Low-dose immune tolerance induction for severe hemophilia A inhibitor patients:Immunosuppressants are generally not necessary for inhibitor-titer below 200 BU/mL  

作　　者：Zhengping Li Jie Sun Zekun Li Zhenping Chen Guoqing Liu Wanru Yao Xiaoling Cheng Gang Li Yingzi Zhen Di Ai Yaohan Zhou Qianqian Mao Man-Chiu Poon Runhui Wu 

机构地区：[1]Hemophilia Comprehensive Care Center,Hematology Department,Hematology Center,Beijing Key Laboratory of Pediatric Hematology-Oncology,Key Laboratory of Major Diseases in Children,National Key Discipline of Pediatrics(Capital Medical University),Ministry of Education,Beijing Children’s Hospital,Capital Medical University,National Center for Children’s Health,Beijing,China [2]Hematologic Disease Laboratory,Hematology Department,Hematology Center,Beijing Key Laboratory of Pediatric Hematology-Oncology,Key Laboratory of Major Diseases in Children,National Key Discipline of Pediatrics(Capital Medical University),Ministry of Education,Beijing Pediatric Research Institute,Beijing Children’s Hospital,Capital Medical University,National Center for Children’s Health,Beijing,China [3]Department of Pharmacy,Beijing Children’s Hospital,Capital Medical University,National Center for Children’s Health,Beijing,China [4]Departments of Medicine,Pediatrics and Oncology,University of Calgary Cumming School of Medicine,Calgary,Canada

出　　处：《Pediatric Investigation》2024年第2期91-100,共10页儿科学研究（英文）

基　　金：Capital Health Development Research Project,Grant/Award Number:2022-2-2093;Beijing Research Ward Construction Demonstration Unit Project,Grant/Award Number:BCRW202101;National Natural Science Foundation of China,Grant/Award Number:82270133;Beijing Municipal Scienceand Technology Commission,Grant/Award Number:Z221100007422067。

摘　　要：Importance:It remained unclear that the efficacy comparison between low-dose immune tolerance induction(LD-ITI)incorporating immunosuppressants(IS)when severe hemophilia A(SHA)patients had inhibitor-titer≥200 Bethesda Units(BU)/mL(LD-ITI-IS^(200) regimen)and LD-ITI combining with IS when SHA patients had inhibitor-titer≥40 BU/mL(LD-ITI-IS^(40) regimen).Objective:To compare the efficacy of the LD-ITI-IS^(200) regimen with that of the LD-ITI-IS^(40) regimen for SHA patients with high-titer inhibitors.Methods:A prospective cohort study on patients receiving LD-ITI-IS^(200) compared to those receiving LD-ITI-IS^(40) from January 2021 to December 2023.Both received LD-ITI[FVIII 50 IU/kg every other day].IS(rituximab+prednisone)was added when peak inhibitor tier≥200 BU/mL in the LD-ITI-IS^(200) regimen and≥40 BU/mL in the LD-ITI-IS^(40) regimen.Success is defined as a negative inhibitor plus FVIII recovery≥66%of the expected.Results:We enrolled 30 patients on LD-ITI-IS^(200) and 64 patients on LD-ITI-IS^(40),with similar baseline clinical characteristics.A lower IS-use rate was discovered in the LD-ITI-IS^(200) regimen compared to the LD-ITI-IS^(40) regimen(30.0%vs.62.5%).The two regimens(LD-ITI-IS^(200) vs.LD-ITI-IS^(40))had similar success rate(70.0%vs.79.7%),median time to success(9.4 vs.10.6 months),and annualized bleeding rate during ITI(3.7 vs.2.8).The cost to success was lower for LD-ITI-IS^(200) than for LD-ITI-IS^(40)(2107 vs.3256 US Dollar/kg).Among patients with peak inhibitor-titer 40-199 BU/mL,10 non-IS-using(on LD-ITI-IS^(200) regimen)and 28 IS-using(on LD-ITI-IS^(40) regimen)had similar success rates(70.0%vs.78.6%)and time to success(9.0 vs.8.8 months).Interpretation:In LD-ITI,IS are not necessary for inhibitor titer<200 BU/mL.

关 键 词：Hemophilia A High-titer inhibitor Immune tolerance induction IMMUNOSUPPRESSANT LOW-DOSE 

分 类 号：R554.1[医药卫生—血液循环系统疾病]