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Blood, Vol. 94 No. 3 (August 1), 1999:
pp. 1131-1136
Stable Mixed Hematopoietic Chimerism in Dog Leukocyte
Antigen-Identical Littermate Dogs Given Lymph Node Irradiation Before
and Pharmacologic Immunosuppression After Marrow Transplantation
Rainer Storb,
Cong Yu,
Todd Barnett,
John L. Wagner,
H. Joachim Deeg,
Richard A. Nash,
Hans-Peter Kiem,
Peter McSweeney,
Kristy Seidel,
George Georges, and
J. Maciej Zaucha
From the Clinical Research Division and Public Health Sciences
Division, Fred Hutchinson Cancer Research Center; Department of
Medicine, University of Washington; and Swedish Medical Center Tumor
Institute, Seattle, WA.
Stable mixed donor/host hematopoietic chimerism can be accomplished
in dog leukocyte antigen (DLA)-identical littermate dogs given
sublethal (200 cGy) total-body irradiation (TBI) before and
immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP) after transplant (Blood 89:3048, 1997). Studies were
based on the hypothesis that drugs that prevent graft-versus-host
disease (GVHD) after transplant also suppress host-versus-graft (HVG) reactions and thereby enhance engraftment. Here, we asked whether pretransplant TBI provided marrow space for the graft to home or caused
host immunosuppression. To address the questions, recipients were given
pretransplant irradiation to cervical, thoracic, and abdominal lymph
nodes (except pelvis), DLA-identical littermate marrow grafts, and
MMF/CSP posttransplant. Six dogs that received 450 cGy irradiation
showed initial engraftment. Two rejected their grafts after 8 and 18 weeks, 1 died with GVHD and engraftment, and 3 are alive as mixed
chimeras after 57 to 97 weeks. Four dogs given 200 cGy irradiation also
showed initial engraftment, but rejected their grafts after 10 to 18 weeks. Mixed chimerism was present in nonirradiated marrow and lymph
node spaces and involved granulocytes, T cells, and monocytes. While
other explanations are possible, results seem consistent with the
hypothesis that pretransplant radiation provides host
immunosuppression, and grafts can create their own marrow space. These
data set the stage for the development of novel transplant regimens
that substitute immunosuppressive for cytotoxic agents.
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