Li Zhengping, Sun Jie, Li Zekun, Chen Zhenping, Liu Guoqing, Yao Wanru, Li Gang, Zhen Yingzi, Cheng Xiaoling, Ai Di, Huang Kun, Poon Man-Chiu, 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, 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, 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, 100045, China.
Thromb Res. 2023 May;225:33-38. doi: 10.1016/j.thromres.2023.02.016. Epub 2023 Mar 5.
Shorter interval-time from inhibitor detection to starting immune tolerance induction (ITI) might predict better ITI outcomes for severe Hemophilia A (SHA) patients with high-risk-inhibitors. However, the prediction-impact of interval-time for these patients on low-dose ITI strategy remained unclear.
To explore the relationship between interval-time and low-dose ITI outcomes in Chinese SHA children with high-risk-inhibitors.
This was a single-center, retrospective study on SHA children with high-risk-inhibitors (each with immediate pre-ITI inhibitor titer>10 Bethesda Units/mL) undergoing low-dose ITI strategy for ≥24 months. ITI outcomes and their predictive factors were evaluated at the 24th month treatment for each patient. The predictive ability of interval-time on ITI success was determined using receiver operating characteristic (ROC) curve.
Among 47 patients investigated, 34 (72.3 %) achieved success. Independent predictor for ITI-outcome on multivariate analysis included the interval-time (p = 0.007) and peak inhibitor-titer (p = 0.011). Shorter interval-time predicted ITI success [cut-off value = 22.3 months, area under ROC-curve (AUC) = 0.701] and early-ITI success within 12 month (cut-off value = 9.4 months AUC = 0.704). Linear regression analysis suggested each month interval-time delay delayed success by 0.1552 month. Unlike the interval-time, peak inhibitor-titer had no success-predictive value in high-peak inhibitor-titer patients on ITI with immunosuppressants.
Interval-time represented a strong predictive value for outcomes in our low-dose ITI strategy for SHA patients with high-risk-inhibitors. Shorter interval-time was associated with higher success rate and earlier success achievement. The respective interval-time cut-off values were 22.3 months for ITI success and 9.4 months for early-success.
对于患有高风险抑制物的重度甲型血友病（SHA）患者，从检测到抑制物到开始免疫耐受诱导（ITI）的间隔时间较短可能预示着更好的ITI结果。然而，这些患者的间隔时间对低剂量ITI策略的预测影响仍不清楚。
探讨中国患有高风险抑制物的SHA儿童的间隔时间与低剂量ITI结果之间的关系。
这是一项针对接受低剂量ITI策略≥24个月的患有高风险抑制物的SHA儿童（每位患者ITI前即刻抑制物滴度>10 Bethesda单位/mL）的单中心回顾性研究。在每位患者治疗的第24个月评估ITI结果及其预测因素。使用受试者工作特征（ROC）曲线确定间隔时间对ITI成功的预测能力。
在47例接受调查的患者中，34例（72.3%）获得成功。多变量分析中ITI结果的独立预测因素包括间隔时间（p = 0.007）和抑制物峰值滴度（p = 0.011）。较短的间隔时间预示着ITI成功[临界值 = 22.3个月，ROC曲线下面积（AUC） = 0.701]以及12个月内的早期ITI成功（临界值 = 9.4个月，AUC = 0.704）。线性回归分析表明，间隔时间每延迟1个月，成功时间就延迟0.1552个月。与间隔时间不同，在接受免疫抑制剂ITI治疗的高抑制物峰值滴度患者中，抑制物峰值滴度没有成功预测价值。
在我们针对患有高风险抑制物的SHA患者的低剂量ITI策略中，间隔时间对结果具有很强的预测价值。较短的间隔时间与更高的成功率和更早的成功实现相关。ITI成功的间隔时间临界值为22.3个月，早期成功的临界值为9.4个月。
