VPB1166 - Eradication of FIX inhibitor in haemophilia B children: A retrospective study from haemophilia pediatric comprehensive care center of China

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

Zekun Li, PhD

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

Co-Author(s)

GL

Guoqing LIU

Attending physician
Beijing Children’s Hospital, Capital Medical University
Bejing, Beijing, China (People's Republic)
WY

Wanru YAO

Attending physician
Beijing Children’s Hospital, Capital Medical University
Beijing, Beijing, China (People's Republic)
ZC

Zhenping CHEN

Professor
Beijing Children’s Hospital, Capital Medical University
Beijing, Beijing, China (People's Republic)
MP

Man-Chiu Poon

Clinical Professor; Professor Emeritus of Medicine - Paediatrics and Oncology
Division of Hematology and Hematological Malignancies, Department of Medicine, University of Calgary, Calgary, AB, Canada
Calgary, Alberta, Canada
RW

Runhui Wu

Director and Physician in Chief
Beijing Children’s Hospital, Capital Medical University, Beijing, China
Beijing, Beijing, China (People's Republic)

Background: Development of hemophilia B inhibitors (HBI) results in ineffectiveness of FIX replacement therapy. Inhibitor eradication by immune tolerance induction (ITI) is therefore necessary. In HBI, ITI even at high FIX dose is less effective and has a higher risk of severe complications.

Aims: To characterize the clinical features and outcome of ITI in HBI.

Methods: This is a single Chinese pediatric hemophilia center retrospective study. We used low-dose ITI (25-50 FIX IU/kg/three-times-weekly to every-other-day) with domestic prothrombin complex concentrate, combined with two successive immunosuppressive (IS) regimens.

Results: Sixteen HBI children, representing 5.7% of all and 14.4% of our severe registered HB patients, were enrolled. Seven cases reported allergic reactions proximal to inhibitor development. The historic peak inhibitor titer was median 54.2 (range 4.7-512) BU, and 15 (93.8%) had high-titer inhibitors. Twelve patients adherent to ITI were analyzable. Of the nine ITI patients who received rituximab/prednisone (IS Regimen-1), 4 achieved tolerization in 1.4-43.3 months. Two subsequently relapsed but re-tolerized after a second course of IS Regimen-1. During ITI, the median treated bleed was 0.39/month (82.7% bleed reduction from before ITI), and the incidence of allergic reaction and nephrotic syndrome complications was each at 22% (2/9). Three ITI patients received modified “Beutel” protocol (IS Regimen-2) using multiple-IS-drugs, and two had rapid tolerization (0.8 and 1.8 months).

Conclusion(s): Inhibitor eradication could be achieved by this low-dose ITI protocol using PCC combined with IS. Larger studies are needed to confirm if ITI with the IS-protocols is more effective with less complications.