目的 探讨利妥昔单抗(RTX)治疗儿童频复发/激素依赖型肾病综合征(FRNS/SDNS)的疗效和安全性，以及影响疗效的因素。 方法 回顾性病例系列研究。收集2019年9月至2022年3月在郑州大学第一附属医院接受B细胞指导下RTX治疗(单次剂量375 mg/m2，最大500 mg，当外周血CD19＋B细胞≥0。01时追加1剂)的FRNS/SDNS患儿的临床资料，比较RTX治疗前后复发次数及激素累积剂量；Kaplan-Meier方法分析RTX治疗后无复发生存率和无FRNS/SDNS生存率。Cox比例风险回归模型分析复发的影响因素。 结果 纳入47例患儿，男35例，女12例；首次应用RTX年龄10。2(6。9，13。0)岁；既往使用1种免疫抑制剂33例，2种及以上14例；RTX治疗剂次3。0(2。0，3。0)次。RTX治疗后复发次数[0(0，0。55)次/年比1。62(1。09，2。40)次/年]和激素累积剂量[0。12(0。05，0。21) mg/(kg·d)比0。40(0。20，0。56) mg/(kg·d)]均较既往免疫抑制剂治疗时明显下降，差异均有统计学意义(Z＝－5。56、－5。54，均P<0。001)。RTX治疗后6、12、18、24个月无复发生存率分别为80。9%、72。3%、68。1%、68。1%，无FRNS/SDNS生存率分别为93。6%、89。4%、89。4%、89。4%。单因素Cox回归分析显示，既往免疫抑制剂治疗时的复发次数多是RTX治疗后复发的危险因素(P<0。05)。14例复发患儿中，6例发生在CD19＋B细胞<0。01时，RTX治疗后的复发次数显著高于CD19＋B淋巴细胞≥0。01时，差异有统计学意义(Z＝－2。84，P＝0。005)。RTX治疗及随访期间无严重不良反应发生。 结论 B细胞指导下RTX治疗儿童FRNS/SDNS有效且安全，既往免疫抑制剂治疗时的复发次数多是RTX治疗后复发的危险因素，B细胞耗竭状态时复发预示RTX治疗结局不良。 Objective To investigate the efficacy and safety of Rituximab (RTX) in the treatment of children with frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS) and to analyze the factors influencing the efficacy。 Methods Case series study。The clinical data of children with FRNS/SDNS who received B-cell-guided RTX (single dose: 375 mg/m2， maximum dose: 500 mg， one additional dose when peripheral blood CD19+ B lymphocytes ≥0。01) in the First Affiliated Hospital of Zhengzhou University from September 2019 to March 2022 were retrospectively collected。The frequency of relapse and cumulative dose of glucocorticoids before and after RTX treatment were compared。The Kaplan-Meier method was used to analyze relapse-free survival rate and FRNS/SDNS-free survival rate after RTX treatment。The influencing factors of relapse were analyzed using the Cox proportional hazards regression model。 Results Totally 47 children were enrolled， including 35 males and 12 females the age of first application of RTX was 10。2 (6。9， 13。0) years 33 children had used one type of immunosuppressant before， and 14 children had used two or more types of immunosuppressant before the dose of RTX treatment was 3。0 (2。0， 3。0)。 The frequency of relapse[0(0， 0。55) times/year vs。1。62 (1。09， 2。40) times/year] and cumulative dose of glucocorticoids[0。12 (0。05， 0。21) mg/(kg·d) vs。0。40 (0。20， 0。56) mg/(kg·d)] after RTX treatment significantly decreased compared with previous immunosuppressive treatment (Z=-5。56， -5。54， all P<0。001)。 The relapse-free survival rates at 6， 12， 18 and 24 months after treatment were 80。9%， 72。3%， 68。1% and 68。1%， respectively， and the FRNS/SDNS-free survival rates were 93。6%， 89。4%， 89。4% and 89。4%， respectively。Univariate Cox regression analysis showed that the high frequency of relapse during previous immunosuppressive therapy was a risk factor for relapse after RTX treatment (P<0。05)。 Of the 14 children who relapsed， 6 occurred in children whose CD19+ B lymphocytes<0。01， and the frequency of relapse after RTX treatment was significantly higher than those whose CD19+ B lymphocytes≥0。01 (Z=-2。84， P=0。005)。 No severe adverse reactions occurred during RTX treatment and follow-up。 Conclusions The B-cell-guided RTX is effective and safe in the treatment of FRNS/SDNS in children。The high frequency of relapse during previous immunosuppressive therapy is a risk factor for relapse after RTX treatment， and relapse in the state of B lymphocyte depletion predicts poor outcomes of RTX treatment。
Effect and influencing factors of Rituximab in the treatment of children with frequently relapsing/steroid-dependent nephrotic syndrome
Objective To investigate the efficacy and safety of Rituximab (RTX) in the treatment of children with frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS) and to analyze the factors influencing the efficacy. Methods Case series study.The clinical data of children with FRNS/SDNS who received B-cell-guided RTX (single dose: 375 mg/m2, maximum dose: 500 mg, one additional dose when peripheral blood CD19+ B lymphocytes ≥0.01) in the First Affiliated Hospital of Zhengzhou University from September 2019 to March 2022 were retrospectively collected.The frequency of relapse and cumulative dose of glucocorticoids before and after RTX treatment were compared.The Kaplan-Meier method was used to analyze relapse-free survival rate and FRNS/SDNS-free survival rate after RTX treatment.The influencing factors of relapse were analyzed using the Cox proportional hazards regression model. Results Totally 47 children were enrolled, including 35 males and 12 females the age of first application of RTX was 10.2 (6.9, 13.0) years 33 children had used one type of immunosuppressant before, and 14 children had used two or more types of immunosuppressant before the dose of RTX treatment was 3.0 (2.0, 3.0). The frequency of relapse[0(0, 0.55) times/year vs.1.62 (1.09, 2.40) times/year] and cumulative dose of glucocorticoids[0.12 (0.05, 0.21) mg/(kg·d) vs.0.40 (0.20, 0.56) mg/(kg·d)] after RTX treatment significantly decreased compared with previous immunosuppressive treatment (Z=-5.56, -5.54, all P<0.001). The relapse-free survival rates at 6, 12, 18 and 24 months after treatment were 80.9%, 72.3%, 68.1% and 68.1%, respectively, and the FRNS/SDNS-free survival rates were 93.6%, 89.4%, 89.4% and 89.4%, respectively.Univariate Cox regression analysis showed that the high frequency of relapse during previous immunosuppressive therapy was a risk factor for relapse after RTX treatment (P<0.05). Of the 14 children who relapsed, 6 occurred in children whose CD19+ B lymphocytes<0.01, and the frequency of relapse after RTX treatment was significantly higher than those whose CD19+ B lymphocytes≥0.01 (Z=-2.84, P=0.005). No severe adverse reactions occurred during RTX treatment and follow-up. Conclusions The B-cell-guided RTX is effective and safe in the treatment of FRNS/SDNS in children.The high frequency of relapse during previous immunosuppressive therapy is a risk factor for relapse after RTX treatment, and relapse in the state of B lymphocyte depletion predicts poor outcomes of RTX treatment.
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