Low‐dose immune tolerance induction alone or with immunosuppressants according to prognostic risk factors in Chinese children with hemophilia A inhibitors
Abstract Background In developing countries, children with hemophilia A (HA) with high‐titer inhibitor and poor immune tolerance induction (ITI) prognostic risk(s) cannot afford the recommended high‐ or intermediate‐dose ITI. Objectives To determine the efficacy of low‐dose ITI (plasma‐derived facto...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-07-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/rth2.12562 |
| _version_ | 1797714343827079168 |
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| author | Zekun Li Zhenping Chen Guoqing Liu Xiaoling Cheng Wanru Yao Kun Huang Gang Li Yingzi Zhen Xinyi Wu Siyu Cai Man‐Chiu Poon Runhui Wu |
| author_facet | Zekun Li Zhenping Chen Guoqing Liu Xiaoling Cheng Wanru Yao Kun Huang Gang Li Yingzi Zhen Xinyi Wu Siyu Cai Man‐Chiu Poon Runhui Wu |
| author_sort | Zekun Li |
| collection | DOAJ |
| description | Abstract Background In developing countries, children with hemophilia A (HA) with high‐titer inhibitor and poor immune tolerance induction (ITI) prognostic risk(s) cannot afford the recommended high‐ or intermediate‐dose ITI. Objectives To determine the efficacy of low‐dose ITI (plasma‐derived factor VIII [FVIII]/von Willebrand factor at 50 FVIII IU/kg every other day) by itself (ITI‐alone) or combined with immunosuppressants rituximab and prednisone (ITI‐IS) in children with HA with high‐titer inhibitor. Methods All enrolled patients had pre‐ITI inhibitor ≥10 BU. We used ITI‐alone if inhibitor titer was <40 BU pre‐ITI and during ITI, and ITI‐IS if titer was ≥100 BU (historic) or ≥40 BU (pre‐ or during ITI) or if the patient was nonresponsive on ITI‐alone. Results Fifty‐six children were analyzable, with median historic peak inhibitor titer 48.0 BU and followed for median 31.4 months. Overall, 35 (62.5%) achieved phase 2 success with negative inhibitor and normal FVIII recovery. The phase 2 success rate was 95% for the 20 patients receiving ITI‐alone. For the 36 patients receiving ITI‐IS, the phase 2 success rate was 44.4%, but would increase to 63.6% if the 14 patients with historic peak inhibitor titer ≥100 BU (and having phase 2 success rate of only 14.3%) were excluded. One patient developed repeated infection after IS treatment. Relapse occurred in 11.4% (4/35) patients with phase 2 success associated with rapid ITI dose reduction or irregular post‐ITI FVIII prophylaxis. Our strategy reduced the cost from high‐dose ITI by 74% to 90%. Conclusion The use of low‐dose ITI with or without immunosuppressants according to ITI prognostic risk(s) is a clinically and economically feasible strategy for eradicating inhibitors in children with HA, particularly for those with historic peak inhibitor titer <100 BU. |
| first_indexed | 2024-03-12T07:50:30Z |
| format | Article |
| id | doaj.art-208b232bc9334bad914ad28245e8d49d |
| institution | Directory Open Access Journal |
| issn | 2475-0379 |
| language | English |
| last_indexed | 2024-03-12T07:50:30Z |
| publishDate | 2021-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj.art-208b232bc9334bad914ad28245e8d49d2023-09-02T20:38:20ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792021-07-0155n/an/a10.1002/rth2.12562Low‐dose immune tolerance induction alone or with immunosuppressants according to prognostic risk factors in Chinese children with hemophilia A inhibitorsZekun Li0Zhenping Chen1Guoqing Liu2Xiaoling Cheng3Wanru Yao4Kun Huang5Gang Li6Yingzi Zhen7Xinyi Wu8Siyu Cai9Man‐Chiu Poon10Runhui 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 National Center for Children’s Health Capital Medical University 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 National Center for Children’s Health Capital Medical University 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 National Center for Children’s Health Capital Medical University Beijing ChinaDepartment of Pharmacy, Beijing Children’s Hospital, National Center for Children’s Health Capital Medical University 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 National Center for Children’s Health Capital Medical University 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 National Center for Children’s Health Capital Medical University 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 