利妥昔单抗治疗儿童频繁复发型肾病综合征的远期观察

Long-term observation of Rituximab therapy for children with frequently relapsing nephrotic syndrome

目的观察利妥昔单抗(RTX)治疗儿童频繁复发型肾病综合征(FRNS)的远期疗效和不良反应,探讨RTX在儿童FRNS中的可行性治疗方案。方法回顾性分析2011年2月至2017年12月南方医科大学南京临床医学院金陵医院儿科接受RTX治疗[375 mg/(m^2·次),2~3次]的FRNS患儿临床资料,随访12~36个月,观察患儿年龄、性别、复发次数、激素和免疫抑制剂的使用剂量、不良反应及实验室指标(如外周血CD20^+B淋巴细胞计数、24 h尿蛋白定量)。结果入选34例(男23例,女11例),RTX首次治疗中位年龄为6(2~12)岁。第1次治疗,完全缓解34例(100%,34/34例),12例(35%,12/34例)随访中复发,RTX治疗前复发次数为(2.94±1.08)次,治疗后复发次数为(0.27±0.45)次,二者比较差异有统计学意义(t=11.9,P<0.05)。第2次治疗,前6个月,3例因"感染"复发,余无不适;后6个月,23例中5例(21.7%,5/23例)复发1次,11例情况不明。2次治疗间隔时间<12个月者复发2例(12.5%,2/16例),间隔时间≥12个月者复发10例(55.5%,10/18例)。第3次治疗,间隔6~15个月,15例中1例(6.67%)复发,余病情稳定。另外,20例FRNS患儿经RTX首次治疗,治疗前6个月激素累积剂量[(2.50±0.87) g ]与治疗后6个月激素累积剂量[(1.30±0.97) g ]比较,差异有统计学意义(t=6.05,P=0.001),其中15例他克莫司治疗前(1.62±0.77) mg/24 h,治疗6~12个月后降至(0.62±0.96) mg/24 h,差异有统计学意义(t=6.80,P=0.000)。2例首次用药时出现胸闷、心悸、恶心、呕吐、头晕、头痛,3例出现轻微上呼吸道感染,1例肺部较严重感染。结论远期随访RTX治疗儿童FRNS是安全有效的。

Objective To observe the long-term efficacy and adverse reactions of Rituximab (RTX) in the treatment of children with frequently relapsing nephrotic syndrome (FRNS), and to explore the feasible treatment plan of RTX in children with FRNS. Methods FRNS children with RTX[375 mg/(m^2·time), 2-3 times] from Department of Pediatrics, Jinling Hospital, Nanjing Clinical School of Southern Medical University between February 2011 and December 2017 were retrospectively reviewed, and followed up for 12-36 months.Age, gender, number of relapses, dose of steroids and immunosuppressants, adverse reactions and laboratory indicators(peripheral blood CD20^+ B lymphocyte count, 24-hour urine protein quantification, etc) were observed. Results Thirty-four patients(23 males and 11 females) with FRNS were included in the present study, and the median age for the first RTX treatment was 6 years (2-12 years). After the first treatment, there was complete remission in 34 patients (100%, 34/34 cases), and 12 patients (35%, 12/34 cases) relapsed during follow-up.The number of relapse after treatment[(0.27±0.45) times]significantly decreased compared with that before treatment[(2.94±1.08) times;t=11.9, P<0.05]. After the second treatment, 3 children relapsed due to " infection" and no discomfort was found in the first 6 months;5 of 23 cases (21.7%, 5/23 cases) relapsed once and 11 were unclear in the following 6 months.There was a difference between the 2 treatment intervals <12 months (12.5%, 2/16 cases) and ≥12 months (55.5%, 10/18 cases). After the third treatment, with an interval of 6 to 15 months, 1 of 15 patients(6.67%) relapsed and the rest were stable.In addition, there was a significant difference in the mean accumulated steroid dose of 20 patients between 6 months before treatment [(2.50±0.87) g ]and 6 months after treatment[(1.30±0.97) g;t=6.05, P=0.001]. Of the 15 patients after RTX treatment for 6-12 months Tacrolimus was reduced from [(1.62±0.77) mg/24 h ] to [(0.62±0.96) mg/24 h;t=6.80, P=0.000]. Two patients after RTX first infusion had chest tightness, palpitations, nausea, vomiting, dizziness, and headache, 3 cases had mild upper respiratory tract infection and 1 case had severe pulmonary infection. Conclusion Long-term follow-up of FRNS children treated with RTX turns out to be safe and effective.