Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment with the monoclonal antibody OKT3 specific for the CD3 complex associated with the T cell antigen receptor can reverse acute rejection of human renal allografts. However, efficacy of anti-CD3 antibodies for treatment of patients with acute graft-versus-host disease after marrow transplantation has not been established. The dose-limiting side effects resulting from T cell activation induced by some anti-CD3 antibodies in vivo have discouraged their use for this application. We now report a phase I-II study of GVHD treatment with the anti-CD3 antibody BC3, a monoclonal murine IgG2b that, unlike OKT3, does not activate T cells. Fourteen patients were treated with BC3 after progression of acute GVHD despite treatment with cyclosporine and corticosteroids, and three patients received BC3 as primary treatment for GVHD. BC3 was administered at a dose of 0.1 or 0.2 mg/kg/day for seven or eight days. Five patients achieved complete resolution of GVHD, eight patients had partial improvement, two patients had no change, and two patients had progression of GVHD on therapy. Responses were sustained in 8 of 13 patients. Mild chills, fever, hypertension, and chest discomfort occurred in various combinations following 6 of 17 (35%) initial infusions of BC3 and following 4 of 99 (4%) subsequent infusions. In each instance it was possible to continue BC3 therapy without adjusting the dose or treatment schedule. In each patient treated, the absolute count of peripheral blood lymphocytes decreased transiently but returned to baseline within 22 hr after the first infusion. Circulating T cells had surface CD3 molecules saturated by the infused antibody in all but one patient. Four patients survived longer than one year after treatment with antibody BC3, and 13 patients died of infection or organ failure. Administration of the nonmitogenic anti-CD3 antibody BC3 was associated with improvement in the clinical manifestations of GVHD with minimal acute toxicity. Efficacy of antibody treatment did not depend on depletion of circulating T cells. Therefore, antibody BC3 may be achieving therapeutic immunosuppression by modulating T cell function. Controlled studies in patients treated earlier in the course of GVHD should determine whether antibody BC3 can improve survival.
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PMID:Treatment of acute graft-versus-host disease with a nonmitogenic anti-CD3 monoclonal antibody. 144 Aug 52

In order to determine the incidence and causes of death during the first 100 days after BMT (early deaths) in a pediatric population we have examined data reported in the AIEOP BMT Registry. Up to July 1990, data on 486 children who underwent allogeneic (180) or autologous (306) BMT were evaluable. The children had acute lymphoblastic leukemia (148 cases), acute non-lymphoblastic leukemia (127 cases), neuroblastoma (82 cases), chronic myelogenous leukemia (15 cases), aplastic anemia (nine cases), solid tumors, lymphoma, immunodeficiency or storage diseases. The overall survival is 55% for allogeneic HLA matched and 38% for autologous transplants at 5 years, 24% for HLA mismatched graft at 2 years. Out of the 486 children, 70 (14%) died during the first 100 days after BMT: 33/306 (11%) after autologous BMT, 24/150 (16%) after allogeneic matched BMT and 13/30 (43%) after mismatched BMT. Causes of early death were as follows: disease progression: 12 children (10/306 after autologous and 2/180 after allogeneic BMT); infection: 12 children (five after autologous and seven after allogeneic BMT); interstitial pneumonitis: 21 children (seven after autologous and 14 after allogeneic BMT); cardiac failure: five children (four after autologous BMT); veno-occlusive disease: eight children (three after autologous, five after allogeneic BMT); acute renal failure: three children (one after autologous and two after allogeneic BMT); multiple organ failure: two cases (one after autologous BMT); cerebral hemorrhage: three children (one after autologous BMT); hypertension: one child; acute GVHD: three children (12% of early deaths after allogeneic BMT).
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PMID:Early deaths in children after BMT. Bone Marrow Transplantation Group of the Italian Association for Pediatric Hematology and Oncology (AIEOP) and Gruppo Italiano Trapianto di Midollo Osseo (GITMO). 146 3

Regimens using cyclosporin (CSP) and either methylprednisolone (MP) or methotrexate (MTX) have been useful in the prophylaxis of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). However, CSP produces a number of side effects, including neurologic toxicity. A retrospective review of recipients of 239 BMTs given CSP-based prophylactic regimens revealed that 10 patients (4.2%, 95% confidence interval 0% to 10.4%) experienced a syndrome characterized by hypertension, severe visual disturbances, seizures and occipital lobe density changes on brain computed tomography (nine patients) or nuclear magnetic resonance imaging (one patient). Neurologic findings were reversible in all cases, usually after temporary discontinuation of CSP. Univariate analysis identified the following risk factors for neurotoxicity: use of unrelated or HLA-mismatched related donors, administration of etoposide (VP-16) or total body irradiation as part of conditioning, use of corticosteroids for prophylaxis or treatment of acute GVHD, or development of either acute GVHD or clinically significant microangiopathic hemolytic anemia (MAHA) post-BMT. In multivariate analysis, the most important predictors were the use of VP-16 (p = 0.008), the use of a continuous infusion CSP plus MP prophylactic regimen for GVHD (p = 0.003) and the development of MAHA after BMT (p less than 0.001). The strong association with MAHA suggests that endothelial damage is related to the development of this complication.
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PMID:Neurologic complications in allogeneic bone marrow transplant patients receiving cyclosporin. 176 75

