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)

The European Bone Marrow Transplant Leukaemia Registry has collected data from 52 European centers between 1979 and 1986. More than 2,000 transplants performed for a haematological malignancy were reported. The present analysis shows that the most important factor influencing leukaemia free survival, transplant related mortality and relapse incidence is the stage of the disease at the time of the transplant. Outcome is highly better when the transplant is performed for acute myeloid and acute lymphocytic leukaemia in first complete remission and for chronic myelocytic leukaemia in first chronic phase. Additional prognostic factors are age, the method for graft-versus-host disease prevention and the donor recipient sex combination. Results are better for younger patients, for patients given cyclosporine for prevention of graft-versus-host disease and are worse for male patients receiving a female donor bone marrow. The results are not influenced by the year of the transplant per se and by the center size.
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PMID:Bone marrow transplantation for leukaemia in Europe. 248 Feb 74

Bone marrow transplantation (BMT) offers potentially curable treatment for patients with high-risk hematologic malignancies. However, relapse remains the major cause for failure of autologous BMT in these diseases and of allogeneic BMT in subsets of patients with these diseases. With our current preparative regimens, relapse rates following autologous BMT are over 30% for patients with intermediate or high-grade non-Hodgkin lymphoma and relapsed Hodgkin's disease in sensitive relapse and over 50% following autologous BMT for patients with acute non-lymphoblastic leukemia (ANLL) and acute lymphoblastic leukemia (ALL). Relapse rates exceed 80% in patients treated with autologous BMT for non-Hodgkin lymphomas and Hodgkin's disease in drug-resistant relapse. We also see a relapse rate over 50% in patients given allogeneic BMT for ANLL in second or third remission or early relapse, for ALL in third or subsequent remission or early relapse, and for chronic myelogenous leukemia (CML) in accelerated phase or blast crisis. We have explored two new approaches for improving the anti-tumor activity of our BMT preparative regimens. One involves combining etoposide, a chemotherapeutic agent that has excellent activity against leukemias and lymphomas, has shown synergistic activity with cyclophosphamide in vitro, and can be substantially dose-escalated, with busulfan and cyclophosphamide. The other approach attempts to induce graft-versus-host disease (GVHD), which appears to provide a clinical anti-tumor effect following allogeneic BMT, in recipients of autologous BMT. A syndrome similar to mild GVHD has been reported to occur spontaneously in a small number of patients receiving autologous or syngeneic transplants. GVHD can also be induced in rats undergoing syngeneic BMT by treatment with cyclosporine (CSA).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New conditioning regimens for high risk marrow transplants. 262 18

Fifteen adult patients undergoing allogeneic bone marrow transplantation (BMT) received cyclosporine (CSP) as prophylaxis of graft versus host disease (GVHD). In our patients eleven were hematologic malignancies, and four were severe aplastic anemia. Twelve patients were HLA-matched, and three were one locus mismatched. Three patients received CSP only, twelve received CSP and short term methotrexate. Seven patients had acute GVHD, but GVHD over Grade II were seen in only 3 patients who were transplanted from HLA-one locus mismatched donor. 7 patients had chronic GVHD. CSP were given intravenously at 3-5 mg/kg, starting 1 day before BMT. From about day 30, CSP was given orally. CSP concentrations when patients were given orally were lower in patients who had chronic GVHD. Although hypertension and water retention were seen in 8 patients, and renal dysfunction was seen in 3 patients, the side effects of CSP were mild and transient. There were no correlations between serum concentrations and the side effects of CSP. Three patients had the disturbance of hematopoiesis. Ten of fifteen patients are alive at median follow-up of 18.5 months (8-41 months) after BMT.
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PMID:[Cyclosporine as prophylaxis for graft versus host disease in adults undergoing allogeneic bone marrow transplantation]. 267 37

Allogeneic bone marrow transplantation can cure a substantial proportion of patients with hematologic malignancies. However, graft versus host disease (GvHD) and a sometimes long lasting immunodeficiency are the major obstacles to an improved survival rate. Passive immunization is a prophylactic and therapeutic approach increasingly considered in these patients and the question as to whether or not this expensive treatment is efficacious needs thorough evaluation. Several studies have been completed using either polyvalent immunoglobulins or CMV-hyperimmunoglobulin to prevent fatal CMV pneumonia posttransplant. Most studies did show a decreased mortality from this complication when immunoglobulins were given at higher doses in weekly intervals. Studies are also underway to evaluate, if the incidence of GvHD can be decreased by immunoglobulins, since it is known that infections can trigger the clinical manifestation of this complication. It is too early to say if bacterial and fungal infections after engraftment can be diminished specifically in patients at risk for infectious complication such as those with chronic GvHD. A hyperimmunoglobulin against varicella zoster is recommended in case a transplant patient has been exposed to varicella. It can also be given as an additive measure in severe disseminated varicella infections. Hyperimmunoglobulins against pseudomonas aeruginosa are currently being studied in humans and it is too early to decide whether or not they have a positive impact on patient survival.
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PMID:[Is the administration of immunoglobulins following bone marrow transplantation indicated?]. 282 97

The 1988 UCLA symposium on bone marrow transplantation (BMT) provided a comprehensive overview of the current position of this therapy in its widest sense. Major consideration was given to the role of BMT in the treatment of the acute and chronic leukaemias, with particular reference to the timing of this procedure in these disorders. The use of autologous grafting in haematological and non-haematological malignancy was discussed, and the results of BMT in aplastic anaemia and the inherited immune and metabolic diseases were presented. The prevention and therapy of the major post-transplant complications, cytomegalovirus interstitial pneumonitis and graft-versus-host disease, were the subject of lengthy deliberations as were the related topics of T cell depletion, graft-versus-leukaemia and the use of partially matched related or matched unrelated donors.
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PMID:Bone marrow transplantation: current controversies. 284 44

