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Biol Blood Marrow Transplant. 2003 Aug;9(8):489-95.

Postgrafting immunosuppression with sirolimus and cyclosporine facilitates stable mixed hematopoietic chimerism in dogs given sublethal total body irradiation before marrow transplantation from DLA-identical littermates.

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Program in Transplantation Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.


We studied the value of postgrafting immunosuppression with sirolimus (SRL) and cyclosporine (CSP) in enhancing engraftment of dog leukocyte antigen-identical littermate marrow after nonmyeloablative conditioning in a canine model. Dogs received either 2 Gy (n=7) or 1 Gy (n=5) total body irradiation (TBI), followed by postgrafting immunosuppression with SRL and CSP. In the first cohort, all 7 dogs showed rapid initial engraftment. One engrafted dog died on day 21 due to hemorrhagic pneumonitis. Durable engraftment was seen in 5 of 6 remaining dogs, with a median follow-up of >48 (range, >32 to >56) weeks. The sixth dog rejected the marrow graft (as assessed by variable number of tandem repeats) at 11 weeks; however, a subsequent skin graft from the same marrow donor did not undergo acute cellular rejection, suggesting donor-specific tolerance. In the second cohort, all 5 dogs rejected the marrow graft at a median of 9 weeks (range, 3-11 weeks). We conclude that SRL/CSP is as effective as a previously studied combination of mycophenolate mofetil and CSP at establishing durable marrow engraftment after sublethal conditioning.

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