The involvement of an auto-immune mechanism has been suggested in the development and/or the maintenance of hypertension in male, genetically hypertensive rats of the Lyon strain (LH). The aim of this study was to determine whether hypertension may be transferred, by lymphoid cells, from hypertensive donors to male, normotensive rats of the Lyon strain (LN). Experiments designed to induce a resistance to hypertension in LH rats by transfer of lymphoid cells from LN animals were also performed. Since LH and LN are mismatched at the major histocompatibility complex, transfers of fetal liver cells (FLC) from fetuses of 13-14 days gestation were performed. These experiments demonstrate the ability of FLC to allow a prolonged survival (over 17 weeks) without graft versus host disease in the rat. As regards the blood pressure level, no LN recipient having received FLC from LH donor became hypertensive, thus showing that hypertension cannot be transferred by lymphoid cells in normotensive animals. Resistance to hypertension was so weakly transferred to hypertensive rats (results being significantly different only at 10 weeks post-grafting) that it may be considered doubtful.
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PMID:Fetal liver cell transplantation fails to transfer hypertension from genetically hypertensive rats to normotensive rats of the Lyon strain. 184 65

Five of 182 recipients of allogeneic bone marrow transplants performed between 2/84 and 6/90 developed seizures while receiving cyclosporine and methylprednisolone to prevent acute graft-versus-host disease. All received a radiation-free regimen of busulfan and cyclophosphamide as preparative therapy. Two patients received HLA-mismatched allografts; and three patients received marrow from HLA-identical sibling donors. Two patients had received extensive intrathecal therapy prior to transplantation. All patients were receiving standard prophylactic doses of CsA and MP at the time of onset (median 31 days posttransplantation) of seizures. Three patients had mild-to-moderate hypertension and varying degrees of morphologic evidence of microangiopathic hemolytic anemia. None had unusually low magnesium levels. Cyclosporine levels were not in the toxic range. Cranial magnetic resonance imaging and computed tomography (CT) showed bilateral abnormalities primarily in the posterior temporal, occipital, and parietal lobes. These abnormalities were shown to be transient on sequential MRI exams in two patients. Seizures as well as radiologic abnormalities resolved on stopping CsA and did not recur in 2 patients who subsequently received CsA in lower doses. These findings confirm and expand previous observations of CsA-associated seizures and demonstrate that they occur in allogeneic bone marrow transplant recipients following a radiation-free preparative regimen of busulfan and cyclophosphamide.
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PMID:Cyclosporine-associated seizures in bone marrow transplant recipients given busulfan and cyclophosphamide preparative therapy. 187 5

One hundred and sixty eight adult patients with B-cell non-Hodgkin's lymphoma (NHL) and other hematologic malignancies who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic-uremic syndrome (HUS). All patients were conditioned with cyclophosphamide and total body irradiation. When examined at 3-month intervals for the first year post-BMT, all patients had uniform measurements of hematocrit (Hct) and serum creatinine. Sixteen patients who initially exhibited Hct and creatinine values that were normal range for the BMT populations developed a sudden decrease in Hct and increase in creatinine between 3 and 11 months post-BMT and fulfilled the clinical and laboratory criteria for HUS. None of these patients had known active cytomegalovirus infection, graft-versus-host disease, or cyclosporine administration. The degree of decrease in Hct and creatinine elevation ranged from solely laboratory abnormalities to a clinically significant syndrome. Twelve of the 16 patients developed acute clinical complications of congestive heart failure, hypertension (HTN), or peripheral edema. Twelve patients required red blood cell support, whereas only four patients required platelet transfusions. Both hemolytic anemia and thrombocytopenia have resolved in virtually all cases. At a mean follow up of 18 months postdiagnosis, creatinine elevations have persisted along with HTN. All patients have survived without life-threatening long-term sequelae. With the increasing use of BMT as a curative modality for patients with hematologic malignancies, it becomes important to prospectively monitor patients for the development of HUS and its potential long-term impact on renal function.
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PMID:Hemolytic-uremic syndrome following bone marrow transplantation in adults for hematologic malignancies. 201 7

