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 Blood, 1 July 2007, Vol. 110, No. 1, pp. 418-423.
Prepublished online as a Blood First Edition Paper on March 16, 2007; DOI 10.1182/blood-2007-02-071282.

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TRANSPLANTATION

Stable trichimerism after marrow grafting from 2 DLA-identical canine donors and nonmyeloablative conditioning

Scott S. Graves1, William Hogan1, Christian S. Kuhr1,2, Razvan Diaconescu1, Michael A. Harkey1, George E. Georges1,2, George E. Sale1,2, Eustacia Zellmer1, Szczepan Baran1, Christoph Jochum1, Brad Stone3, and Rainer Storb1,2

1 Fred Hutchinson Cancer Research Center 2 University of Washington School of Medicine 3 Benaroya Research Institute, Seattle, WA

Although hematopoietic cell transplantation (HCT) is generally accomplished using a single donor, multiple donors have been used to enhance the speed of engraftment, particularly in the case of umbilical cord blood grafts. Here we posed the question in the canine HCT model whether stable dual-donor chimerism could be established using 2 DLA-identical donors. We identified 8 DLA-identical littermate triplets in which the marrow recipients received 2 Gy total body irradiation followed by marrow infusions from 2 donors and postgrafting immunosuppression. All 8 dogs showed initial "trichimerism," which was sustained in 5 dogs, while 2 dogs rejected one of the allografts and remained mixed chimeras, and 1 dog rejected both allografts. Immune function in one trichimeric dog, as tested by mixed leukocyte culture response and antibody response to sheep red blood cells, was found to be normal. Five dogs received kidney grafts from one of their respective marrow donors at least 6 months after HCT without immunosuppressive drugs, and grafts in 4 dogs are surviving without rejection. In summary, following nonmyeloablative conditioning, simultaneous administration of marrow grafts from 2 DLA-identical littermates could result in sustained trichimerism, and immunologic tolerance could include a kidney graft from one of the marrow donors.


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