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, 100045, 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, China 100045.
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, China 100045.
Thromb Res. 2023 Jun;226:56-60. doi: 10.1016/j.thromres.2023.04.002. Epub 2023 Apr 11.
The predictors of immune tolerance induction (ITI) outcomes in hemophilia A (HA) patients with the same F8 genetic background have not yet been evaluated, although the F8 genotype is strongly associated with ITI response. This study aims to explore the predictors of ITI outcomes in the same F8 genetic background by focusing on intron 22 inversion (Inv22) patients with high-responding inhibitors.
HA children with Inv22 and high-responding inhibitors who received low-dose ITI therapy over 24 months were included in this study. ITI outcomes were centrally assessed at the 24th month of treatment. The predictive ability of clinical variables to identify ITI success was determined using the receiver operating characteristic (ROC) curve, and the predictor of ITI outcomes was analyzed on the multivariable Cox model.
Among the 32 patients investigated, 23 (71.9 %) achieved success. In univariate analysis, interval time from inhibitor diagnosis to ITI start (interval-time) was significantly associated with ITI success (P = 0.001); however, inhibitor titers showed no significance (P > 0.05). The interval-time demonstrated a good predictive value for ITI success with the area under the ROC curve of 0.855 (P = 0.002), and the cutoff value was 25.8 months (sensitivity, 87.0 %; specificity, 88.9 %). In the multivariable Cox model which considered success rate and time to success, interval-time was the only independent predictor (<25.8 months vs. ≥25.8 months, P = 0.002).
The interval-time was first identified as a unique predictor of ITI outcomes in HA patients with high-responding inhibitors under the same F8 genetic background (Inv22). An interval-time of <25.8 months was associated with increased ITI success and reduced time to success.
在具有相同 F8 遗传背景的血友病 A (HA) 患者中，免疫耐受诱导 (ITI) 结果的预测因素尚未得到评估，尽管 F8 基因型与 ITI 反应密切相关。本研究旨在通过关注具有高反应性抑制剂的内含子 22 倒位 (Inv22) 患者，探讨相同 F8 遗传背景下 ITI 结果的预测因素。
本研究纳入了接受为期 24 个月的低剂量 ITI 治疗的 Inv22 且具有高反应性抑制剂的 HA 儿童患者。在治疗的第 24 个月对 ITI 结果进行中心评估。使用受试者工作特征 (ROC) 曲线确定临床变量预测 ITI 成功的能力，并在多变量 Cox 模型中分析 ITI 结果的预测因素。
在所研究的 32 名患者中，23 名 (71.9%) 获得成功。在单因素分析中，从抑制剂诊断到 ITI 开始的时间间隔 (interval-time) 与 ITI 成功显著相关 (P=0.001)；然而，抑制剂滴度无显著意义 (P>0.05)。Interval-time 对 ITI 成功具有良好的预测价值，ROC 曲线下面积为 0.855 (P=0.002)，截断值为 25.8 个月 (敏感性，87.0%；特异性，88.9%)。在考虑成功率和成功时间的多变量 Cox 模型中，interval-time 是唯一的独立预测因素 (<25.8 个月与≥25.8 个月，P=0.002)。
首次发现，在具有相同 F8 遗传背景 (Inv22) 的高反应性抑制剂的 HA 患者中，interval-time 是 ITI 结果的独特预测因素。interval-time<25.8 个月与 ITI 成功率增加和成功时间缩短相关。
