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.