Hematopoietic cell transplantation in the twitcher mouse: The effects of pretransplant conditioning with graded doses of busulfan

The effects of congenic hematopoietic cell transplantation (HCT; transplantation of bone marrow and spleen cells) after graded doses of busulfan (BU), a myeloablative but nonimmunosuppressive alkylating agent, were evaluated in the twitcher mouse model of human galactosylceramidase deficiency, a demyelinating sphingolipid storage disease. C57BL/6 twitcher mice (immunophenotype Ly-5.1) were given 10 to 50 mg/kg of BU or total-body irradiation (9.0 Gy) at age nine days and HCT from congenic Ly-5.2 donors 24 hr later. The 30-day post-HCT survival, an indicator of tolerance of the preparative regimen, was at least 83% in twitcher mice given 45 mg/kg or less of BU, was 50% in recipients of 50 mg/kg BU and 75% in TBI-conditioned twitchers