Background Immune tolerance induction (ITI) therapy is currently unaffordable in China. Management of hemophilia A children with high-titer inhibitor is therefore a challenge. Aim To describe the ITI strategy using plasma-derived factor VIII/von Willebrand factor concentrate (pdFVIII/VWF) +/- immunosuppression and to report its efficacy in children with hemophilia A having poor-risk status for ITI success. Methods A prospective pilot study on children with hemophilia A having poor-risk status (all with at least inhibitor titer > 10 BU pre-ITI initiation). Patients received similar to 50 IU/kg FVIII every other day using domestic intermediate purity pdFVIII/VWF products, either alone or in combination with rituximab +/- prednisone. Results Sixteen patients with median age 2.9 (range, 2.2-13.2) years and median pre-ITI inhibitor titer 30.7 (range, 10.4-128) BU were enrolled. Analysis at median 14.7 (range, 12.4-22.6) months' follow-up showed a total response rate of 87.5%. This included success (achieving inhibitor BU) in 13 patients (81.3%) in a median of 8.8 (range, 3.2-11.8) months, and partial success (achieving inhibitor BU but > 0.6BU) in 1 (6.3%). Compared to the pre-ITI period, the mean bleeds/month during ITI was 0.51 (64.0% reduction), and joint bleeds/month was 0.34 (64.3% reduction). This low-dose ITI strategy cost less by 70% to 87% than that for the high-dose FVIII regimen. No severe adverse events were observed. Conclusion This low-dose ITI strategy of pdFVIII/VWF +/- immunosuppression achieved relatively satisfactory outcomes in children with hemophilia A inhibitor having poor-risk status. This low-dose regimen showed economic advantages and is therefore suitable for using in China. However, further study in a larger cohort with a longer follow-up time is needed.
基金：
Capital Health Development Research Project [2018-2-2094]; Beijing Municipal Science and Technology CommissionBeijing Municipal Science & Technology Commission [Z181100001718182]; National Science and Technology major projects [2017ZX09304029004]; Beijing Natural Science Foundation of ChinaBeijing Natural Science Foundation [7162059]; Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding [ZY201404]
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
无
最新[2023]版：
大类|3 区医学
小类|3 区血液学3 区外周血管病
第一作者：
第一作者机构：[1]Capital Med Univ, Hemophilia Work Grp, Hematol Oncol Ctr, Beijing Childrens Hosp, Beijing, Peoples R China;
通讯作者：
通讯机构：[1]Capital Med Univ, Hemophilia Work Grp, Hematol Oncol Ctr, Beijing Childrens Hosp, Beijing, Peoples R China;[7]Capital Med Univ, Hemophilia Work Grp, Beijing Childrens Hosp, 56 Nanlishi Rd, Beijing 100045, Peoples R China
推荐引用方式(GB/T 7714)：
Li Zekun,Chen Zhenping,Cheng Xiaoling,et al.Low-dose immune tolerance induction for children with hemophilia A with poor-risk high-titer inhibitors: A pilot study in China[J].Research and practice in thrombosis and haemostasis.2019,3(4):741-748.doi:10.1002/rth2.12248.
APA：
Li, Zekun,Chen, Zhenping,Cheng, Xiaoling,Wu, Xinyi,Li, Gang...&Wu, Runhui.(2019).Low-dose immune tolerance induction for children with hemophilia A with poor-risk high-titer inhibitors: A pilot study in China.Research and practice in thrombosis and haemostasis,3,(4)
MLA：
Li, Zekun,et al."Low-dose immune tolerance induction for children with hemophilia A with poor-risk high-titer inhibitors: A pilot study in China".Research and practice in thrombosis and haemostasis 3..4(2019):741-748
