Mortality of Secondary Disease in Antibiotic-Treated Mouse Radiation Chimeras

Heit, H.; Wilson, Robert A.; Tm, Fliedner; Kohne, E.

doi:10.1016/b978-0-12-340650-7.50076-3

Cited by 22 publications

(11 citation statements)

References 2 publications

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“…Data obtained from the European Bone Marrow Transplant Registry for children (age < 15 years) grafted for severe aplastic anaemia between 1970 and 1980 (n = 71; comparable with the severe aplastic anaemia patients of this study) gave an overall transplantation-related mortality rate of 50 %, and a mortality rate due to bacterial or fungal infection of 14 % (A. Locasciulli, personal communication). The mortality rate due to transplantation-related complications for children and adolescents (age < 20 years) grafted for leukaemia and registered in (14)(15)(16)(17)(18). In man, the possible effect of GID on GvHD is controversial: several studies reported a reduction of the incidence of acute GvHD after allogeneic BMT (19,20,21).…”

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confidence: 98%

Prevention of infection and graft-versus-host disease by suppression of intestinal microflora in children treated with allogeneic bone marrow transplantation

Vossen

Heidt

Berg

et al. 1990

Eur. J. Clin. Microbiol. Infect. Dis.

114

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The effect of suppression with antimicrobial agents of the intestinal microflora of paediatric bone marrow graft recipients on severe bacterial and fungal infections and on moderate to severe acute graft-versus-host disease was studied retrospectively. Data on 65 cases of bone marrow transplantation for either severe bone marrow failure or leukaemia, performed in a strict protective environment with either complete or selective gastrointestinal decontamination, were evaluated. All bone marrow grafts were from HLA-identical siblings and were not depleted of T-lymphocytes. Twenty percent of the recipients had one or more episodes of septicaemia during the granulocytopenic period after transplantation, mostly due to gram-positive bacteria. Only five children died due to infection, in each case caused by a microorganism originating from the endogenous flora. Complete gastrointestinal decontamination was superior to selective gastrointestinal decontamination in preventing infectious complications (p less than 0.001). The same was the case for the prevention of acute graft-versus-host disease of grade II or higher, which was observed in 7 of 40 (17.5%) completely decontaminated children versus 9 of 18 (50%) selectively decontaminated children evaluable for graft-versus-host disease (p less than 0.01). It is concluded that complete gastrointestinal decontamination in a strict protective environment is a feasible and very effective method for preventing severe infections and acute graft-versus-host disease after allogeneic bone marrow transplantation in children and adolescents; it resulted in a low transplantation-related mortality of 26% and a good quality of survival in 69% of the graft recipients.

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mentioning

confidence: 98%

Prevention of infection and graft-versus-host disease by suppression of intestinal microflora in children treated with allogeneic bone marrow transplantation

Vossen

Heidt

Berg

et al. 1990

Eur. J. Clin. Microbiol. Infect. Dis.

114

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“…Intestinal pathology involving diarrhoea, malabsorption and enhanced epithelial permeability to luminal contents is thought to be a central component of the disease process [2,3]. In support of a role for gut microflora in the development of GVHD, animals kept under germ-free conditions or treated with antibiotics or antibodies to lipopolysaccharide (LPS) or endotoxin develop less severe GVHD [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Progressive Accumulation of Bacterial Lipopolysaccharide In Vivo During Murine Acute Graft‐Versus‐Host Disease

1997

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Price KS, Nestel FP, Lapp WS. Progressive Accumulation of Bacterial Lipopolysaccharide In Vivo During Murine Acute Graft-Versus-Host Disease. Scand J Immunol 1997;45:294-300 In a previous report the authors demonstrated that acute graft-versus-host disease (GVHD) was associated with pathologic amounts of tumour necrosis factor alpha (TNF-a) and the appearance of lipopolysaccharide (LPS) in the blood of GVH reactive mice just prior to death. In this study the authors have investigated the kinetics of LPS accumulation in different organs during the course of acute GVHD using a murine model. Unirradiated C57BL/6 × AF1 (B6AF 1 ) mice were transplanted with C57BL/6 (B6) lymphoid cells and killed at predetermined times after transplantation for LPS analysis. Control animals were injected with either 60 × 10 6 B6AF1 lymphoid cells (syngeneic) or 60 × 10 6 irradiated (2000 rad) CBA lymphoid cells (allogeneic). Lipopolysaccharide began to appear in the liver and the spleen of GVH reactive mice from day 2 post-transplant and by day 10 all GVH reactive mice tested positive for hepatic and splenic LPS. Low levels of LPS were detected in some control mice from days 2 to 10 post-transplant but LPS was never detected after day 10 in control groups. Total hepatic and splenic LPS in acute GVH reactive mice peaked at a time coincident with the appearance of LPS in the serum and with the onset of mortality. These results demonstrate that tissue levels of LPS increase throughout the course of acute GVHD and are sufficient to trigger the release of pathologic amounts of TNF-a from primed macrophages resulting in the cachexia and mortality associated with acute GVHD in this model.

