Sun Jie, Li Zekun, Li Gang, Huang Kun, Ai Di, Liu Guoqing, Yao Wanru, Xie Xingjuan, Gu Hao, Zhen Yingzi, Chen Zhenping, Wu Runhui
Hemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital Capital Medical University, National Center for Children's Health Beijing China.
Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital Capital Medical University, National Center for Children's Health Beijing China.
Res Pract Thromb Haemost. 2022 Oct 26;6(7):e12824. doi: 10.1002/rth2.12824. eCollection 2022 Oct.
No studies evaluated the role of mutations in outcomes for low-dose immune tolerance induction (ITI) in people with severe hemophilia A (SHA) with high-titer inhibitors.
To explore the association between mutation types and low-dose ITI outcomes in children with SHA with high-titer inhibitors.
Children SHA with high-titer inhibitors who received low-dose ITI therapy at least for 1 year were included in this study. Based on the risk of inhibitor development, mutations were classified into a high-risk group and a non-high-risk group. Rapid tolerance and the final ITI outcomes were assessed at the 12th and 24th month of treatment, respectively, and the predictor of outcomes was analyzed.
Of 104 children included, 101 had mutations identified. The children with non-high-risk mutations presented a higher rate of rapid tolerance than those with high-risk mutations (61.0% vs. 29.2%; = 0.006). Among 72 children beyond 24 months of ITI, 55 children (76.4%) achieved success, 3 (4.2%) achieved partial success, and 14 (19.4%) failed. The children in the non-high-risk group showed a higher success rate (86.8% vs. 43.8%; = 0.001) and a shorter time to success (mean time, 9.3 months vs. 13.2 months; = 0.04) compared to those in the high-risk group. In multivariable logistic regression, mutations were an independent predictor of ITI success (non-high-risk group vs. high-risk group, adjusted odds ratio [OR], 20.3; 95% confidence interval [CI], 3.5-117.8), as was the interval from inhibitor diagnosis to ITI start (adjusted OR, 0.95; 95% CI, 0.90-0.99). They remained the significant predictors when success time was taken into account in a Cox model.
Types of mutation were a key predictor of outcomes for low-dose ITI in children with SHA with high-titer inhibitors. It can help to stratify the prognosis and guide clinical decisions.
尚无研究评估突变在高滴度抑制物的重度甲型血友病（SHA）患者低剂量免疫耐受诱导（ITI）结局中的作用。
探讨高滴度抑制物的SHA儿童患者的突变类型与低剂量ITI结局之间的关联。
本研究纳入了接受低剂量ITI治疗至少1年的高滴度抑制物的SHA儿童患者。根据抑制物产生的风险，将突变分为高风险组和非高风险组。分别在治疗的第12个月和第24个月评估快速耐受情况和最终ITI结局，并分析结局的预测因素。
在纳入的104例儿童患者中，101例检测到有突变。非高风险突变的儿童患者快速耐受率高于高风险突变的儿童患者（61.0%对29.2%；P = 0.006）。在接受ITI治疗超过24个月的72例儿童患者中，55例（76.4%）获得成功，3例（4.2%）获得部分成功，14例（19.4%）失败。与高风险组相比，非高风险组儿童患者的成功率更高（86.8%对43.8%；P = 0.001），且成功所需时间更短（平均时间为9.3个月对13.2个月；P = 0.04）。在多变量逻辑回归分析中，突变是ITI成功的独立预测因素（非高风险组对高风险组，调整后的比值比[OR]为20.3；95%置信区间[CI]为3.5 - 117.8），从抑制物诊断到开始ITI的时间间隔也是如此（调整后的OR为0.95；95%CI为0.90 - 0.99）。在Cox模型中考虑成功时间时，它们仍然是显著的预测因素。
突变类型是高滴度抑制物的SHA儿童患者低剂量ITI结局的关键预测因素。它有助于对预后进行分层并指导临床决策。
