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 report details of renal involvement during the course of chronic graft-versus-host disease (cGVHD) in two patients undergoing bone marrow transplantation as treatment for acute leukemia. In both cases, the clinical picture was primarily characterized by proteinuria without hypertension or renal failure. Electron microscopy of renal biopsy specimens revealed a similar pattern in the two cases with extensive coalescence of foot processes and intramembraneous deposition of electron-dense material. Our data suggest that the kidney may be a target organ in chronic GVHD.
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PMID:Renal involvement in chronic graft-versus-host disease: a report of two cases. 304 98

Patients with haematological malignancies with HLA-identical marrow donors were randomized to treatment with cyclosporin (CSA) or methotrexate (MTX). Two of the 29 patients randomized to MTX died before engraftment compared with none of the 30 treated with CSA. Engraftment by leucocytes (P less than 0.0001), granulocytes (P less than 0.02), and reticulocytes (P less than 0.01) was faster among the CSA patients. There were no significant differences between the two groups regarding transfusions, hospitalization and incidence of early septicaemia. Granulocyte transfusions were required in seven of 29 MTX and two of 30 CSA patients (not significant: NS). Overall (grade I-IV) acute graft-versus-host disease (GVHD) was more common (P = 0.001) in the CSA patients. Grade II-IV acute GVHD was seen in 40% of the CSA patients compared with 22% in the MTX patients (NS). In the adult patients grade II-IV GVHD was slightly more common (P less than 0.05) in those treated with CSA compared with MTX. Chronic GVHD appeared in 30 and 39% in the two groups respectively. Actuarial 3-year survival was 58% for the CSA patients and 69% for the MTX patients. There were no significant differences regarding the incidence of interstitial pneumonitis or relapses between the two groups. The side-effects of CSA treatment includes nephrotoxicity (83%), hepatotoxicity (20%), hirsutism (43%), hypertension (23%), tremor (27%) and gingival hyperplasia (27%). Serum creatinine values were increased at 3 and 6 months in the CSA group but were within the normal range after 6 months. A blind study on oral side-effects revealed that CSA patients more often had a normal mucosa (P = 0.025) and less frequently had mucositis (P = 0.01) compared with the MTX group.
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PMID:A randomized trial comparing use of cyclosporin and methotrexate for graft-versus-host disease prophylaxis in bone marrow transplant recipients with haematological malignancies. 333 19

The efficacy and toxicity of cyclosporine (CsA) treatment for graft-versus-host disease (GVHD) was studied in 53 bone marrow transplant recipients. No correlation was found between acute or chronic GVHD and CsA dosage (daily or cumulative) or CsA plasma levels. Acute nephrotoxicity developed in 63% of the patients. Patients with nephrotoxicity had significantly higher CsA plasma levels during the first month after transplantation compared with patients without nephrotoxicity (P less than 0.05) although the cumulative CsA doses did not differ. Children had significantly fewer episodes of nephrotoxicity compared with adults (P less than 0.01). In spite of this, children received a significantly higher cumulative CsA dose (P less than 0.001). However, CsA plasma levels did not differ between children and adults, suggesting a difference in availability or elimination of the drug. Hypertension developed in 28% of the patients. Hypertensive patients tended to be younger compared with normotensive patients (P = 0.07). Nephrotoxicity tended to be less common in patients with hypertension (P = 0.06). No correlation existed between hypertension and CsA dose or CsA plasma levels. In conclusion, no correlation was found between CsA dose and GVHD or CsA toxicity, and in the single patient CsA plasma levels were of no value in predicting side effects of CsA treatment.
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PMID:The role of cyclosporine dosage and plasma levels in efficacy and toxicity in bone marrow transplant recipients. 355 61

We investigated the frequency of hypertension (sustained diastolic blood pressure greater than or equal to 90 mmHg) in 112 patients given HLA-identical marrow grafts. Patients were conditioned with 2 X 60 mg/kg of cyclophosphamide and 6 X 2 Gy of total body irradiation and randomized to receive as graft-versus-host disease prophylaxis either the standard methotrexate regimen (n = 61) or cyclosporine (n = 51), starting on day -1 as 12.5 mg/kg/d orally or as 3 mg/kg/d i.v. and later converting to p.o. when oral intake was tolerated. Kaplan-Meier estimates indicate a 60% incidence of hypertension in the first 120 d in patients given cyclosporine (median time to onset: 4 d post transplant) compared to 20% in patients given methotrexate (P less than 0.0001). Multifactorial analysis using a Cox regression model showed that cyclosporine was was the most significant risk factor for developing hypertension (relative risk: 32.1, P less than 0.0001). In addition, glucocorticoids, used for treatment of GVHD, were associated with an increased risk for hypertension (relative risk 7.2, P less than 0.0001). Age, sex, underlying disease, cyclosporine trough levels, and renal function had no significant association with hypertension. Early therapy of hypertension in cyclosporine-treated patients appears to be indicated.
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PMID:Incidence of hypertension after marrow transplantation among 112 patients randomized to either cyclosporine or methotrexate as graft-versus-host disease prophylaxis. 388 41

