两种小剂量利妥昔单抗二线治疗儿童原发性免疫性血小板减少症的效果及安全性比较

Comparison of the efficacy and safety of 2 low-dose rituximab regimens in the second-line treatment of primary immune thrombocytopenia in children

目的比较两种小剂量利妥昔单抗治疗方案治疗儿童原发性免疫性血小板减少症(ITP)的效果及安全性。方法前瞻性队列研究。将2018年1月至2021年3月北京儿童医院血液肿瘤中心收治共90例ITP患儿纳入研究。单剂组利妥昔单抗用量为375 mg/m^(2)(最大剂量600 mg),只用1次;四剂组利妥昔单抗用量为100 mg/(次·周)[体重≥30 kg者200 mg/(次·周)],连续4周,每周1次。采用秩和检验、χ^(2)检验和Fisher确切概率法比较分析组间疗效、安全性及治疗费用等指标的差异。结果90例患儿中男41例、女49例,用药年龄6.8(4.1,10.0)岁,其中单剂组27例,四剂组63例,两组患儿在总有效率、完全有效率和部分有效率方面差异均无统计学意义[41%(11/27)比33%(21/63)、26%(7/27)比19%(12/63)、15%(4/27)比14%(9/63),χ^(2)=0.45、0.54、0.00,均P>0.05]。单剂组起效时间显著快于四剂组[1(1,1)比3(2,6)周,Z=-3.24,P=0.001]。单剂组比四剂组在持续有效率、1年时总有效率、1年时完全有效率、1年时部分有效率方面差异无统计学意义[33%(9/27)比30%(19/63)、30%(8/27)比24%(15/63)、19%(5/27)比14%(9/63)、11%(3/27)比10%(6/63),χ^(2)=0.09、0.34、0.04、0.00,均P>0.05]。两组在疗效持续时间、半年内复发率、1年内复发率、复发时间、不良反应率方面差异均无统计学意义(均P>0.05)。单剂组住院次数、住院天数和用药量显著低于四剂组[1(1,1)比4(4,4)次、5(4,7)比8(5,8)d、400(250,500)比400(400,800)mg,Z=-8.67、-3.03、-4.05,均P<0.05]。结论两种小剂量利妥昔单抗方案治疗儿童ITP的效果及安全性没有差异,但单剂小剂量利妥昔单抗方案更为经济和方便,更适合用于儿童ITP的二线治疗。

Objective To compare the efficacy and safety of 2 low-dose rituximab regimens in the treatment of children with primary immune thrombocytopenia(ITP).Methods A total of 90 ITP children admitted to the Hematology Oncology Center of Beijing Children′s Hospital from January 2018 to March 2021 were enrolled in this prospective cohort study.In the single-dose group,rituximab was given with a single dose of 375 mg/m^(2)(maximum dose 600 mg).In the 4-dose group,rituximab was given with a dose of 100 mg weekly(if body weight of the patient≥30 kg,increase dosage to 200 mg weekly)for 4 weeks.Wilcoxon Mann-Whitney test,Chi-square test and Fisher′s exact test were used to analyze the difference in efficacy,safety and treatment burden between two groups.Results Among the 90 children,41 were male and 49 were female,and the age of medication was 6.8(4.1,10.0)years.There were 27 cases in the single-dose group and 63 cases in the 4-dose group.There were no significant differences in overall response rate,complete response rate and partial response rate between the single-dose group and 4-dose group(41%(11/27)vs.33%(21/63),26%(7/27)vs.19%(12/63),15%(4/27)vs.14%(9/63),χ^(2)=0.45,0.54,0.00,all P>0.05).The single-dose group was earlier to get overall response than the 4-dose group(1(1,1)vs.3(2,6)weeks,Z=-3.24,P=0.001).There were no significant differences in the sustained response rate,the overall response rate in 1 year,the complete response rate in 1 year,and the partial response rate in 1 year between the single-dose group and the 4-dose group(33%(9/27)vs.30%(19/63),30%(8/27)vs.24%(15/63),19%(5/27)vs.14%(9/63),11%(3/27)vs.10%(6/63),χ^(2)=0.09,0.34,0.04,0.00,all P>0.05).There were no significant differences in the duration of overall response,recurrence rate within half a year and one year,recurrence time and rate of adverse events between the single-dose group and 4-dose group(all P>0.05).The number of hospitalizations,the duration of hospital stays and the dosage of the single-dose group were significantly lower than those of the 4-dose group(1(1,1)vs.4(4,4)times,5(4,7)vs.8(5,8)d,400(250,500)vs.400(400,800)mg,Z=-8.67,-3.03,-4.05,all P<0.05).Conclusions The single-dose rituximab regimen is comparable to 4-dose rituximab regimen in effectiveness and safety for treatment of children ITP,but more economical and convenient.The single-dose rituximab regimen is more suitable for the second-line treatment of children ITP.