Cyclosporine, Methotrexate, and Prednisone Compared with Cyclosporine and Prednisone for Prophylaxis of Acute Graft-versus-Host Disease

Chao, NJ; Gm, Schmidt; Jc, Niland; Amylon,; Ac, Dagis; Long, GD; Nademanee, AP; Negrin, RS; Mr, O'Donnell; Parker, Pablo

doi:10.1056/nejm199310213291703

Cited by 254 publications

(120 citation statements)

References 23 publications

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“…Clinical observations with allotransplanted patients support these findings. For example, a combination of MTX, CsA and prednisone was found to be more effective in preventing acute GVHD than the combination of CsA and prednisone alone [50][51][52], supporting the idea that MTX deletes activated T cells that have escaped from proliferation blockade by other ISD. Recent data from mice with lupus nephritis also indicate that a treatment, which combines the inhibition of T cell activation by CTLA4Ig and the induction of apoptosis in immune cells by CP, reduced renal disease and prolongs survival [53].…”

Section: Discussionmentioning

confidence: 88%

Induction of apoptosis and modulation of activation and effector function in T cells by immunosuppressive drugs

Strauß

Osen

Debatin

2002

Clinical and Experimental Immunology

151

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SUMMARYImmunosuppressive drugs (ISD) are used for the prevention and treatment of graft rejection, graftversus-host-disease (GVHD) and autoimmune disorders. The precise mechanisms by which ISD interfere with T cell activation and effector function or delete antigen-specific T cells are defined only partially. We analysed commonly used ISD such as dexamethasone (DEX), mycophenolic acid (MPA), FK506, cyclosporin A (CsA), rapamycin (RAP), methotrexate (MTX) and cyclophosphamide (CP) for apoptosis-induction and modulation of activation and effector function in human peripheral T cells, cytotoxic T cell lines (CTL) and Jurkat T cells. Of all drugs tested only CP and MTX prevented antigenspecific proliferation of T cells and decreased cytotoxicity of alloantigen specific CTL lines by direct induction of apoptosis. MTX and CP also slightly increased activation-induced cell death (AICD) and CD95-sensitivity. In contrast, all other drugs tested did not induce T cell apoptosis, increase CD95-sensitivity or AICD. CsA and FK506 even prevented AICD by down-modulation of CD95L. DEX, MPA, CsA, FK506 and RAP inhibited activation of naive T cells, but were not able to block proliferation of activated T cells nor decrease cytotoxic capacity of CTL lines. These results show that ISD can be classified according to their action on apoptosis-induction and inhibition of proliferation and would favour a rational combination therapy to delete existing reactive T cells and prevent further T cell activation.

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Section: Discussionmentioning

confidence: 88%

Induction of apoptosis and modulation of activation and effector function in T cells by immunosuppressive drugs

Strauß

Osen

Debatin

2002

Clinical and Experimental Immunology

151

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“…Likewise, mycophenolate mofetil added to initial treatment for chronic GVHD appeared to increase the risk of relapse. 22 On the other hand, the risk of relapse was not increased by methotrexate added to cyclosporine and prednisone for prevention of GVHD, 23 by prophylaxis or treatment with glucocorticoids 24,25 or by azathioprine added to initial treatment for chronic GVHD. 26 The current retrospective study was intended to provide a broad overview of associations of acute GVHD, NIH chronic GVHD, and IST with risks of recurrent malignancy and mortality after allogeneic HCT.…”

Section: Introductionmentioning

confidence: 99%

Influence of immunosuppressive treatment on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation

Inamoto

Flowers

Lee

et al. 2011

Blood

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This study was conducted to elucidate the influence of immunosuppressive treatment (IST) and GVHD on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation (HCT). The study cohort included 2656 patients who received allogeneic HCT after highintensity conditioning regimens for treatment of hematologic malignancies. Rates and hazard ratios of relapse and mortality were analyzed according to GVHD and IST as time-varying covariates. Adjusted Cox analyses showed that acute and chronic GVHD were both associated with statistically similar reductions in risk of relapse beyond 18 months after HCT but not during the first 18 months. In patients with GVHD, resolution of GVHD followed by withdrawal of IST was not associated with a subsequent increase in risk of relapse. In patients without GVHD, withdrawal of IST was associated with a reduced risk of relapse during the first 18 months, but the risk of subsequent relapse remained considerably higher than in patients with GVHD. In summary, the association of GVHD with risk of relapse changes over time after HCT. In patients without GVHD, early withdrawal of IST might help to prevent relapse during the first 18 months, but other interventions would be needed to prevent relapse at later time points. (Blood. 2011;118(2): 456-463)

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“…Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporin A (CsA), methotrexate, and methylprednisolone according to Chao et al's method. 7 CsA was infused from day Ϫ1 for 24 h, and was kept at a target blood level of 400 to 600 ng/ml until marrow engraftment, after which the dosage was varied depending on the symptoms of GVHD. G-CSF was administered at a dose of 8 g/kg from day 5 to day 19.…”

Section: Casementioning

confidence: 99%

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome following allogeneic bone marrow transplantation

Takatsuka

Wakae

Mori

et al. 2002

Bone Marrow Transplant

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Summary:We monitored the levels of various cytokines and chemokines, as well as an adhesion molecule and factors related to vascular endothelial damage, in three patients with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome after bone marrow transplantation. Measurements were done at the onset of this condition and during plasma exchange for treatment. At the onset of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, the levels of interleukin-8, thrombomodulin, and plasminogen activator inhibitor-1 were all markedly increased. A close relationship was observed between improvement in symptoms by plasma exchange and a decrease in interleukin-8 level, suggesting that this chemokine may be related to the development of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome after bone marrow transplantation. Bone Marrow Transplantation (2002) 29, 907-911.

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Cyclosporine, Methotrexate, and Prednisone Compared with Cyclosporine and Prednisone for Prophylaxis of Acute Graft-versus-Host Disease

Abstract: The combination of cyclosporine, methotrexate, and prednisone was more effective in preventing acute GVHD of grades II to IV than was the combination of cyclosporine and prednisone without methotrexate.

Cited by 254 publications

References 23 publications

Induction of apoptosis and modulation of activation and effector function in T cells by immunosuppressive drugs

Induction of apoptosis and modulation of activation and effector function in T cells by immunosuppressive drugs

Influence of immunosuppressive treatment on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome following allogeneic bone marrow transplantation

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