Tail clip survival test assessing phenotypic correction of hemophilia A mice with preexisting immunity. (A) The effect of inhibitor titer on phenotypic correction. Immunized FVIII^null mice were conditioned with either 1100 cGy or 660 cGy TBI and received BM cells from 2bF8^tg+/− Mice. After allowing 1-month BM reconstitution, tail clip survival tests were performed to assess phenotypic correction, and the percentage of animals that survived beyond 24 hours was determined. Data shown are summarized from 9 BM transplantation trials. (B) The effect of conditioning regimens on phenotypic correction. Immunized FVIII^null mice were conditioned with a myeloablative regimen (1100 cGy TBI) or various nonmyeloablative conditions (660, 440, or 220 cGy TBI) and received BM transplantation from 2bF8^tg+/− mice. After 1-month BM reconstitution in the groups conditioned with 1100 cGy or 660 cGy and 2 months in the groups with 440 cGy or 220 cGy, phenotypic correction was assessed by tail clip survival test, and the percentage of animals that survived beyond 24 hours was determined. Data shown are summarized from 10 BM transplantation trials. These results demonstrate that transplantation of 2bF8 genetically modified HSCs can restore hemostasis to hemophilic mice with preexisting immunity.