Fifty-six patients, 30-47 yr of age, with leukemia in relapse received allogeneic marrow transplants from HLA-identical siblings. All patients were treated with cyclophosphamide (120 mg/kg) and 7 daily fractions of 2.25 Gy of total body irradiation (TBI) for seven consecutive days. Nine patients (16%) are currently alive and free of disease 324-845 days from transplantation. The actuarial relapse and survival rates at 2 yr were 56% and 9.5% respectively. These data were not remarkably different from those in previous studies using 10 Gy of TBI administered as a single dose. Thirty patients were randomized to receive methotrexate (MTX) and 26 to receive cyclosporine (CSP) as postgrafting prophylaxis for acute graft-versus-host disease (GVHD). The probability of developing significant acute GVHD by day 100 post-transplant was 71% for patients in the MTX group and 45% for patients in the CSP group (p less than 0.05). The probability of relapse was 37% for patients in the MTX group and 70% for patients in the CSP group (p less than 0.05). Transplant-related deaths were more frequent in the MTX group and leukemic deaths were more frequent in the CSP group although this may have been related to an uneven distribution of high-risk patients. Long-term disease-free survival was comparable. Patients in the MTX group had more severe mucositis, more alveolar pneumonias and possibly more deaths due to complications of acute and chronic GVHD. Patients in the CSP group had a higher incidence of hypertension, neurological complications and renal dysfunction.
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PMID:Marrow transplantation for leukemia following fractionated total body irradiation. A comparative trial of methotrexate and cyclosporine. 390 82

Thirty-six patients received allogeneic (34) or syngeneic (two) bone marrow transplants as treatment for severe aplastic anaemia or acute leukaemia. Nineteen of the allogeneic recipients received methotrexate (MTX) and 15 received cyclosporin A (CyA) as the predominant immunosuppressive agent to minimize graft-versus-host disease (GVHD) post transplant. In the first 100 d post transplant renal dysfunction was much less frequent in the MTX recipients than in the CyA recipients who exhibited three distinct syndromes of nephrotoxicity: most commonly. CyA recipients developed asymptomatic azotaemia, proteinuria, urinary casts, impaired urinary concentrating ability and hypertension. Secondly, two CyA recipients developed acute reversible renal failure precipitated by systemic bacterial infection which required dialysis and in which the kidney was the sole target organ; thirdly, two recipients of HLA-genotypically non-identical grafts developed a rapidly progressive fatal syndrome with multiple organ involvement including lung, brain and kidney which clinically and histologically resembled thrombotic thrombocytopenic purpura.
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PMID:Cyclosporin A associated nephrotoxicity in the first 100 days after allogeneic bone marrow transplantation: three distinct syndromes. 634 55

Cyclosporin A(CyA) is a valuable post graft immunosuppressive agent in allogeneic bone marrow transplantation. The use of CyA is associated with a reduction in severity of graft versus host disease and improved marrow engraftment. A major side effect of CyA is nephrotoxicity. In 33 patients studied during the first 4 weeks of therapy there is a close correlation between trough (12 h) serum cyclosporin A concentrations and plasma creatinine (r = 0.93, P less than 0.001) and urea (r = 0.88, P less than 0.001). Trough CyA serum concentrations of greater than 500 ng/ml are potentially nephrotoxic. Other risk factors for early nephrotoxicity in cyclosporin therapy are the concurrent use of aminoglycoside antibiotics (P = 0.01) and hyperbilirubinaemia (P = 0.01). Early nephrotoxicity can be prevented by maintaining trough CyA levels in the range 100-400 ng/ml. During prolonged CyA therapy, cumulative renal impairment can occur and nephrotoxic episodes associated with microangiopathic peripheral blood changes and hypertension are seen in a minority of patients.
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PMID:Nephrotoxicity in bone marrow transplant recipients treated with cyclosporin A. 634 56

