BACKGROUND: The ability to achieve significant donor engraftment without fully myeloablative conditioning has revolutionized
allogeneic stem cell transplantation. These nonmyeloablative approaches may allow extension of this potentially curative modality to an increasing number of patients including those with non-malignant diseases. Although a number of regimens have been explored, the optimal
means of conditioning has not been determined. METHODS: We previously demonstrated that
rapamycin (RAPA) has the ability to promote
T-cell tolerance even in the presence of
costimulation. In the current study, we examine the ability of
rapamycin or the
calcineurin inhibitor cyclosporine A (CSA) to promote chimerism in a murine haploidentical
bone marrow transplantation model.
Mice were conditioned with 300 cGy and received either RAPA at 3 mg/kg/day IP, CSA at 20 mg/kg/day IP, or no
immunosuppression starting on the day before the transplant and continued for 4 weeks. RESULTS: There was no apparent
toxicity, and animals maintained normal
blood counts throughout. More importantly, long-term macrochimerism was observed only in the RAPA-treated group. CONCLUSIONS: These results establish a simple,
nontoxic, irradiation-based regimen that facilitates engraftment without
ablation. This strategy may prove useful in nonmalignant disorders such as
hemoglobinopathies in which moderate levels of donor chimerism could prove curative.
