrence had no shift of antigen expression at relapse except that a patient missed CD(13). (6) Detectable MRD was not found in six patients without effective antibody combinations.

CONCLUSION

(1) Flow cytometry is a sensitive and specific method for detecting MRD of childhood ALL, and could predict the coming relapse. (2) Patients with MRD levels > 10(-3) had poor prognosis. (3) The levels of MRD at month 9 and 12 had prognostic value. (4) The value of antibody combinations consisting of CD(45)/CD(19)/CD(10)/CD(34) and CD(45)/CD(19)/CD(20)/CD(22) should be further investigated in patients without effective antibody combinations.

摘要

目的

流式细胞术可用于检测急性淋巴细胞白血病中的微小残留病(MRD),因为与正常细胞相比,白血病细胞常表现出异常表型。本研究旨在建立一种检测儿童B-急性淋巴细胞白血病(B-ALL)中MRD的流式细胞术方法,并评估其临床预后价值。研究者还旨在研究在没有有效抗体组合的儿童B-ALL中,通过流式细胞术检测MRD的价值。

方法

对36例有有效抗体组合的儿童B-ALL病例在诱导治疗后进行MRD分析。作者通过由CD(45)/CD(19)/CD(10)/CD(34)和CD(45)/CD(19)/CD(20)/CD(22)组成的四色抗体组合,对6例没有有效抗体组合的病例检测MRD,并检测CD(19)(+)细胞微小亚群的异常情况。

结果

(1) 对42例儿童B-ALL病例筛查感兴趣的抗体组合,86%(36/42)的病例被鉴定出来。该方法的灵敏度为0.01%。(2) 治疗9个月和12个月时MRD水平≥0.01%的患者与MRD水平<0.01%的患者相比,无病生存率显著降低。(3) 7例骨髓复发患者中有6例在复发前MRD水平≥0.1%。化疗期间MRD水平≥0.1%的患者与MRD值<0.1%的患者相比,无病生存率显著降低。(4) 7例复发患者中有2例在复发前定性PCR结果为阳性。(5) 5例复发患者在复发时除1例缺失CD(13)外,抗原表达无变化。(6) 6例没有有效抗体组合的患者未检测到可检测的MRD。

结论

(1) 流式细胞术是检测儿童ALL中MRD的一种敏感且特异的方法,可预测即将到来的复发。(2) MRD水平>10(-3)的患者预后较差。(3) 第9个月和第12个月时的MRD水平具有预后价值。(4) 对于没有有效抗体组合的患者,由CD(45)/CD(19)/CD(10)/CD(34)和CD(45)/CD(19)/CD(20)/CD(22)组成的抗体组合的价值应进一步研究。

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