Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

We analysed the incidence of graft failure, graft-versus-host disease (GVHD) and relapse of leukaemia in 208 patients undergoing allogeneic bone marrow transplantation (BMT) for chronic myeloid leukaemia in chronic phase in eight transplant centres in Europe and the United States. 106 patients received unmanipulated donor bone marrow (Group 1) and 102 patients received marrow depleted of T-cells by incubation with the monoclonal antibodies Campath-1 or CT-2 and complement (Group 2). The incidence of graft failure was higher and of GVHD was lower in Group 2 than in Group 1. Relapse of leukaemia occurred more frequently in patients in Group 2 than in Group 1 (17 v. 2, P less than 0.001). Multivariate analysis showed that the following factors were associated with an increased risk of relapse: the use of T-cell depletion, the absence of GVHD and a high platelet count at the time of admission for transplant. The findings support the concept that a graft-versus-leukaemia effect mediated by T-lymphocytes is important for cure of leukaemia after BMT.
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PMID:Bone marrow transplantation for chronic myeloid leukaemia in first chronic phase: importance of a graft-versus-leukaemia effect. 329 30

The infectious complications of bone marrow transplantation were reviewed in 43 adults, 22 of whom received transplants from HLA-matched donors without T-cell depletion and 21 of whom received donor marrow pretreated with the murine anti-T-cell monoclonal antibody CT-2 and complement. Recipients of HLA-mismatched, T-cell-depleted transplants had a higher rate of bacteremia (1.33 compared with 0.64 per patient, p = 0.05) and especially systemic fungal infections (0.92 compared with 0.14 per patient, p less than 0.001) than recipients of transplants from HLA-identical donors without T-cell depletion; two thirds of these infections occurred during the granulocytopenic period early after transplantation. Recipients of HLA-identical but T-cell-depleted transplants also had significantly more systemic fungal infections (0.77 per patient, p less than 0.001). T-cell depletion was associated with delayed engraftment, more prolonged granulocytopenia, and more severe lymphopenia and was shown by stepwise multivariate regression analysis to be the most powerful predictor of systemic fungal infection (r = 0.512, p less than 0.0001). Whereas ex-vivo T-cell depletion may reduce the risk of severe graft-versus-host disease, it may predispose the patient to infection, especially with fungi.
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PMID:Infectious complications in adults with bone marrow transplantation and T-cell depletion of donor marrow. Increased susceptibility to fungal infections. 351 42

The effects of ex-vivo depletion of T lymphocytes from donor bone marrow using a monoclonal anti-T-cell antibody (CT-2) and complement on the outcome of allogeneic bone marrow transplantation was evaluated in a prospective, randomized, double-blind study of 40 patients with leukemia. Patients receiving T-cell-depleted bone marrow had a lower incidence of acute graft-versus-host disease than control patients (3 of 20 compared with 13 of 20; p = 0.004), and mortality due to acute graft-versus-host disease was reduced. Five patients in the T-cell-depletion group developed graft failure; all control patients had sustained engraftment (p less than 0.05). Clinically apparent relapse of leukemia occurred in 7 patients from the T-cell-depletion group and in 2 controls (p, not significant). Cytogenetic evidence of residual leukemia was also detected in the 5 patients with graft failure without overt relapse. Infections and overall survival were similar in the two groups. The effects of T-cell depletion on engraftment and recurrence of leukemia require further evaluation.
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PMID:Treatment of donor bone marrow with monoclonal anti-T-cell antibody and complement for the prevention of graft-versus-host disease. A prospective, randomized, double-blind trial. 352 27

Histocompatible bone marrow transplantation is the treatment of choice for patients with severe combined immunodeficiency (SCID). Patients without histocompatible donors have been treated with a variety of nontransplant therapies; however, normal immunocompetence has not been achieved. Bone marrow transplantation with untreated histoincompatible bone marrow has resulted in fatal graft-versus-host disease and/or no lymphoid engraftment. Based upon murine experiments, the use of monoclonal antibody- and complement-treated parental bone marrow has been used to successfully transplant SCID patients. Monoclonal antibodies to a variety of T-lymphocyte differentiation antigens (OKT-3, T-12, CT-2, and Leu-1) have been used. The antibody-treated transplants differ in several important respects from histocompatible transplants for SCID. Many recipients for treated marrow grafts require immunosuppression. In certain cases, hematopoietic stem cell ablation with total body irradiation (TBI) or busulfan has been required to achieve stable lymphoid engraftment although the biological basis for the requirement for hematopoietic stem cell elimination is unclear. The use of antibody-treated parental bone marrow is the most effective form of therapy for patients with SCID who do not have a histocompatible donor.
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PMID:Antibody-treated bone marrow transplantation for patients with severe combined immune deficiency. 352 67

