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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sublethally (600 R) irradiated (CBA x C57BL)F(1) mice were grafted intravenously with parental lymph node cells in doses ranging from 0.2 x 10(6) to 12 x 10(6). The transplantation of these lymphoid cells leads to inactivation of the recipient's endogenous CFU (as measured by the diminution of the number of colonies registered on the 10th day after irradiation). A 50% inactivation was observed when the graft size of the CBA cells was 0.52 x 10(6). This figure for C57BL cells was 10 times more. This experimental system evaluates two simultaneously developing processes: the multiplication of endogenous CFU and the homograft reaction of transplanted lymphocytes against them. Both processes can be quantitatively estimated simultaneously in the same experiment by the determination of the number of colonies in corresponding experimental groups. Thus it was possible in a single experiment to compare quantitatively the effect of immunosuppressants on two points: (a) mitostatic action (suppression of CFU) and (b) lymphotoxic action. The latter, a true immunosuppressive effect, represents suppression of GVH activity of lymphoid cells and is demonstrated by abolition of the inhibition of endogenous colony formation. In the present system we have tested 6-MP, ALS, cyclophosphamide, hydrocortisone, and other drugs. The definite mitostatic and lymphotoxic doses of drugs are ascertained. Cyclophosphamide and ALS proved to be drugs with high dose ranges of selective lymphotoxic action. Hydrocortisone acetate had a more narrow range of selective lymphotoxic effect. 6-MP and Imuran (azathioprine) failed to exert any selective action on lymphoid elements. They possessed pronounced mitostatic efficiency, however.
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PMID:An experimental system for the simultaneous estimation of mitostatic and lymphotoxic effects of immunosuppressants and cytostatics. 439 41

A foal with primary severe combined immunodeficiency, diagnosed within the first two weeks of life, was maintained with its dam in semi-isolation. The foal received continuous prophylactic antibiotic therapy, plasma from a sibling hyperimmunised with equine adenovirus vaccine, and intensive general nursing care. A full sibling female was selected as a bone marrow donor on the basis of red blood cell cross-matching and mixed lymphocyte reactions. Cyclophosphamide was given before two bone marrow transfusions at 35 and 73 days of age. To prevent graft versus host disease graft versus host disease the foal was maintained on methotrexate therapy. Reconstitution was not achieved nor were there signs of graft versus host disease. The foal died suddenly four days after the second bone marrow transfer when 77 days old. It had remained clinically free of any life threatening infectious disease and at necropsy a remarkable degree of freedom from infectious disease was confirmed. The most notable necropsy findings were bilateral nephrosis and myocardial degeneration and fibrosis. The likely cause of death was an electrolyte imbalance, particularly hypokalaemia, which secondarily affected the myocardium. Renal toxicity caused by the cytotoxic drugs, especially cyclophosphamide, may have contributed to the electrolyte imbalance.
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PMID:Attempted reconstitution of a foal with primary severe combined immunodeficiency. 634 83

A 16-year-old girl with severe aplastic anaemia was successfully treated with retransplantation of bone marrow from an HLA-identical sibling after rejection of the first transplantation from the same donor. Cyclophosphamide was used for the first transplantation and cyclophosphamide, 300 rad total-body irradiation and antilymphocyte globulin were used for the second transplantation. Permanent engraftment was achieved after the retransplantation with normalization of haemopoiesis, which has lasted for over 17 months. The patient is now in excellent clinical condition with minimal signs of chronic graft versus host disease.
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PMID:A case of severe aplastic anaemia successfully treated by retransplantation from the same donor. 675 8

