Low-dose immune tolerance induction for children with hemophilia A with poor-risk high-titer inhibitors: A pilot study in China

Zekun Li; Zhenping Chen; Xiaoling Cheng; Xinyi Wu; Gang Li; Yingzi Zhen; Siyu Cai; Man-Chiu Poon; Runhui Wu

doi:10.1002/rth2.12248

Low-dose immune tolerance induction for children with hemophilia A with poor-risk high-titer inhibitors: A pilot study in China

Res Pract Thromb Haemost. 2019 Aug 9;3(4):741-748. doi: 10.1002/rth2.12248. eCollection 2019 Oct.

Authors

Zekun Li¹, Zhenping Chen¹, Xiaoling Cheng¹, Xinyi Wu¹, Gang Li¹, Yingzi Zhen¹, Siyu Cai², Man-Chiu Poon³, Runhui Wu¹

Affiliations

¹ Hemophilia Work Group Hematology Oncology Center Beijing Children's Hospital Affiliated to Capital Medical University Beijing China.
² Epidemiology Department Beijing Children's Hospital Affiliated to Capital Medical University Beijing China.
³ Departments of Medicine, Pediatrics and Oncology University of Calgary Cumming School of Medicine, and Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program Foothills Hospital Alberta Health Services Calgary Alberta Canada.

Abstract

Background: Immune tolerance induction (ITI) therapy is currently unaffordable in China. Management of hemophilia A children with high-titer inhibitor is therefore a challenge.

Aim: To describe the ITI strategy using plasma-derived factor VIII/von Willebrand factor concentrate (pdFVIII/VWF) +/- immunosuppression and to report its efficacy in children with hemophilia A having poor-risk status for ITI success.

Methods: A prospective pilot study on children with hemophilia A having poor-risk status (all with at least inhibitor titer > 10 BU pre-ITI initiation). Patients received ~50 IU/kg FVIII every other day using domestic intermediate purity pdFVIII/VWF products, either alone or in combination with rituximab +/- prednisone.

Results: Sixteen patients with median age 2.9 (range, 2.2-13.2) years and median pre-ITI inhibitor titer 30.7 (range, 10.4-128) BU were enrolled. Analysis at median 14.7 (range, 12.4-22.6) months' follow-up showed a total response rate of 87.5%. This included success (achieving inhibitor < 0.6 BU) in 13 patients (81.3%) in a median of 8.8 (range, 3.2-11.8) months, and partial success (achieving inhibitor < 5 BU but > 0.6BU) in 1 (6.3%). Compared to the pre-ITI period, the mean bleeds/month during ITI was 0.51 (64.0% reduction), and joint bleeds/month was 0.34 (64.3% reduction). This low-dose ITI strategy cost less by 70% to 87% than that for the high-dose FVIII regimen. No severe adverse events were observed.

Conclusion: This low-dose ITI strategy of pdFVIII/VWF +/- immunosuppression achieved relatively satisfactory outcomes in children with hemophilia A inhibitor having poor-risk status. This low-dose regimen showed economic advantages and is therefore suitable for using in China. However, further study in a larger cohort with a longer follow-up time is needed.

Keywords: child; hemophilia A; immune tolerance induction; immunosuppression; pilot projects; rituximab.