极限稀释法对急性淋巴细胞白血病IgH和Vδ2Dδ3基因重排的定量检测及其意义

Quantitative analysis of IgH and Vδ2Dδ3 gene rearrangement and its clinical significance in children with acute lymphoblastic leukemia by limiting dilution assay

目的 探讨急性淋巴细胞白血病 (ALL)IgH和Vδ2Dδ3基因重排微小残留病 (MRD)值在判断预后的意义。方法 运用极限稀释法对ALL完全缓解期 (CR)后不同时期的骨髓标本进行IgH和Vδ2Dδ3基因重排的定量检测。结果 2 4例初诊时存在IgH或Vδ2Dδ3基因重排的ALL患者CR后不同时期 5 1份骨髓标本中 ,MRD >0 .1%者 3例 ,其中 2例复发 ,1例失访 ,复发率为 75 %。MRD为 0 .0 0 2 %～ 0 .1%者 6例 ,1例复发 ,复发率为 17%。MRD <0 .0 0 2 %者 15例 ,无复发。复发组 3例MRD均值为 0 .2 39% ,未复发组 2 0例MRD均值为 0 .0 0 4%。复发组MRD明显高于未复发组 ,P<0 .0 5。结论 ALL时IgH和Vδ2Dδ3基因重排的定量检测的MRD增高 ,则病人的复发危险率随之增高。加强化疗后化疗药物对白血病细胞的杀伤效应使MRD减少 ,CR后MRD定期监测对指导化疗药物的选择、观察疗效。

Objective The purpose of this paper was to study the clinical significance of immunoglobulin heavy chain (IgH) gene and T cell recepter (TCR) V δ2D δ3 gene arrangement in the minimal residual disease (MRD) changes in children with acute lymphoblastic leukemia (ALL).Methods Quantitative analysis of IgH and V δ2D δ3 gene rearrangement in bone marrow samples of patients with ALL after complete remission (CR) was done by limiting dilution assey. Results MRD cells in bone marrow samples with ALL at CR and after in 24 cases were quantitated.MRD was more than 0.1 % in 3 cases.The disease relapsed in 2 cases of them and 1 of them lost following up.The relapse rate was 75 %. MRD was between 0.002 % and 0.1 % in 6 cases,The disease relapsed in 1 of them.The mean leavel of MRD decreased gradually to negative in the other.The relapse rate was 17 %.MRD was less than 0.002 % in 15 cases, no recurrence.The average amount of MRD was 0.239 % in relapse group (3 patients) and 0.004 % in nonrelapse group (20 patients) (P<0.05).Conclusion The higher amout of MRD increased,the higher the rate of relapse.After intensified chemotherapy,MRD was decreased by killing leukemia cells. Following up continuously MRD in ALL plays a guiding role in sellecting chemotherapy,observing curative effect and predicting prognosis.