National Center for Children’s Health Capital Medical University 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 National Center for Children’s Health Capital Medical University 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 National Center for Children’s Health Capital Medical University Beijing ChinaCenter for Clinical Epidemiology and Evidence‐based Medicine Capital Medical University Beijing ChinaDepartments of Medicine, Pediatrics and Oncology Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program Foothills Hospital Alberta Health Services University of Calgary Cumming School of Medicine Calgary AB CanadaHemophilia 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 National Center for Children’s Health Capital Medical University Beijing ChinaAbstract Background In developing countries, children with hemophilia A (HA) with high‐titer inhibitor and poor immune tolerance induction (ITI) prognostic risk(s) cannot afford the recommended high‐ or intermediate‐dose ITI. Objectives To determine the efficacy of low‐dose ITI (plasma‐derived factor VIII [FVIII]/von Willebrand factor at 50 FVIII IU/kg every other day) by itself (ITI‐alone) or combined with immunosuppressants rituximab and prednisone (ITI‐IS) in children with HA with high‐titer inhibitor. Methods All enrolled patients had pre‐ITI inhibitor ≥10 BU. We used ITI‐alone if inhibitor titer was <40 BU pre‐ITI and during ITI, and ITI‐IS if titer was ≥100 BU (historic) or ≥40 BU (pre‐ or during ITI) or if the patient was nonresponsive on ITI‐alone. Results Fifty‐six children were analyzable, with median historic peak inhibitor titer 48.0 BU and followed for median 31.4 months. Overall, 35 (62.5%) achieved phase 2 success with negative inhibitor and normal FVIII recovery. The phase 2 success rate was 95% for the 20 patients receiving ITI‐alone. For the 36 patients receiving ITI‐IS, the phase 2 success rate was 44.4%, but would increase to 63.6% if the 14 patients with historic peak inhibitor titer ≥100 BU (and having phase 2 success rate of only 14.3%) were excluded. One patient developed repeated infection after IS treatment. Relapse occurred in 11.4% (4/35) patients with phase 2 success associated with rapid ITI dose reduction or irregular post‐ITI FVIII prophylaxis. Our strategy reduced the cost from high‐dose ITI by 74% to 90%. Conclusion The use of low‐dose ITI with or without immunosuppressants according to ITI prognostic risk(s) is a clinically and economically feasible strategy for eradicating inhibitors in children with HA, particularly for those with historic peak inhibitor titer <100 BU.https://doi.org/10.1002/rth2.12562hemophilia Ahigh‐titer inhibitorimmune tolerance inductionlow‐doserituximab |
| spellingShingle | Zekun Li Zhenping Chen Guoqing Liu Xiaoling Cheng Wanru Yao Kun Huang Gang Li Yingzi Zhen Xinyi Wu Siyu Cai Man‐Chiu Poon Runhui Wu Low‐dose immune tolerance induction alone or with immunosuppressants according to prognostic risk factors in Chinese children with hemophilia A inhibitors Research and Practice in Thrombosis and Haemostasis hemophilia A high‐titer inhibitor immune tolerance induction low‐dose rituximab |
| title | Low‐dose immune tolerance induction alone or with immunosuppressants according to prognostic risk factors in Chinese children with hemophilia A inhibitors |
| title_full | Low‐dose immune tolerance induction alone or with immunosuppressants according to prognostic risk factors in Chinese children with hemophilia A inhibitors |
| title_fullStr | Low‐dose immune tolerance induction alone or with immunosuppressants according to prognostic risk factors in Chinese children with hemophilia A inhibitors |
| title_full_unstemmed | Low‐dose immune tolerance induction alone or with immunosuppressants according to prognostic risk factors in Chinese children with hemophilia A inhibitors |
| title_short | Low‐dose immune tolerance induction alone or with immunosuppressants according to prognostic risk factors in Chinese children with hemophilia A inhibitors |
| title_sort | low dose immune tolerance induction alone or with immunosuppressants according to prognostic risk factors in chinese children with hemophilia a inhibitors |
| topic | hemophilia A high‐titer inhibitor immune tolerance induction low‐dose rituximab |
| url | https://doi.org/10.1002/rth2.12562 |
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