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Poster Networking

Inherited Bleeding Disorders and Inhibitors

PB0506 - Influence of F8 gene mutation on outcome in immune tolerance induction of hemophilia A children with inhibitors

Monday, June 24, 2024
13:45 – 14:45 ICT
Room: Exhibition Hall

    Presenting Author(s)

  • Zekun Li, PhD

    Ph.D.
    Department II of Hematology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, China
    Beijing, Beijing, China (People's Republic)

    • Co-Author(s)

  • Zhenping Chen

    Associate professor
    Hematologic Diseases Laboratory, Hematology Center, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, ChinaChildren’s Health, Beijing, 100045, China
    Beijing, Beijing, China (People's Republic)

  • Jie Sun, MD

    Hemophilia Comprehensive Care Center, Beijing Children’s Hospital, Capital Medical University
    Hemophilia Comprehensive Care Center,Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health
    Beijing, Beijing, China (People's Republic)

  • Jialu Zhang

    Resident physician
    Department II of Hematology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, China
    Beijing, Beijing, China (People's Republic)

  • GL

    Gang Li

    researcher
    Beijing Children's Hospital
    Beijing, Beijing, China (People's Republic)

  • Zhengping Li, Medical Doctor in progress

    M.D. in progress
    zhengp_li@163.com
    Beijing, Beijing, China (People's Republic)

  • GL

    Guoqing Liu

    professor
    Beijing Children’s Hospital
    Beijing, Beijing, China (People's Republic)

  • Wanru Yao, MA

    Doctor
    Haemophilia 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, China, 100045
    Beijing, Beijing, China (People's Republic)

  • DA

    Di Ai

    PhD student
    Beijing Children’s Hospital
    Beijing, Beijing, China (People's Republic)

  • Runhui Wu, PhD, MD

    Professor
    Department of Hematology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, China
    Beijing, Beijing, China (People's Republic)

Background: FVIII consists of a heavy chain (A1-a1-A2-a2-B domain) and a light chain (a3-A3-C1-C2) .Type of F8 mutations constitutes an important predictor of ITI outcome. The role of F8 genotype and different domain are not well established.

Aims: To investigate the relationship between F8 genotype and outcome of ITI in hemophilia A children with inhibitors.

Methods: We sequentially included patients with F8 genotype detected from registry of Beijing Children’s hospital from January 2017 to December 2021. Patients were subjected to low-dose ITI regimen (FVIII 50IU/kg. QoD). All patients with higher titer inhibitors (≥40BU) or refractory to ITI were added rituximab (ITI-Ritux).

Results: Totally 164 patients with median age of 4.3 years at ITI start were included and followed more than 24 months. At the end of ITI, 87 (53.0%) only received ITI, 77 (47.0%) combined with rituximab. Success achieved in 141 (86%) patients. Those with intron 22 inversion, nonsense, and frameshift mutation showed similar success rate (90.9%, 90.6% and 88.2%, respectively). Twenty-four patients with large deletion or duplication showed the lowest success rate of 58.3%. Of these 24 patients, 14 patients had F8 gene only affected in heavy chain (not included B domain), all 5 patients succeed with “only” A1 domain (exon1-7) affected, 3 patients even without combining rituximab. Whereas, all 3 patients failure with “only” A2 domain (exon 8-13) affected. Another “all patients failure” occurred in the three patients with F8 deletion which span B domain. Except for these three patients, those with A2 domain affected achieved lower success rate than others 37.5% vs 84.6% (p=0.056).

Conclusion(s): Similar success rate was achieved in inhibitor patients with F8 gene of intron 22 inversion, nonsense or frameshift mutation. Failure likely to occur in those with F8 large deletion or duplication especially with A2 domain affected or deletion spanning B domain.