Engraftment of allogeneic bone marrow without graft-versus-host disease in mongrel dogs using total lymphoid irradiation
We achieved long-term engraftment of unmatched bone marrow (BM) in dogs without graft-versus-host disease (GVHD) using a regimen of total lymphoid irradiation (TLI) which could be applied clinically. Twelve normal adult mongrel dogs were given TLI in 18 fractions of 100 rad each (total dose, 1800 rad) over 4 weeks to mantle and abdominal fields in continuity. Nine of the 12 were transfused with one or two random donor whole blood transfusions during the irradiation regimen to determine the risk of sensitization after the onset of immunosuppression. A mean (+- SD) of 0.71 +- 0.54 x 10/sup 9/ BM cells/kg of recipient body weight from unrelated sex-mismatched donors was infused within 24 h of the 18th irradiation fraction. Engraftment was assessed by demonstration of donor-type sex chromosomes in spontaneous metaphase spreads of recipient marrow aspirates, and by the appearance of donor-type red blood cells antigens (DEA) in the recipients' blood. Three untransfused and nine transfused recipients were shown to be stable mixed BM chimeras during a followup period of 2 to 11 months after transplantation. Blood transfusion during TLI did not result in graft rejection. We observed no clinical signs of acute or chronic GVHD. TLI has minimal toxicity when compared with conditioning regimens currently used in BM transplantation for aplastic anemia. Potential advantages of the TLI regimen include the opportunity to use unmatched marrow donors and protection from GVHD.
- Research Organization:
- Stanford Univ., CA
- OSTI ID:
- 5246556
- Journal Information:
- Transplantation; (United States), Journal Name: Transplantation; (United States) Vol. 29:6; ISSN TRPLA
- Country of Publication:
- United States
- Language:
- English
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560152* -- Radiation Effects on Animals-- Animals
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTIGENS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BODY
BONE MARROW
DOGS
EXTERNAL IRRADIATION
GRAFT-HOST REACTION
HEMATOPOIETIC SYSTEM
IMMUNOSUPPRESSION
INHIBITION
IRRADIATION
LYMPHATIC SYSTEM
MAMMALS
ORGANS
PARTIAL BODY IRRADIATION
RADIATION EFFECTS
RADIOINDUCTION
TISSUES
TRANSPLANTS
VERTEBRATES