系统性炎症指标评估儿童淋巴瘤自体外周血干细胞移植术后生存的价值

Value of systemic inflammatory markers in evaluating the survival of children with lymphoma after autologous peripheral blood stem cells transplantation

目的探讨系统性炎症指标在评估儿童淋巴瘤自体外周血干细胞移植(APBSCT)术后生存情况中的价值。方法回顾性分析2013年1月至2017年6月在新疆医科大学第一附属医院接受APBSCT术治疗的56例儿童淋巴瘤患儿的临床资料,通过中性粒细胞与淋巴细胞比值(NLR)预测儿童淋巴瘤患儿APBSCT术后生存情况的ROC曲线,获得NLR的最佳诊断截点,并以NLR最佳诊断截点将患儿分为NLR≥2.25组(38例)与NLR<2.25组(18例),采用Kaplan-Meier生存曲线分析方法,比较两组患儿术后疾病无进展生存率和总生存率。结果56例儿童淋巴瘤患儿APBSCT术后1年、3年、5年的疾病无进展生存率分别为91.07%、71.43%、67.85%,术后1年、3年、5年的总生存率分别为94.64%、83.93%、71.43%。多因素Cox分析显示,临床分期、淋巴瘤国际预后评分(IPI)、移植前状态、NLR均为淋巴瘤患儿APBSCT术后疾病进展和死亡的独立预测因素。临床分期Ⅲ~Ⅳ期淋巴瘤患儿术后5年内疾病进展的风险是临床分期Ⅰ~Ⅱ期的2.124倍(95%CI:1.691~2.688,P=0.021),临床分期Ⅲ~Ⅳ期患儿术后5年内死亡的风险是临床分期Ⅰ~Ⅱ期的1.754倍(95%CI:1.333~2.234,P=0.025);IPI评分>2分淋巴瘤患儿术后5年内疾病进展的风险是IPI评分≤2分的2.322倍(95%CI:1.783~3.234,P=0.017),IPI评分>2分患儿术后5年内死亡的风险是IPI评分≤2分的1.654倍(95%CI:1.122~2.426,P=0.023);移植前病情部分缓解淋巴瘤患儿术后5年内疾病进展的风险是移植前病情完全缓解的2.423倍(95%CI:1.822~3.183,P=0.009),移植前病情部分缓解患儿术后5年内死亡的风险是移植前病情完全缓解的2.063倍(95%CI:1.765~2.885,P=0.010);移植前NLR每增加1个单位,淋巴瘤患儿术后5年内疾病进展的风险增加0.785倍(95%CI:1.244~2.256,P=0.041),移植前NLR每增加1个单位,患儿术后5年内死亡的风险增加0.571倍(95%CI:1.144~2.083,P=0.046)。以NLR值为2.25作为最佳诊断截点预测儿童淋巴瘤患儿APBSCT术后生存情况的灵敏度和特异度分别为81.34%和76.61%。Kaplan-Meier生存曲线分析显示,NLR≥2.25组淋巴瘤患儿术后1年、3年、5年的疾病无进展生存率分别为86.84%、63.18%、60.53%,均显著低于NLR<2.25组的100.00%、88.89%、83.33%,两组比较差异均有统计学意义(χ^(2)值分别为3.879、4.566、5.237,P<0.05);NLR≥2.25组患儿术后1年、3年、5年的总生存率分别为92.11%、76.32%、63.18%,均显著低于NLR<2.25组的100.00%、100.00%、88.89%,两组比较差异均有统计学意义(χ^(2)值分别为3.987、4.562、5.798,P<0.05)。结论移植前NLR可用于预测淋巴瘤患儿APBSCT术后的生存情况,移植前NLR≥2.25提示患儿术后复发率高,生存率较低,预后较差。

Objective To explore the value of systemic inflammatory markers in evaluating the survival of children with lymphoma after autologous peripheral blood stem cell transplantation(APBSCT).Methods The clinical data of 56 children with lymphoma who underwent APBSCT in the First Affiliated Hospital of Xinjiang Medical University from January 2013 to June 2017 were retrospectively analyzed,the receiver operating characteristic(ROC)curve for predicting the survival of children with lymphoma after APBSCT was obtained by neutrophil lymphocyte ratio(NLR),and the best diagnostic cut-off point of NLR was obtained.Based on the best diagnostic cut-off point of NLR,the children were divided into NLR≥2.25 group(38 cases)and NLR<2.25 group(18 cases),Kaplan Meier survival curve analysis was used to compare the progression free survival rate and overall survival rate between the two groups.Results The 1-year,3-year and 5-year progression free survival rates of 56 children with lymphoma after APBSCT were 91.07%,71.43%and 67.85%,respectively,the 1-year,3-year and 5-year overall survival rates were 94.64%,83.93%and 71.43%,respectively.Multivariate Cox analysis showed that clinical stage,lymphoma international prognostic index(IPI),pre transplant status,and NLR were independent predictors of progression and death in children with lymphoma after APBSCT.The children with clinical stageⅢ-Ⅳlymphoma had 2.124 times higher risk of disease progression within 5 years after operation than that in clinical stageⅠ-Ⅱ(95%CI:1.691-2.688,P=0.021),the children with clinical stageⅢ-Ⅳlymphoma had 1.754 times higher risk of death within 5 years after operation than that in clinical stageⅠ-Ⅱ(95%CI:1.333-2.234,P=0.025);the children with IPI score>2 had 2.322 times higher risk of disease progression within 5 years after operation than that with IPI score≤2(95%CI:1.783-3.234,P=0.017),and the children with IPI score>2 had 1.654 times higher risk of death within 5 years after operation than that with IPI score≤2(95%CI:1.122-2.426,P=0.023);The children with unresponsive disease before transplantation had 2.423 times higher risk of disease progression within 5 years after transplantation than that in children with remission before transplantation(95%CI:1.822-3.183,P=0.009),and the children with unresponsive disease before transplantation had 2.063 times higher risk of death within 5 years after transplantation than that in children with remission before transplantation(95%CI:1.765-2.885,P=0.010);For each unit increase of NLR before transplantation,the risk of disease progression within 5 years after operation increased 0.785 times(95%CI:1.244-2.256,P=0.041).For each unit increase of NLR before transplantation,the risk of death within 5 years after operation increased 0.571 times(95%CI:1.144-2.083,P=0.046).The sensitivity and specificity of using NLR value of 2.25 as the best diagnostic cut-off point to predict the postoperative survival of APBSCT in children with lymphoma were 81.34%and 76.61%,respectively.Kaplan Meier survival analysis showed that the 1-year,3-year and 5-year disease progression free survival rates of children in NLR≥2.25 group were 86.84%,63.18%and 60.53%,respectively,which were significantly lower than 100.00%,88.89%and 83.33%in NLR<2.25 group(χ^(2)=3.879,4.566 and 5.237,respectively,P<0.05);the overall survival rates at 1-year,3-years and 5-year in the NLR≥2.25 group were 92.11%,76.32%and 63.18%,respectively,which were significantly lower than 100.00%,100.00%and 88.89%in the NLR<2.25 group(χ^(2)=3.987,4.562 and 5.798,respectively,P<0.05).Conclusion NLR before transplantation can be used to predict the survival of children with lymphoma after APBSCT.NLR≥2.25 before transplantation indicates that the recurrence rate is high,the survival rate is low,and the prognosis is poor.