急性B型淋巴细胞白血病患儿免疫球蛋白、补体改变及诱导化疗后微小残留病灶对预后的影响

The influence of immunoglobulin, complement alterations and minimal residual disease after induction chemotherapy on the prognosis of children with acute B-cell lymphoblastic leukemia

摘要:

目的 探讨急性B型淋巴细胞白血病（BALL）患儿免疫球蛋白、补体改变及诱导化疗后微小残留病灶（MRD）对预后的影响。方法 选取徐州医科大学附属医院2019年7月—2021年7月行诱导化疗治疗的108例BALL患儿为研究对象。治疗前采用免疫比浊法检测免疫球蛋白、补体，治疗过程中和治疗结束时分别采用流式细胞仪检测骨髓MRD。通过电话或上门随访统计预后，以患儿死亡或随访截止时间（2023年3月30日）为随访终点，将死亡患儿纳入A组，存活患儿纳入B组。采用多因素一般Logistic回归模型分析影响BALL患儿预后的因素。绘制受试者工作特征（ROC）曲线分析以上影响因素预测BALL患儿预后的价值。结果 随访20～44个月，中位随访时间32个月。随访期间，12例患儿主动退出，7例患儿因家庭住址更换失去联系，其余89例患儿的死亡率为20.22%（18/89）。A组补体C3、免疫球蛋白M（IgM）、FMS样酪氨酸激酶3配体（Flt3L）水平均低于B组（P <0.05）。治疗结束后A组MRD阳性率、危险度高危层、血管性血友病因子（vWF）水平均高于B组（P <0.05）。多因素一般Logistic回归分析结果显示：危险度分层高危［O^R =7.629（95% CI：2.608，22.321）］、治疗结束后MRD阳性［O^R =8.508（95% CI：2.908，24.892）］、vWF水平高［O^R =1.302（95% CI：1.122，1.510）］均是BALL患儿死亡的危险因素（P <0.05）；补体C3水平低［O^R =0.516（95% CI：0.176，0.854）］、IgM水平低［O^R =0.596（95% CI：0.204，0.906）］、Flt3L水平低［O^R =0.805（95% CI：0.721，0.897）］均是BALL患儿死亡的保护因素（P <0.05）。ROC曲线分析结果显示：IgM、补体C3、危险度分层高危、治疗结束后MRD阳性、vWF、Flt3L及联合预测BALL患儿死亡的敏感性分别为77.8%（95% CI：0.676，0.880）、77.8%（95% CI：0.676，0.880）、72.2%（95% CI：0.620，0.824）、72.2%（95% CI：0.620，0.824）、76.7%（95% CI：0.665，0.869）、80.0%（95% CI：0.698，0.902）、94.4%（95% CI：0.842，1.000）；特异性分别83.1%（95% CI：0.729，0.933）、80.3%（95% CI：0.701，0.905）、78.9%（95% CI：0.687，0.891）、74.7%（95% CI：0.645，0.849）、80.0%（95% CI：0.698，0.902）、53.3%（95% CI：0.431，0.635）、93.0%（95% CI：0.828，1.000）；曲线下面积分别为0.818（95% CI：0.706，0.929）、0.803（95% CI：0.687，0.919）、0.750（95% CI：0.622，0.878）、0.733（95% CI：0.603，0.864）、0.777（95% CI：0.661，0.894）、0.799（95% CI：0.688，0.910）、0.925（95% CI：0.842，1.000）。结论 IgM、补体C3、危险度分层高危、治疗结束后MRD阳性、vWF、Flt3L联合预测BALL患儿死亡具有较高的价值。

Abstract:

Objective To explore the effects of immunoglobulin, complement changes and minimal residual disease (MRD) after induction chemotherapy on the prognosis of children with acute B-cell lymphoblastic leukemia (BALL).Methods A total of 108 children with BALL who underwent induction chemotherapy in the Affiliated Hospital of Xuzhou Medical University from July 2019 to July 2021 were selected as the research subjects. Immunoglobulin and complement were detected by immunoturbidimetry before treatment, and bone marrow MRD during and at the end of treatment was detected by flow cytometry. The prognosis of children with BALL was statistically analyzed through telephone or home visits. With the death of the children or the end date of follow-up (March 30, 2023) as the follow-up endpoint, the deceased children were included in Group A and the surviving children in group B. The factors influencing the prognosis of children with BALL were analyzed, and the ROC curve was used to analyze the value of predicting the prognosis of children with BALL.Results As of the follow-up date, the follow-up period ranged from 20 to 44 months, with a median follow-up period of 32 months. During the follow-up period, 12 children voluntarily withdrew, 7 children lost contact due to the change of home address, and among the remaining 89 children, the mortality rate was 20.22% (18/89). The levels of complement C3, IgM and Flt3L in group A were all lower than those in group B (P < 0.05). After the treatment, the positive rate of MRD, the high-risk layer of risk stratification and the level of vWF in group A were all higher than those in group B (P < 0.05). Multivariate Logistic regression analysis showed that the risk stratification was high-risk [O^R = 7.629 (95% CI: 2.608, 22.321) ] and positive MRD at the end of treatment [O^R = 8.508 (95% CI: 2.908, 24.892) ] and high vWF level [O^R = 1.302 (95% CI: 1.122, 1.510) ] were risk factors for death in children with BALL (P < 0.05); Low complement C3 level [O^R = 0.516 (95% CI: 0.176, 0.854) ], low IgM level [O^R = 0.596 (95% CI: 0.204, 0.906) ] and low Flt3L level [O^R = 0.805 (95% CI: 0.721, 0.897) ] were protective factors for the death of children with BALL (P < 0.05). Through ROC curve analysis, the sensitivities of IgM, complement C3, high-risk risk stratification, positive MRD after treatment, vWF, Flt3L, and combined prediction of death in children with BALL were 77.8% (95% CI: 0.676, 0.880), 77.8% (95% CI: 0.676, 0.880), 72.2% (95% CI: 0.620, 0.824), 72.2% (95% CI: 0.620, 0.824), 76.7% (95% CI: 0.665, 0.869), 80.0% (95% CI: 0.698, 0.902), 94.4% (95% CI: 0.842, 1.000); The specificities were 83.1% (95% CI: 0.729, 0.933), 80.3% (95% CI: 0.701, 0.905), 78.9% (95% CI: 0.687, 0.891), 74.7% (95% CI: 0.645, 0.849), 80.0% (95% CI: 0.698, 0.902), 53.3% (95% CI: 0.431, 0.635), 93.0% (95% CI: 0.828, 1.000); area under the curve were 0.818（95% CI：0.706, 0.929）、0.803（95% CI：0.687, 0.919）、0.750（95% CI：0.622, 0.878）、0.733（95% CI：0.603, 0.864）、0.777（95% CI：0.661, 0.894）、0.799（95% CI：0.688, 0.910）、0.925（95% CI：0.842, 1.000）.Conclusions The combined prediction of IgM, complement C3, risk stratification, positive MRD after treatment, vWF, and Flt3L has a relatively high value in predicting the death of children with BALL.