A murine IgG1 antibody specific for the IL-2-binding site on the human lymphocyte IL-2 receptor beta chain (CD25) was evaluated in 11 patients who developed acute graft-versus-host disease following allogeneic marrow transplantation. All patients had received cyclosporine and methotrexate for prophylaxis of GVHD, either alone (4 cases), or in combination with antithymocyte globulin (4 cases) or with prednisone (3 cases). Patients had developed GVHD at 7-53 days (median 12) after transplantation and had failed treatment with corticosteroids for 3-44 days (median 19). Residual GVHD was of grade II severity in 4 patients, grade III in 5 patients, and grade IV in 2 patients. Sequential patients received monoclonal antibody in escalating doses from 0.1 mg/kg/day to 1.0 mg/kg/day for 7 days. Side effects were fever, respiratory distress, hypertension, hypotension, and chills occurring in 11 of 72 (14%) antibody infusions. Trough antibody levels greater than 6 micrograms/ml were achieved in patients treated with 0.5 or 1.0 mg/kg/day. Four of eight evaluable patients had an IgM antibody response, and one had an IgG response to the murine immunoglobulin. Clinical response of GVHD was evaluated in 10 patients who received the entire course of the antibody treatment. Among 7 patients treated within 40 days from transplantation, one patient had a complete response in the skin as the only involved organ, and 3 patients had a partial response, 2 in the skin and one in the gastrointestinal tract. No responses were achieved with liver disease at anytime or in any organ in patients treated beyond 40 days after transplantation. Since administration of this antibody was well tolerated and some efficacy was observed in patients with acute GVHD treated early after transplantation, there is a rationale for testing this antibody as an agent for prophylaxis of GVHD.
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PMID:A phase I-II study evaluating the murine anti-IL-2 receptor antibody 2A3 for treatment of acute graft-versus-host disease. 236 50

The feasibility and toxicity of six-week continuous intravenous 3 mg/kg/day cyclosporine (CsA) treatment in conjunction with a short course of methotrexate (MTX) was studied in 69 consecutive patients after HLA genotypically identical bone marrow transplantation. In light of the uncertain efficacy of prolonged oral CsA immunoprophylaxis in preventing de novo chronic graft-versus-host disease (GVHD). CsA treatment was terminated three months after BMT. Sixty-one (88%) patients received the full intravenous regimen and no patient exclusions were necessary due to intolerable adverse effects. Weekly median blood CsA concentrations ranged between 820 ng/ml in the first and 648 ng/ml in the sixth week of treatment. No significant correlation existed between blood CsA concentrations and CsA dosages. Major adverse effects of the regimen included hypertension in 36%, acute nephrotoxicity in 36%, acute hepatotoxicity in 41%, and central nervous system toxicity in 4% of the patients. Since hepatotoxicity occurred predominantly in the early posttransplant period (median onset day 9), the relatively high incidence of this untoward effect might have been additionally caused by MTX and/or the preparative regimen. Blood CsA concentrations and CsA dosages did not significantly correlate with serum creatinine or total and conjugated bilirubin levels. In addition, blood CsA and serum creatinine levels did not differ between hypertensive and normotensive patients. Acute GVHD developed in 16% of the patients. Median CsA doses and blood CsA concentrations were identical for each week after BMT for patients contracting acute GVHD as compared with those without acute GVHD. In 55 patients surviving without acute or secondary chronic GVHD, the cumulative probability of de novo chronic GVHD after termination of CsA treatment was 13%. In conclusion, this regimen was tolerable and provided constant blood CsA concentrations for six posttransplant weeks that were not adversely influenced by the development of acute GVHD. Restriction of CsA treatment to the first three months after BMT appeared not to increase the risk of de novo chronic GVHD, which challenges regimens employing oral CsA immunoprophylaxis for 6-12 months after BMT.
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PMID:Six weeks of continuous intravenous cyclosporine and short-course methotrexate as prophylaxis for acute graft-versus-host disease after allogeneic bone marrow transplantation. 240 91

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

Between 1982 and 1986 51 patients were treated with ciclosporin a (CSA) to prevent graft versus host disease (GvHD) after bone marrow transplantation (BMT). Major side effects of the drug were tremor, hypertension, hepatotoxicity and nephrotoxicity. Acute GvHD 0 degree to II degree occurred in 80% of our patients, and GvHD III degree and IV degree in 20% despite the use of CSA. Two to four days before the onset of GvHD, CSA serum levels were significantly lower on the average in patients who developed GvHD III degree and IV degree compared to the others. Our data indicate that plasma CSA concentrations higher than 250 ng/ml should be achieved to reduce the severity of GvHD after BMT.
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PMID:Correlation between low CSA plasma concentration and severity of acute GvHD in bone marrow transplantation. 304 89


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