Immune tolerance induction with recombinant factor VIII in hemophilia A patients with high responding inhibitors.
Immune tolerance induction (ITI) eradicates inhibitors in patients with hemophilia A. This study was designed to investigate the success rate of ITI in high-responding inhibitor patients with severe hemophilia A using recombinant factor VIII (rFVIII). Twenty-six patients received different ITI regimens until a normal recovery (>66%) and half-life (>6 h) of infused FVIII was achieved. In order to maximize the chance of success, the initiation of ITI was deferred in the majority of patients until the inhibitor declined to <10 BU. Twenty-two patients (85%) had baseline inhibitor levels <10 BU (median 2.3 BU) when ITI began. Within a median of 6 months, immune tolerance was achieved in 19 of 26 patients (73%) including 12/17 (70%) with intron 22 inversion, 5/7 (71%) with other null mutations and two with small deletion/insertions in the F8 gene. In conclusion, recombinant FVIII induces a high rate of immune tolerance even in carriers of null F8 mutations.
Rocino
Angiola
A
Hemophilia and Thrombosis Center, Hematology Divisionn, San Giovanni Bosco Hospital, Naples, Italy. angiolar@tin.it
Santagostino
Elena
E
Mancuso
Maria Elisa
ME
Mannucci
Pier Mannuccio
PM
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects* / Q000235:genetics; D007223:Infant; D007518:Isoantibodies / Q000097:blood; D008875:Middle Aged; D009154:Mutation
D007518:Isoantibodies; C078147:F8 protein, human; D005169:Factor VIII