A newborn with graft-vs-host (GVH) disease following an exchange transfusion was treated by attempting to eradicate the incompatible graft and to reconstitute the child hematologically and immunologically with a bone marrow transplant. The patient was a female term infant (blood group B, Rh+ Coombs test positive) who received a one-unit group O, Rh- exchange transfusion from an unrelated female donor for hyperbilirubinemia due to ABO incompatibility on day 2. Signs of acute GVH disease began on day 8 and the clinical diagnosis was supported by skin biopsy. With antithymocyte globulin and high dose dexamethasone, the GVH reaction improved somewhat. Cyclophosphamide, 200 mg/kg total dose, was given over four days followed by a marrow graft from a brother who was HLA-A, B identical, and probably also D locus compatible in mixed lymphocyte culture. All signs of GVH resolved with cyclophosphamide treatment and hematologic reconstitution was evident by 14 days after transplant. Two weeks later the GVH reaction and aplastic anemia recurred and Y chromatin was detected in only 6% of marrow cells. The infant died on day 80. Autopsy showed disseminated candidiasis, disseminated cytomegalovirus infection, thymic dysplasia, hypoplastic marrow, and other histopathologic changes consistent with GVH disease. The persistence of female cells in blood and bone marrow and the destruction of the reconstituted marrow suggest that the original incompatible transfusion-derived graft was not eliminated and that it ultimately rejected the histocompatible marrow graft.
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PMID:Probable graft-vs-graft reaction in an infant after exchange transfusion and marrow transplantation. 680 70

Bone marrow transplantation from an HLA-identical sibling is increasingly used in the treatment of severe aplastic anemia. One major problem with this approach is graft rejection that occurs in 25%-60% of patients conditioned for transplantation with cyclophosphamide. At most transplant centers it has been difficult to accurately identify patients at high risk for graft rejection. We studied a conditioning regimen of cyclophosphamide (200 mg per kg) and low-dose total body irradiation (3 Gy; equivalent to 300 rad) in 23 consecutive unselected patients with aplastic anemia followed for a minimum of 6 mo. There was only one episode of graft rejection. Graft-versus-host disease and interstitial pneumonitis were not increased by the more intensive conditioning regimen. Actuarial survival was 61% at 1 yr and 49% at 2.5 yr. Cyclophosphamide and low-dose total body irradiation is an effective conditioning regimen in patients with aplastic anemia. It may be particularly useful when accurate predictive tests of graft rejection are not available as is the case in most transplant centers.
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PMID:Prevention of graft rejection following bone marrow transplantation. 700 32

This articles summarizes the experience of the Hospital Saint-Louis Bone Marrow Transplantation Team of bone marrow transplantation in severe aplastic anemia. Sixty-five consecutive patients have been transplanted with an HLA identical sibling marrow. Various conditioning regimen have been used. Conditioning regimen using high dose Cyclophosphamide alone or associated with Procarbazine and anti-thymocyte globulin gave a high number of bone marrow graft rejection. Therefore, a conditioning regimen using Cyclophosphamide and total body irradiation with lung shielding has been used for the last three years. This regimen suppressed bone marrow graft rejection. The main problems remain graft versus host disease and intercurrent infections. Despite these complications, 50 per cent of the patients become long term survivors and are apparently cured of their initial disease.
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PMID:Bone marrow transplantation in 65 patients with severe aplastic anemia. 701 71

Seventeen patients with relapsed, acute leukemia were grafted with bone marrow from HLA-identical siblings by the 'Munich Cooperative Group for Bone Marrow Transplantation' during the period from August 1975 to June 1980. The antileukemic and immunosuppressive conditioning treatment consisted of high doses of bischlorethyl nitrosourea, Cytosine-Arabinoside and Cyclophosphamide, as well as, total body irradiation of about 9 Gy (midline body dose) from dual 60Cobalt sources. Methotrexate was given to all patients for prophylaxis of graft-versus-host disease (GvHD). Nine patients received marrow that was treated with anti-T-cell globulin (ATCG) "in vitro".--Crossreacting antibodies against hemopoietic stem cells were removed by absorption. Two of 5 evaluable patients given untreated marrow developed chronic GvHD, while patients given ATCG-treated marrow did not show unequivocal symptoms of GvHD. Six patients are in complete remission one to 33 months following bone marrow transplantation (b.m.t.) Five patients died with relapses of leukemia between 3 1/2 and 24 months following b.m.t., 3 patients died with interstitial pneumonia within 3 months of b.m.t. and 3 patients died with insufficient graft function within 4 weeks of b.m.t. Four of thirteen patients that were grafted more than 6 months ago are presently alive and in continuous complete remission at 11, 14, 29 and 33 months following b.m.t. Our results confirm that longterm remissions can be obtained with b.m.t. in patients with acute leukemia in advanced stage.
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PMID:[Bone marrow transplantation for relapsed, acute leukaemia (author's transl)]. 701 3

