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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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Submitted February 1, 2007
Accepted March 7, 2007

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

Scott S Graves*, William J Hogan, Christian S. Kuhr, Razvan Diaconescu, Michael A Harkey, George E Georges, George E Sale, Eustacia Zellmer, Szczepan Baran, Christoph Jochum, Brad Stone, and Rainer Storb

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
Clinical Research Division, University of Washington School of Medicine, Seattle, WA, United States

* Corresponding author; email: sgraves{at}fhcrc.org.

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 two 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 two 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 one 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 four dogs are surviving without rejection. In summary, following nonmyeloablative conditioning, simultaneous administration of marrow grafts from two DLA-identical littermates could result in sustained trichimerism and immunological tolerance could include a kidney graft from one of the marrow donors.


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