TY - JOUR
T1 - 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
AU - Hogan, William J.
AU - Little, Marie Térèse
AU - Zellmer, Eustacia
AU - Friedetzky, Anke
AU - Diaconescu, Razvan
AU - Gisburne, Serina
AU - Lee, Richard
AU - Kuhr, Christian
AU - Storb, Rainer
N1 - Funding Information:
Supported in part by grants CA78902 and CA15704 awarded by the National Institutes of Health, DHHS, Bethesda, MD. Additional support was provided by the Mayo Foundation Scholarship, Division of Hematology, Mayo Medical Center, Rochester, MN (W.H.), the Lady Tata Memorial Trust International Research Grant, London, UK (M.-T.L.), the Laura Landro Salomon Endowment Fund (R.S.), the Jose Carreras International Leukemia Foundation (R.S.), and a prize from the Josef Steiner Krebsstiftung, Bern, Switzerland (R.S.).
PY - 2003/8
Y1 - 2003/8
N2 - 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.
AB - 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.
KW - Engraftment
KW - Graft rejection
KW - Hematopoietic cell transplantation
UR - http://www.scopus.com/inward/record.url?scp=0346363060&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0346363060&partnerID=8YFLogxK
U2 - 10.1016/S1083-8791(03)00148-4
DO - 10.1016/S1083-8791(03)00148-4
M3 - Article
C2 - 12931117
AN - SCOPUS:0346363060
SN - 1083-8791
VL - 9
SP - 489
EP - 495
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 8
ER -