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90例临床观察

Clinical observation on 90 children with primary immune thrombocytopenia treated with low-dose rituximab as second-line therapy

目的探讨小剂量利妥昔单抗二线治疗儿童免疫性血小板减少症(ITP)的有效性、安全性及疗效预判因素,为开展临床治疗提供依据。方法单中心、前瞻性地收集2018年1月—2021年3月应用小剂量利妥昔单抗单剂或四剂二线治疗的90例ITP患儿的临床资料,分析疗效、安全性及预后影响因素。结果90例患儿中,中位用药年龄6.9(1.1~15.9)岁,中位病程9(2~98)个月;其中63例使用四剂方案,27例使用单剂方案,两种方案患者基线齐同。总有效(OR)率为35.6%,完全有效(CR)率为21.1%,部分有效(PR)率为14.4%;中位起效时间为2(1~12)周;持续有效(SR)率为31.1%,中位持续时间为49(15~51)周。用药1年后OR率为25.6%:CR率为15.6%,PR率为10%。半年后复发率为12.5%,1年时复发率为28.1%,中位复发时间为35(16~52)周。无长期不良反应发生及感染风险增加。比较OR、无效(NR)两组病例,仅抗甲状腺抗体阳性患者NR率较高(P=0.027);比较SR、非SR两组病例,仅抗甲状腺抗体阳性患者SR率较低(P=0.002)。结论小剂量利妥昔单抗二线治疗儿童ITP有效、安全,适用于儿童ITP的二线治疗;抗甲状腺抗体阳性可能预示小剂量利妥昔单抗疗效不佳,具体机制有待进一步探索。

Objective To investigate the efficacy,safety and prognostic factors of low-dose rituximab in the second-line treatment of children with immune thrombocytopenia(ITP).Methods The clinical data of 90 children with ITP treated with single-dose or four-dose low-dose rituximab as second-line therapy from January 2018 to March 2021 were collected prospectively in a single center.We analyzed the efficacy,safety and prognostic factors through the clinical data.Results We Total 90 children were enrolled.The median age of treatment was 6.9(1.1~15.9)years,and the median course of disease was 9(2~98)months;Among them,63 cases used the four-dose regimen and 27 cases used the single-dose regimen.The baseline of patients between the two regimens was the same.35.6%achieved overall response(OR),including 21.1%got complete response(CR)and 14.4%got partial response(PR);The median onset time was 2(1~12)weeks.The sustained response(SR)ratewas 31.1%,and the median duration was 49(15~51)weeks.One year after treatment,the OR rate was 25.6%,of which the CR rate was 15.6%and the PR rate was 10%.The recurrence rate was 12.5%after half a year,28.1%at one year,and the median recurrence time was 35(16~52)weeks.There was no long-term adverse reaction and increased risk of infection.Comparing the clinical data of OR group and non-response(NR)group,only antithyroid antibody positive patients had higher NR rate(P=0.027);Comparing the SR group and the non-SR group,only antithyroid antibody positive patients had lower SR rate(P=0.002).Conclusions Low-dose rituximab is effective and safe in the second-line treatment of ITP in children,which is suitable for the second-line treatment of ITP in children;The positive antithyroid antibody may indicate the poor efficacy of low-dose rituximab,and the specific mechanism needs further exploring.