Cyclosporin A and methotrexate in canine marrow transplantation: engraftment, graft-versus-host disease, and induction of intolerance
We examined the effect of methotrexate (MTX) and cyclosporin A (Cy A) on engraftment, graft-versus-host disease (GVHD), and the induction of tolerance in dogs prepared for marrow transplantation by 9 Gy of total body irradiation and grafted with bone marrow and buffy coat cells. Nineteen dogs were given grafts from DLA-identical littermates followed by immunosuppression with Cy A for 25 or 100 days. All had sustained engraftment, and 12 became healthy long-term chimeras. Sixty dogs were given grafts from DLA-nonidentical unrelated donors. Among nine given MTX only postgrafting, one rejected the graft nd eight died with GVHD. Among 18 dogs given Cy A only postgrafting, eight failed to achieve engraftment, seven died of various causes, and three died with GVHD. Thirty-four dogs were given both MTX and Cy A in various regimens postgrafting. The only long-term survivors were 4 of 10 dogs given MTX on days 1, 3, 6, and 11 and Cy A from days 0 through 100. Two have chronic GVHD. We conclude that Cy A can induce graft-host tolerance across minor, but not major, histocompatibility differences. The combination of MTX early after transplantation with Cy A prevents failure of engraftment of histoincompatible marrow and some recipients become long-term survivors.
- Research Organization:
- Fred Hutchinson Cancer Research Center, Seattle, Washington
- OSTI ID:
- 6579490
- Journal Information:
- Transplantation; (United States), Journal Name: Transplantation; (United States) Vol. 34:1; ISSN TRPLA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560152* -- Radiation Effects on Animals-- Animals
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL TISSUES
ANIMALS
ANTIMETABOLITES
ANTIMITOTIC DRUGS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
BONE MARROW
CHIMERAS
DOGS
DRUGS
EXTERNAL IRRADIATION
GRAFT-HOST REACTION
HEMATOPOIETIC SYSTEM
IMMUNOSUPPRESSION
IMMUNOSUPPRESSIVE DRUGS
IRRADIATION
LEUKOCYTES
MAMMALS
MATERIALS
METHOTREXATE
MOSAICISM
ORGANS
TISSUES
TRANSPLANTS
VERTEBRATES
WHOLE-BODY IRRADIATION