儿童急性B淋巴细胞白血病诱导治疗第8天外周血微小残留病的临床意义

Clinical significance of peripheral blood minimal residual disease detection at the eighth day of induction therapy in children with B-cell acute lymphoblastic leukemia

  • 摘要:
    目的 基于TARGET数据库分析诱导治疗第8天外周血微小残留病(MRD)检测在急性B淋巴细胞白血病(B-ALL)患儿预后评估中的临床意义。
    方法 下载TARGET数据库中2000—2010年诱导治疗第8天外周血MRD和第29天骨髓MRD资料完整的359例B-ALL患儿的数据。采用Spearman相关分析法探讨第8天外周血MRD与同期骨髓细胞形态学的相关性。采用Kaplan-Meier曲线分析第8天外周血MRD与无事件生存(EFS)的关系, 并分析第8天外周血MRD联合第29天骨髓MRD与EFS率的关系。采用Cox回归分析探讨B-ALL患儿预后的危险因素。
    结果 Spearman相关分析显示,第8天外周血MRD与同期骨髓原始细胞占比呈正相关(r=0.620, P < 0.001)。生存曲线显示,第8天外周血MRD < 0.01%、0.01%~ < 0.10%、0.10%~ < 1.00%、≥1.00%患儿的5年EFS率比较,差异有统计学意义(P < 0.001)。第8天外周血MRD与第29天骨髓MRD检测结果双阴性者预后最佳,单阳性者次之,双阳性者预后最差,差异有统计学意义(P < 0.001)。第29天骨髓MRD阴性患儿中,第8天外周血MRD阴性者的5年EFS率高于第8天外周血MRD阳性者,差异有统计学意义(P=0.009)。Cox回归分析显示,第8天外周血MRD≥0.10%(HR=1.967, 95%CI为1.234~3.134, P=0.004)、第29天骨髓MRD≥0.01%(HR=2.076, 95%CI为1.423~3.027, P < 0.001)均为B-ALL患儿EFS的独立危险因素。
    结论 诱导治疗第8天外周血MRD在儿童B-ALL预后评估中具有重要的临床意义,可作为第29天骨髓MRD的强有力补充。

     

    Abstract:
    Objective To analyze clinical significance of peripheral blood minimal residual disease (MRD) detection at the eighth day of induction therapy in evaluating prognosis of children with B-cell acute lymphoblastic leukemia (B-ALL) based on the TARGET database.
    Methods Data of 359 B-ALL children with peripheral blood MRD at the eighth day of induction therapy and bone marrow MRD at 29th day of induction therapy from year 2000 to 2010 were downloaded from TARGET database. Spearman correlation analysis was used to explore the association between peripheral blood MRD at the eighth day and morphology of bone marrow cells in the same period. Kaplan-Meier curve was used to analyze the relationship between peripheral blood MRD at the eighth day and event free survival (EFS), and further analyze the relationship of combined detection of peripheral blood MRD at the eighth day and bone marrow MRD at 29th day with EFS. Cox regression model was used to analyze the risk factors for prognosis in B-ALL children.
    Results Spearman correlation analysis showed that the level of peripheral blood MRD at the eighth day was positively correlated with the proportion of bone marrow blasts at day 8 (r=0.620, P < 0.001). Survival analysis showed that there were significant differences in 5-year EFS rates of MRD < 0.01%, 0.01% to 0.10%, 0.10% to 1.00% and ≥ 1.00% in peripheral blood at the eighth day(P < 0.001). Double-negative patients with peripheral blood MRD at the 8th day and bone marrow MRD at the 29th day had the best prognosis, followed by single-positive patients, and double-positive patients had the worst prognosis, the differences were statistically significant (P < 0.001). The combined MRD at both time points showed that the prognosis was best in the double-negative group, followed by the single-positive group and worst in the double-positive group (P < 0.001). In children with negative bone marrow MRD at day 29, the 5-year EFS rate of children negative for MRD in peripheral blood at the eighth day was significantly higher than those positive for MRD in peripheral blood at the eighth day(P=0.009). Cox regression analysis showed that MRD ≥ 0.10% in peripheral blood on day 8(HR=1.967; 95%CI, 1.234 to 3.134; P=0.004), MRD ≥ 0.01% in bone marrow on day 29 (HR=2.076; 95%CI, 1.423 to 3.027; P < 0.001) were independent risk factors for EFS in B-ALL children.
    Conclusion Peripheral blood MRD at day 8 of induction therapy has important clinical significance in prognosis assessment in children with B-ALL, and can be used as a strong supplement for the prognosis assessment of B-ALL children with bone marrow MRD at day 29.

     

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