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Title: Engraftment of DLA-nonidentical unrelated canine marrow after high-dose fractionated total body irradiation

Abstract

Marrow transplants were carried out between unrelated DLA-nonidentical dogs. Recipients were conditioned for transplantation by total body irradiation (TBI) given either as a single dose of 9 Gy (900 rad) or fractionated in three increments of 6 Gy (600 rad) each at intervals of 48 hr. All recipients received marrow, less than or equal to to 4 X 10/sup 8/ cells/kg, and no buffy coat cells. No immunosuppression was given after grafting. All 10 dogs given single-dose total body irradiation failed to show engraftment and died with marrow aplasia and infectious complications (median survival 12 days). In contrast, all 10 dogs given fractionated TBI had sustained engraftment and died with graft-versus-host disease (GVHD) and infectious complications (median survival 12.5 days). None of the dogs died from radiation-induced gastroenteritis.In conclusion, resistance to DLA-nonidentical unrelated marrow grafts can be abrogated by high-dose TBI. This technique may allow hemopoietic engraftment even after in vitro manipulation of the marrow such as lymphocyte depletion by cell separation or treatment with anti-T cell antisera.

Authors:
 [1]; ; ; ; ;
  1. (Fred Hutchinson Cancer Research Center, Seattle, WA)
Publication Date:
OSTI Identifier:
7066015
Resource Type:
Journal Article
Resource Relation:
Journal Name: Transplantation; (United States); Journal Volume: 33:4
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 59 BASIC BIOLOGICAL SCIENCES; BONE MARROW; TRANSPLANTS; IMMUNITY; BIOLOGICAL RADIATION EFFECTS; IMMUNOSUPPRESSION; RADIOINDUCTION; BLOOD COUNT; COBALT 60; DOGS; FRACTIONATED IRRADIATION; GAMMA RADIATION; GRAFT-HOST REACTION; INFECTIOUS DISEASES; WHOLE-BODY IRRADIATION; ANIMAL TISSUES; ANIMALS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOLOGICAL EFFECTS; BODY; COBALT ISOTOPES; DISEASES; ELECTROMAGNETIC RADIATION; EXTERNAL IRRADIATION; HEMATOPOIETIC SYSTEM; INTERMEDIATE MASS NUCLEI; INTERNAL CONVERSION RADIOISOTOPES; IONIZING RADIATIONS; IRRADIATION; ISOMERIC TRANSITION ISOTOPES; ISOTOPES; MAMMALS; MINUTES LIVING RADIOISOTOPES; NUCLEI; ODD-ODD NUCLEI; ORGANS; RADIATION EFFECTS; RADIATIONS; RADIOISOTOPES; TISSUES; VERTEBRATES; YEARS LIVING RADIOISOTOPES; 560152* - Radiation Effects on Animals- Animals; 551000 - Physiological Systems