Oral cyclosporin A was used as prophylaxis against graft-versus-host disease in (a) 31 patients with acute leukaemia or aplastic anaemia given transplants of HLA-matched bone marrow and (b) five patients with inborn errors of metabolism given transplants of haplotype-identical (parental) bone marrow. Twenty-six patients survived longer than two months after the operation. Despite the cyclosporin A, 31 patients (86%) suffered an acute form of graft-versus-host disease and 22 (61%) a chronic form. Nevertheless, the disease was usually treatable with immunosuppressive agents and caused the death of only one patient. Cyclosporin A caused renal toxicity in all cases; occasionally this was associated with a "capillary leak" syndrome, fatal in two patients. In children hypertension, fits, and fluid retention were common side effects. Blood concentrations of cyclosporin A correlated with blood urea values and blood pressure but did not predict the occurrence of graft-versus-host disease. Four different dose schedules were used to find the optimum way to administer this drug. Oral cyclosporin A is extremely effective at reducing the severity of graft-versus-host disease, but prevention of the disease is limited by toxicity of the drug and variable absorption. Better results might be achieved with parenteral administration or by using the drug in combination with other methods.
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PMID:Cyclosporin A as prophylaxis against graft-versus-host disease in 36 patients. 680 91

A microangiopathic syndrome was observed in 3 of 14 (21%) patients receiving cyclosporine and methylprednisolone (CSA-MP) for graft-versus-host disease (GVHD) prophylaxis between January 1991 and June 1992 at our center. The syndrome consisted of neurological abnormalities, arterial hypertension, intravascular hemolysis with red cell fragmentation, and a drop in platelet counts after allogeneic bone marrow transplantation (BMT) for hematological malignancy, and it occurred around day 50 after BMT. Treatment with plasma exchanges against fresh-frozen plasma resulted in a decrease of serum lactate dehydrogenase and an improvement of neurological symptoms. We compared CSA-MP patients retrospectively with patients who had received cyclosporine and methotrexate (CSA-MTX) for GVHD prophylaxis (n = 70) at our institution. All patients in both groups engrafted. Day 100 survival (80% vs. 79%) and transplant-related mortality (16% vs. 14%) were identical in the two groups. CSA-MP patients had significantly more acute GVHD II-IV (57% vs. 17%, P < 0.01). Arterial hypertension (P < 0.01) and neurological symptoms (P < 0.01) were significantly more frequent in the CSA-MP group. The 11 asymptomatic CSA-MP patients had significantly higher lactate dehydrogenase levels (P < 0.01) and lower platelet counts (P < 0.01) at 40, 60, and 100 days after BMT, which suggests the presence of a subclinical form of microangiopathy. Significantly higher plasma levels of von Willebrand factor antigen in CSA-MP patients on day 50 after BMT (P < 0.05) and absence of large von Willebrand factor multimers on gel electrophoresis in 4 of 13 (31%) CSA-MP patients compared with 0 of 14 (0%) CSA-MTX patients (P < 0.01) further suggest profound endothelial damage in patients receiving CSA-MP for GVHD prophylaxis.
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PMID:Microangiopathy following allogeneic marrow transplantation. Association with cyclosporine and methylprednisolone for graft-versus-host disease prophylaxis. 749 99

The application of lung transplantation to the pediatric population was a natural extension of the success realized in our adult transplantation program, which began in 1982. Twenty pediatric patients (age range 3 to 18 years) have had heart-lung (n = 11), double lung (n = 8), and single lung (n = 1) transplantation procedures. The causes of end-stage lung disease were primary pulmonary hypertension (n = 7), congenital heart disease (n = 5), cystic fibrosis (n = 4), pulmonary arteriovenous malformation (n = 2), graft-versus-host disease (n = 1), and desquamative interstitial pneumonitis (n = 1). Four (20%) patients had thoracic surgical procedures before the transplantation operation. The survival was 80% at a mean follow-up of 2 years. Immunosuppressive drugs included cyclosporine (n = 9) or FK 506 (n = 11) based therapy with azathioprine and steroids. Children were followed up by means of spirometry, transbronchial biopsy, and primed lymphocyte testing of bronchoalveolar lavage fluid. The mean number of treated episodes of rejection was 1.4 at 30 days, 0.5 at 30 to 90 days, and 1.4 at more than 90 days, and the first treated rejection episode occurred on average 28 days after the operation. Obliterative bronchiolitis developed in four (25%) of 16 patients surviving more than 100 days. Results of pulmonary function tests have remained good in almost all recipients. The greatest infectious risk was that of cytomegalovirus: one death and one case of pneumonia. Posttransplantation lymphoproliferative disease was diagnosed in two (12.5%) patients; both recovered. The most common complications were hypertension (25%) and postoperative bleeding (15%). Early results indicate that lung transplantation is a most promising therapy for children with severe vascular and parenchymal lung disease.
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PMID:Pediatric lung transplantation. The years 1985 to 1992 and the clinical trial of FK 506. 767 72


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