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“…The mechanisms by which the "germ-free" environment decreases the incidence of GvHD remain conjectural. Mortality among lethally irradiated germ-free mice given H2 incompatible marrow transplants was significantly less than that among conventionally treated mice (Jones et al 1971, Heit et al 1973, van Bekkum et al 1974. It has been suggested that enteral bacteria sharing antigenic epitopes with mucosal epithelium are activating additional lymphocyte clones to react against gut epithelium, thereby increasing the mucosal damage.…”

Section: Opportunistic Infections In Acute Gvhdmentioning

confidence: 99%

Graft‐versus‐Host Disease in Dog and Man: The Seattle Experience

Storb

Thomas

1985

Immunological Reviews

153

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In dog and in man a marrow graft from a donor genetically identical for the major histocompatibility complex is followed by significant graft-versus-host disease (GvHD) in approximately one-half of the recipients, despite the administration of post-grafting immunosuppressive therapy. Controlled trials comparing post-grafting therapy using methotrexate or cyclosporine have shown no difference in long-term survival, although cyclosporine reduces the incidence of mucositis and is associated with somewhat earlier engraftment. Observations in the canine model indicating efficacy of a combination of a brief course of methotrexate with the cyclosporine regimen are now being tested in patients, with early results indicating a reduction in GvHD and an improved survival. In both species, failure to administer immunosuppression after grafting is associated with a high incidence of acute GvHD and an adverse effect on survival. Removal of donor T cells from the marrow inoculum may reduce the incidence of acute GvHD but at the price of a higher likelihood of subsequent graft failure. Studies of canine and human chimeras are in agreement with murine data indicating a principal role for T cells in the pathogenic mechanism of GvHD. Chimera lymphocytes (of donor origin) from dogs and patients with acute GvHD proliferate in response to previously stored host cells, and lymphocytes cytotoxic to host target cells are seen in patients with GvHD. Our observations indicate a direct, rather than an indirect, role for T cells since lymphocytes from donors sensitized to chimeric skin grafts can cause lethal GvHD when infused into stable chimeric recipients. "Specific" suppressor cells may play a role in maintaining stable graft-host tolerance while "nonspecific" suppressor cells may be responsible for the impaired immune defenses in patients with chronic GvHD. Chronic GvHD, which resembles systemic collagen vascular disease, occurs in approximately 40% of matched recipients, particularly following acute GvHD, and is more frequent in older patients. Efforts to treat both acute and chronic GvHD with steroids, antithymocyte globulin, cyclosporine and azathioprine are only partially and unpredictably effective. Data in dogs pointed out the feasibility of transplants from partially matched related donors or matched unrelated donors, an approach that is now being actively pursued in human patients. Marrow transplants from HLA-partially matched family members resulted in a higher incidence of acute GvHD.(ABSTRACT TRUNCATED AT 400 WORDS)

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Mortality of Secondary Disease in Antibiotic-Treated Mouse Radiation Chimeras

Cited by 22 publications

References 2 publications

Prevention of infection and graft-versus-host disease by suppression of intestinal microflora in children treated with allogeneic bone marrow transplantation

Prevention of infection and graft-versus-host disease by suppression of intestinal microflora in children treated with allogeneic bone marrow transplantation

Progressive Accumulation of Bacterial Lipopolysaccharide In Vivo During Murine Acute Graft‐Versus‐Host Disease

Graft‐versus‐Host Disease in Dog and Man: The Seattle Experience

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