From March 1975 until May 1980 twelve patients with severe aplastic anemia were grafted with bone marrow from HLA-identical siblings by the Munich Cooperative Group for Bone Marrow Transplantation. Six patients are alive between 10 months and more than 5 years after grafting with normal blood values and marrow. One patient is treated as an out patient for chronic localized graft-versus-host disease (GvHD), five patients are well and without treatment. Six patients have died, one patient with a cerebral hemorrhage the day before transplantation, three patients following rejection of grafts 32, 40 and 55 days after grafting, one patient with severe GvHD 85 days after grafting and one patient, probably with interstitial pneumonia, following cerebral hemorrhage. Three of 6 patients who were conditioned with Cyclophosphamide (CY) only died following rejection of the graft. Two adults who were conditioned with CY and "total lymphoid irradiation" and three children, who wer given unirradiated leukocyte concentrates from the marrow donor after grafting, did not reject their grafts. The results of the Munich-Cooperative Group for Bone Marrow Transplantation are comparable to those of large, specialized centers for bone marrow transplantation, they indicate possibilities of cure of severe aplastic anemia by marrow grafts from HLA-identical siblings. They confirm that better results are obtained with earlier transplantation in the course of the disease.
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PMID:[Bone marrow transplantation for aplastic anaemia (author's transl)]. 701 55

Murine graft versus host (GVH) disease takes two forms depending upon the parental/F1 strain combination employed. Acute lethal GVH disease is characterized by anemia, lymphopenia, hypogammaglobulinemia, profound anti-F1 cytotoxicity, and the loss of cytotoxic potential against third-party alloantigen. In contrast to this, chronic GVH disease is characterized by polyclonal B cell activation, autoantibody production, no anti-F1 cytotoxicity, and retained cytotoxicity against allotargets. We have previously reported that this marked disparity in disease expression results from a radiosensitive host cell which protects the F1 mouse from parental anti-F1 CTX in mice undergoing CGVH disease. Using an in vitro system to induce the host protective cell, we now demonstrate that two distinct Thy-1+ cells emerge which regulate CTX against the host. One cell is of host origin, radiation sensitive, and functionally resembles a veto cell. The second regulatory cell, of parental origin, is radiation resistant and restricted in its ability to suppress anti-F1 CTX. We further demonstrate that the emergence of these cells is modulated by competitive immunoregulatory influences mediated by T contrasuppressor and I-J+ cells.
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PMID:The host response in graft versus host disease. III. The in vitro induction of regulatory cells in chronic murine graft versus host disease. 763 39

Conditioning regimens for BMT are important in determining transplant outcome. A radiation-free protocol containing Mitobronitol (DBM), Cytarabine (Ara-C) and Cyclophosphamide (Cy) was used for conditioning of patients with chronic granulocytic leukemia (CGL). Using this conditioning treatment, fewer transplant related complications, including acute GVHD, VOD and severe infections, were observed. Acute GVHD did not develop, but chronic GVHD, accompanied with graft-versus leukemia, was present in half of the cases. To determine the clinical effect of the DBM/Ara-C/Cy conditioning, the recovery of peripheral blood lymphocytes was examined after allogeneic BMT for patients with CGL in comparison with TBI/Cy conditioning. The lymphocyte subsets of 11 DBM patients were followed and analyzed periodically (30-90 days, 4-12 months and > 13 months) using ten monoclonal antibodies and flow cytometry. Decreased percentage of total T cells as well as CD4+ and CD8+ subpopulations, significantly decreased T cell activation and increased proportion of TCR gamma delta + cells were found to be characteristic in the early post-transplant period in the DBM group. Early recovery and consistently higher percentage of B cells were observed for the whole follow-up period of patients receiving DBM conditioning. A high proportion of NK cells was observed in all transplant recipients. These findings suggest that the characteristic pattern of recovering lymphocytes is associated with the lack of severe transplant-related clinical complications following DBM/Ara-C/Cy conditioning.
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PMID:Lymphocyte subset reconstitution after allogeneic bone marrow transplantation using radiation-free conditioning regimen for patients with chronic granulocytic leukemia. 767 5


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