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

William J. Hogan, Marie Térèse Little, Eustacia Zellmer, Anke Friedetzky, Razvan Diaconescu, Serina Gisburne, Richard Lee, Christian Kuhr, Rainer Storb

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)489-495
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume9
Issue number8
DOIs
StatePublished - Aug 1 2003

Keywords

  • Engraftment
  • Graft rejection
  • Hematopoietic cell transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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