Low‐dose immune tolerance induction in children with severe hemophilia A with high‐titer inhibitors: Type of factor 8 mutation and outcomes
Abstract Background No studies evaluated the role of F8 mutations in outcomes for low‐dose immune tolerance induction (ITI) in people with severe hemophilia A (SHA) with high‐titer inhibitors. Objectives To explore the association between F8 mutation types and low‐dose ITI outcomes in children with...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/rth2.12824 |
| _version_ | 1797757637885952000 |
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| author | Jie Sun Zekun Li Gang Li Kun Huang Di Ai Guoqing Liu Wanru Yao Xingjuan Xie Hao Gu Yingzi Zhen Zhenping Chen Runhui Wu |
| author_facet | Jie Sun Zekun Li Gang Li Kun Huang Di Ai Guoqing Liu Wanru Yao Xingjuan Xie Hao Gu Yingzi Zhen Zhenping Chen Runhui Wu |
| author_sort | Jie Sun |
| collection | DOAJ |
| description | Abstract Background No studies evaluated the role of F8 mutations in outcomes for low‐dose immune tolerance induction (ITI) in people with severe hemophilia A (SHA) with high‐titer inhibitors. Objectives To explore the association between F8 mutation types and low‐dose ITI outcomes in children with SHA with high‐titer inhibitors. Methods 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, F8 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. Results Of 104 children included, 101 had F8 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%; p = 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%; p = 0.001) and a shorter time to success (mean time, 9.3 months vs. 13.2 months; p = 0.04) compared to those in the high‐risk group. In multivariable logistic regression, F8 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. Conclusions Types of F8 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. |
| first_indexed | 2024-03-12T18:18:32Z |
| format | Article |
| id | doaj.art-c76cb85c86174975a8659eaaeae1c4fe |
| institution | Directory Open Access Journal |
| issn | 2475-0379 |
| language | English |
| last_indexed | 2024-03-12T18:18:32Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj.art-c76cb85c86174975a8659eaaeae1c4fe2023-08-02T09:02:45ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792022-10-0167n/an/a10.1002/rth2.12824Low‐dose immune tolerance induction in children with severe hemophilia A with high‐titer inhibitors: Type of factor 8 mutation and outcomesJie Sun0Zekun Li1Gang Li2Kun Huang3Di Ai4Guoqing Liu5Wanru Yao6Xingjuan Xie7Hao Gu8Yingzi Zhen9Zhenping Chen10Runhui Wu11Hemophilia 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 ChinaHemophilia 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 ChinaHematologic 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 ChinaHemophilia 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 ChinaHemophilia 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 ChinaHemophilia 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 ChinaHemophilia 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 ChinaHemophilia 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 ChinaHemophilia 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 ChinaHemophilia 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 ChinaHematologic 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 ChinaHemophilia 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 ChinaAbstract Background No studies evaluated the role of F8 mutations in outcomes for low‐dose immune tolerance induction (ITI) in people with severe hemophilia A (SHA) with high‐titer inhibitors. Objectives To explore the association between F8 mutation types and low‐dose ITI outcomes in children with SHA with high‐titer inhibitors. Methods 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, F8 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. Results Of 104 children included, 101 had F8 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%; p = 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%; p = 0.001) and a shorter time to success (mean time, 9.3 months vs. 13.2 months; p = 0.04) compared to those in the high‐risk group. In multivariable logistic regression, F8 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. Conclusions Types of F8 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.https://doi.org/10.1002/rth2.12824F8 mutationhigh‐titer inhibitorimmune tolerance inductionlow‐dosepredictorsevere hemophilia A |
| spellingShingle | Jie Sun Zekun Li Gang Li Kun Huang Di Ai Guoqing Liu Wanru Yao Xingjuan Xie Hao Gu Yingzi Zhen Zhenping Chen Runhui Wu Low‐dose immune tolerance induction in children with severe hemophilia A with high‐titer inhibitors: Type of factor 8 mutation and outcomes Research and Practice in Thrombosis and Haemostasis F8 mutation high‐titer inhibitor immune tolerance induction low‐dose predictor severe hemophilia A |
| title | Low‐dose immune tolerance induction in children with severe hemophilia A with high‐titer inhibitors: Type of factor 8 mutation and outcomes |
| title_full | Low‐dose immune tolerance induction in children with severe hemophilia A with high‐titer inhibitors: Type of factor 8 mutation and outcomes |
| title_fullStr | Low‐dose immune tolerance induction in children with severe hemophilia A with high‐titer inhibitors: Type of factor 8 mutation and outcomes |
| title_full_unstemmed | Low‐dose immune tolerance induction in children with severe hemophilia A with high‐titer inhibitors: Type of factor 8 mutation and outcomes |
| title_short | Low‐dose immune tolerance induction in children with severe hemophilia A with high‐titer inhibitors: Type of factor 8 mutation and outcomes |
| title_sort | low dose immune tolerance induction in children with severe hemophilia a with high titer inhibitors type of factor 8 mutation and outcomes |
| topic | F8 mutation high‐titer inhibitor immune tolerance induction low‐dose predictor severe hemophilia A |
| url | https://doi.org/10.1002/rth2.12824 |
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