Citation Formats

Deeg, H.J., Storb, R., Shulman, H.M., Weiden, P.L., Graham, T.C., and Thomas, E.D. Engraftment of DLA-nonidentical unrelated canine marrow after high-dose fractionated total body irradiation. United States: N. p., 1982. Web. doi:10.1097/00007890-198204000-00021.
Deeg, H.J., Storb, R., Shulman, H.M., Weiden, P.L., Graham, T.C., & Thomas, E.D. Engraftment of DLA-nonidentical unrelated canine marrow after high-dose fractionated total body irradiation. United States. doi:10.1097/00007890-198204000-00021.
Deeg, H.J., Storb, R., Shulman, H.M., Weiden, P.L., Graham, T.C., and Thomas, E.D. Thu . "Engraftment of DLA-nonidentical unrelated canine marrow after high-dose fractionated total body irradiation". United States. doi:10.1097/00007890-198204000-00021.
@article{osti_7066015,
title = {Engraftment of DLA-nonidentical unrelated canine marrow after high-dose fractionated total body irradiation},
author = {Deeg, H.J. and Storb, R. and Shulman, H.M. and Weiden, P.L. and Graham, T.C. and Thomas, E.D.},
abstractNote = {Marrow transplants were carried out between unrelated DLA-nonidentical dogs. Recipients were conditioned for transplantation by total body irradiation (TBI) given either as a single dose of 9 Gy (900 rad) or fractionated in three increments of 6 Gy (600 rad) each at intervals of 48 hr. All recipients received marrow, less than or equal to to 4 X 10/sup 8/ cells/kg, and no buffy coat cells. No immunosuppression was given after grafting. All 10 dogs given single-dose total body irradiation failed to show engraftment and died with marrow aplasia and infectious complications (median survival 12 days). In contrast, all 10 dogs given fractionated TBI had sustained engraftment and died with graft-versus-host disease (GVHD) and infectious complications (median survival 12.5 days). None of the dogs died from radiation-induced gastroenteritis.In conclusion, resistance to DLA-nonidentical unrelated marrow grafts can be abrogated by high-dose TBI. This technique may allow hemopoietic engraftment even after in vitro manipulation of the marrow such as lymphocyte depletion by cell separation or treatment with anti-T cell antisera.},
doi = {10.1097/00007890-198204000-00021},
journal = {Transplantation; (United States)},
number = ,
volume = 33:4,
place = {United States},
year = {Thu Apr 01 00:00:00 EST 1982},
month = {Thu Apr 01 00:00:00 EST 1982}
}
  • Marrow transplants were carried out between unrelated DLA-nonidentical dogs. Recipients were conditioned for transplantation by total body irradiation (TBI) given eigher as a single dose of 9 Gy (900 rad) or fractionated in three increments of 6 Gy (600 rad) each at intervals of 48 hr. All recipients received marrow, less than or equal to 4 x 10(8) cells/kg, and no buffy coat cells. No immunosuppression was given after grafting. All 10 dogs given single dose total body irradiation failed to show engraftment and died with marrow aplasia and infectious complications (median survival 12 days). In contrast, all 10 dogsmore » given fractionated TBI had sustained engraftment and died with graft-versus-host disease (GVHD) and infectious complications (median survival 12.5 days). None of the dogs died from radiation-induced gastroenteritis. In conclusion, resistance to DLA-nonidentical unrelated marrow grafts can be abrogated by high-dose TBI. This technique may allow hemopoietic engraftment even after i vitro manipulation of the marrow such as lymphocyte depletion by cell separation or treatment with anti-T cell antisera.« less
  • The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing [sup 60]Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionatedmore » total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs.« less
  • The marrow matrix of total-body x-irradiated dogs (1200 R midline dose) was able to support effective hemopoiesis for several hundred days if the animals were transfused with their own mononclear leukocytes collected from the blood prior to irradiation and preserved at ultralow temperatures. However, a lesion developed in the marrow, consisting of a fibrosis originating in conjunction with or from the endosteum. The fibrotic tissue substantially reduced the available marrow space in dogs with advanced lesions. The number of autologous, cryopreserved mononuclear leukocytes transfused ranged from 0.32 x 10(9) to 1.63 x 10(9)/kg body weight. The observation period extended tomore » a maximum of 898 days after irradiation.« less
  • Bone marrow transplants with low marrow cell doses (less than or equal to4 X 10/sup 8/ cells/kg) from unrelated donors were carried out in 16 dogs conditioned with 9 Gy (900 rad) of total body irradiation. No immunosuppression was given after grafting. Eleven donor-recipient pairs were phenotypically identical (group 1) for the known antigens of the canine major histocompatibility complex (DLA) and in five the donor was homozygous and the recipient heterozygous for DLA (group 2), as determined by serological histocompatibility typing and mixed leukocyte cultures including homozygous cell typing. In addition, lymphocytes from donors and recipients in group 1more » were mutually nonreactive in cell-mediated lympholysis; lymphocytes from recipients in group 2 were not cytotoxic against donor cells. Eight dogs rejected their grafts and eight showed sustained engraftment; of these, four died from graft-versus-host disease. The incidence of rejection was higher than in DLA-identical littermates but lower than in DLA-nonidentical unrelated or littermate dogs. These results indicate that antigens different from the recognized alleles at DLA are involved in the control of engraftment. These antigens most likely represent the expression of unrecognized differences within DLA or are coded for by a locus different from but linked to DLA-A, B, C or D; they are not recognized in the cell-mediated lympholysis assay.« less
  • We describe the clinical course of a 16 year old girl with aplastic anemia who was treated by syngeneic bone marrow transplantation. Engraftment was not obtained by simple infusion of bone marrow without immunosuppression. The patient received a high-dose cyclophosphamide and thoracoabdominal irradiation, followed by second marrow transplantation from the same donor. Incomplete but significant hematologic recovery was observed; however, marrow failure recurred 5 months after transplantation. Since donor and recipient pairs were genotypically identical, graft failure could not be attributed to immunological reactivity of recipient cells to donor non-HLA antigens. This case report implies that graft failure in somemore » cases of aplastic anemia might be mediated by inhibitory cells resistant to cyclophosphamide and irradiation.« less