Twelve patients with haematological malignancy received cyclophosphamide 120 mg/kg, fractionated total body irradiation 12 Gy, oral cyclosporin and an HLA-identical sibling marrow transplant depleted of T cells by incubation with monoclonal antibodies directed against the CD2 and CD8 antigens and rabbit complement. The phenotype of the residual T cells in the donor marrow inocula was CD3+, CD4+, CD8-. To exclude the possibility that this represented modulation or blocking of the CD8 antigen, T-depleted and non-depleted marrow aliquots from these donors were bulk-cultured for 10 days with phytohaemagglutinin and interleukin-2. Even after this attempted expansion, only a small proportion of cultured T cells from the depleted aliquots (in contrast to the non-depleted aliquots) expressed the CD8 antigen. Since all patients receiving CD3+, CD4+, CD8- marrow developed mild or moderate acute graft-versus-host disease (GVHD), we conclude that CD4+ T cells are capable of initiating acute GVHD across non-MHC barriers in man.
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PMID:CD4+ T cells appear capable of initiating graft-versus-host disease across non-major histocompatibility complex (MHC) barriers in man. 290 76

Risk factors for acute graft-versus-host disease (GvHD) remain controversial. We performed uni- and multivariate statistical analyses on a series of 37 patients receiving a non-depleted allogeneic bone marrow transplant from an HLA-identical sibling donor for a haematological malignancy, in order to identify risk factors for GvHD. Three factors were associated with development of moderate to severe GvHD: a positive mixed epidermal cell-lymphocyte reaction (MECLR) between donor and recipient, previous pregnancies in female donors and chronic myeloid leukaemia diagnosis. The MECLR was the most important predictive factor, selected in first rank by the stepwise linear discriminant analysis. Combining these three prognostic factors in the jackknifed procedure, we could correctly classify 33/37 patients in two groups: grade O-I versus grade II-IV acute GvHD. These results should apply to donor selection and to predict donor/recipient pairs at high risk of GvHD who might benefit of bone marrow T-cell depletion and those at low risk for whom depletion could be avoided.
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PMID:The mixed epidermal cell lymphocyte-reaction is the most predictive factor of acute graft-versus-host disease in bone marrow graft recipients. 297

The results of a prospective randomised trial comparing cyclosporin (CSP) with methotrexate (MTX) as immunosuppressive therapy after HLA-identical sibling marrow transplantation for patients with acute leukemia in first remission were analysed 2.5 years after entry of the last patient into the trial. Patients given cyclosporin showed a faster rate of marrow engraftment, less oro-pharyngeal mucositis, more azotemia and more diastolic hypertension than those receiving methotrexate. Actuarial four-year survival was 69% for patients receiving MTX and 43% for those receiving cyclosporin (not significant). Actuarial four-year survival in continuous complete remission from the time of transplant was 69% and 38% respectively (not significant, p = 0.09). While there was no difference in the incidence or severity of acute or chronic graft-versus-host disease, the actuarial rate of leukemic recurrence was 0% in the MTX and 36% in the GSP group (p = 0.02). This finding emphasises the importance of long-term follow up for the full assessment of new therapeutic protocols of marrow transplantation in the treatment of hematological malignancy.
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PMID:A prospective randomised trial of cyclosporin versus methotrexate after HLA-identical sibling marrow transplantation for patients with acute leukemia in first remission: analysis 2.5 years after last patient entry. 305 5

In vitro depletion of mature pan-T lymphocytes has been widely and successfully used to prevent acute graft-versus-host disease (GVHD) after allogeneic bone-marrow transplantation (BMT). However, this procedure has been associated with a high incidence of graft failure and leukemic relapse. In this pilot study, we evaluated the efficiency of a selective depletion of human marrow T cytotoxic lymphocytes (CD8), a subset essential to induce GVHD in mice. Eleven patients with hematologic malignancies were included (7 HLA-matched BMT, 4 HLA-mismatched BMT). Marrow treatment with 7 anti-CD8 mAbs and rabbit complement resulted in a marked reduction of CD8+ lymphocytes from 15% (median value; range 7%-31%) to 1% (median value; range less than 1%-11%). Acute GVHD was not abolished by this procedure despite postgraft immunosuppression. One patient (HLA-mismatched BMT) rejected his graft and had a full autologous recovery. In conclusion, when compared to the data in the literature, CD8 depletion was shown to be less efficient than pan-T-cell depletion in the prevention of GVHD after allogeneic BMT and was still associated with a major complication associated with this procedure, i.e., graft failure.
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PMID:Selective depletion of marrow-T cytotoxic lymphocytes (CD8) in the prevention of graft-versus-host disease after allogeneic bone-marrow transplantation. 307 87

122 patients with hematologic malignancies underwent allogeneic marrow transplantation from HLA-matched sibling donors and received one of two forms of infection prophylaxis while granulocytopenic: 1) decontamination and laminar air flow isolation (LAF, 68 patients), and 2) LAF plus prophylactic systemic antibiotics (LAF + PSA, 54 patients). Patients were evaluated for infection acquisition while in isolation. Septicemia occurred in 11 (16%) of the patients in the LAF group and in three (6%) patients in the LAF + PSA group. Fourteen (21%) of the patients in the LAF group and four (7%) patients in the LAF + PSA group had a major local infection. There was no difference in the incidence and severity of graft-versus-host disease or incidence and duration of fever. The addition of prophylactic intravenous broad-spectrum antibiotics for patients isolated in LAF rooms significantly decreased infection acquisition.
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PMID:Laminar air flow isolation and decontamination: a prospective randomized study of the effects of prophylactic systemic antibiotics in bone marrow transplant patients. 308 39


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