Low-dose immune tolerance induction alone or with immunosuppressants according to prognostic risk factors in Chinese children with hemophilia A inhibitors.

BACKGROUND

In developing countries, children with hemophilia A (HA) with high-titer inhibitor and poor immune tolerance induction (ITI) prognostic risk(s) cannot afford the recommended high- or intermediate-dose ITI.

OBJECTIVES

To determine the efficacy of low-dose ITI (plasma-derived factor VIII [FVIII]/von Willebrand factor at 50 FVIII IU/kg every other day) by itself (ITI-alone) or combined with immunosuppressants rituximab and prednisone (ITI-IS) in children with HA with high-titer inhibitor.

METHODS

All enrolled patients had pre-ITI inhibitor ≥10 BU. We used ITI-alone if inhibitor titer was <40 BU pre-ITI and during ITI, and ITI-IS if titer was ≥100 BU (historic) or ≥40 BU (pre- or during ITI) or if the patient was nonresponsive on ITI-alone.

RESULTS

Fifty-six children were analyzable, with median historic peak inhibitor titer 48.0 BU and followed for median 31.4 months. Overall, 35 (62.5%) achieved phase 2 success with negative inhibitor and normal FVIII recovery. The phase 2 success rate was 95% for the 20 patients receiving ITI-alone. For the 36 patients receiving ITI-IS, the phase 2 success rate was 44.4%, but would increase to 63.6% if the 14 patients with historic peak inhibitor titer ≥100 BU (and having phase 2 success rate of only 14.3%) were excluded. One patient developed repeated infection after IS treatment. Relapse occurred in 11.4% (4/35) patients with phase 2 success associated with rapid ITI dose reduction or irregular post-ITI FVIII prophylaxis. Our strategy reduced the cost from high-dose ITI by 74% to 90%.

CONCLUSION

The use of low-dose ITI with or without immunosuppressants according to ITI prognostic risk(s) is a clinically and economically feasible strategy for eradicating inhibitors in children with HA, particularly for those with historic peak inhibitor titer <100 BU.