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality following bone marrow transplantation. The in vitro removal of the GVHD-causing T-lymphocytes from donor marrow is one approach which could control this complication. Treatment of the donor bone marrow with lectins and erythrocyte-forming rosette depletion, anti-T-cell antisera or monoclonal antibodies are methods currently being tested to accomplish this. CT-2 is an immunoglobulin monoclonal antibody specific for the T-cell erythrocyte-forming rosette receptor. Bone marrow from 23 consecutive donors was treated in vitro with CT-2 and complement, prior to infusion, as a potential means of controlling GVHD. Surface marker analysis using erythrocyte-forming rosetting, and OKT-3 and OKT-11 monoclonal antibodies on paired samples of treated and untreated marrow demonstrated a mean depletion to 1% of the original number of T-cells. Proliferative responses to alloantigens and mitogens as well as cytotoxic and natural killer cell function were tested and found to be markedly reduced. Despite these effects on T-lymphocytes, viable hematopoietic stem cell colonies were retained. Clinical results following the in vitro T-lymphocyte depletion of donor bone marrow for the 8 histocompatible and 15 nonhistocompatible bone marrow transplantation are reported. Prompt engraftment with minimal GVHD, despite no posttransplant GVHD prophylaxis, was seen in seven of the matched patients. In the nonhistocompatible bone marrow transplantation, failure of engraftment occurred in 11 patients. Grades III-IV GVHD were seen in two of the four patients that engrafted despite good T-lymphocyte depletion. No predictive correlation could be found between the in vitro analysis of marrow following CT-2 treatment and clinical outcome.
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PMID:In vitro analysis of donor bone marrow following monoclonal antibody treatment for the prevention of acute graft versus host disease. 353 Apr 39

We studied the presence of peripheral-blood- and bone-marrow-derived T-lymphocyte colony formation (CFU-TL) in 28 bone marrow transplant recipients from 1 month to six years after transplantation. Peripheral blood leukocyte and lymphocyte counts were generally normal, and all had morphologic evidence of engraftment without leukemia at the time of study. Both peripheral-blood- and bone-marrow-derived CFU-TL were markedly reduced after transplantation as compared to normal controls, which included bone marrow donors (14.2 +/- 5/4 X 10(4) vs 313 +/- 100/4 X 10(4) [p less than 0.001] and 26 +/- 4/2 X 10(5) vs 1004 +/- 60/2 X 10(5) [p less than 0.001]). Among the patients, four had no detectable bone-marrow-derived CFU-TL when tested less than six months after transplantation. Peripheral blood CFU-TL, while present in all patients, was markedly decreased for more than 12 months after transplantation. After two years, the number of CFU-TL returned to normal in several patients. The abnormalities in CFU-TL were unrelated to diagnosis, age, sex, graft-versus-host disease (GVHD), pretransplant conditioning, or posttransplant immunosuppressive treatment. Patients receiving autologous bone marrow transplants also had decreased CFU-TL. Cocultures of normal peripheral-blood- or bone-marrow-derived mononuclear cells with recipients' mononuclear cells or sera did not inhibit normal CFU-TL growth. Furthermore, the addition of mononuclear cells or sera from normal individuals, or of exogenous interleukin 1 or interleukin 2, did not correct the deficiency of CFU-TL growth by recipient cells. Depletion of T-lymphocytes from bone marrow or peripheral blood in transplant recipients by physical techniques or with a monoclonal antibody (CT-2) and complement had no effect on CFU-TL recovery. Similarly, addition of recipients' T cells to normal peripheral blood or bone marrow mononuclear cells did not suppress CFU-TL. These data indicate that most transplant recipients have a marked reduction in CFU-TL which persists for up to two years after transplantation. This reduction in the growth of T-cell colonies appears to be due to deficient numbers of these cells or an intrinsic defect in their responsiveness to T-cell lymphokines, rather than a result of growth suppression by inhibitory cells or serum factors. This observed defect in CFU-TL may have implications for therapeutic attempts to facilitate immune reconstitution after bone marrow transplantation.
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PMID:Abnormal T-lymphocyte colonies (CFU-TL) following bone marrow transplantation. 353 45

CT-2 mouse monoclonal antibody to the E-rosette receptor was used with complement to deplete bone marrow of E-rosette-positive cells (T cells). Depletion of E-rosette-positive cells was complete and nontoxic to hematopoietic progenitor cells. Depletion of E-rosette-positive cells with CT-2 may decrease the severity of graft-versus-host disease following bone marrow transplantation and extend the application of bone marrow transplantation to those without HLA-identical donors.
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PMID:Depletion of T cells from human bone marrow with monoclonal antibody CT-2 and complement. 638 32