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)

To determine the outcome and prognostic factors associated with bone marrow transplantation (BMT), we reviewed the clinical course of 35 adult recipients of such a transplant who were admitted to our intensive-care unit (ICU). This constituted 24% of patients who underwent BMT for treatment of hematologic disorders during the study period. The reasons for admission to the ICU were postsurgical care in 5, respiratory failure in 25, shock in 4, and renal failure in 1. The in-hospital mortality was 20% for the postsurgical patients and 87% for the others. None of the postsurgical patients required mechanical ventilation, whereas 90% of the others did, and the associated mortality was 93%. Infection was the cause of the respiratory failure in all but 3 of the 25 patients and was associated with 95% mortality. Complications that involved multiple organs increased the mortality to 100%. No significant differences were found in age, sex, type of BMT, serologic tests for cytomegalovirus, history of graft-versus-host disease, conditioning regimen for BMT, and duration of stay in the ICU and the hospital between survivors and nonsurvivors. The APACHE II (acute physiology and chronic health evaluation) prognostic scoring system underestimated mortality and had no correlation with the duration of stay in the ICU or the hospital. Vasopressors, total parenteral nutrition, and transfusion of blood components in the ICU had no influence on the outcome. Open-lung biopsy was helpful in making specific diagnoses, and pulmonary artery catheters were used in most patients to guide therapy but did not improve survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Outcome of recipients of bone marrow transplants who require intensive-care unit support. 154 82

A case of thrombotic thrombocytopenic purpura (TTP) is reported in a 40-year-old man 6 months after allogeneic bone marrow transplantation for multiple myeloma. The features of TTP included microangiopathic haemolytic anaemia, severe thrombocytopenia, fluctuating neurological abnormalities, and progressive renal impairment. Despite treatment with anti-platelet agents, prostacyclin infusion, intensive immunosuppression and prolonged plasma exchange, the patient developed end-stage renal failure and is now on maintenance haemodialysis 18 months after the onset of TTP. Graft-versus-host disease and cytomegalovirus infection could not be implicated as aetiological factors, and cyclosporin medication had ceased 1 week before the clinical onset of his disease. The unusually intensive pre-transplant chemotherapy and radiotherapy protocol used in this patient appear to be most likely cause of the generalized endothelial damage resulting in TTP in this patient.
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PMID:A case of thrombotic thrombocytopenic purpura following allogeneic bone marrow transplantation. 229 91

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

We report three cases of haemolytic-uraemic syndrome following bone marrow transplantation in young males. None of them was treated with cyclosporin A. All died in renal failure. Renal histology showed the typical appearances of haemolytic-uraemic syndrome. Immunoperoxidase examination of renal biopsies showed IgM and complement in blood vessels and glomeruli of all three cases. Cytomegalovirus infection was present in two cases and probable in the third. Two cases had been infected with herpes zoster. All had episodes of graft-versus-host disease. Possible pathogenetic mechanisms are discussed.
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PMID:Haemolytic-uraemic syndrome in recipients of bone marrow transplants not treated with cyclosporin A. 353 15

Cyclosporin A has been used in conjunction with allogeneic bone-marrow transplantation in the treatment of 23 patients--21 with acute leukaemia, 1 with chronic granulocytic leukaemia, and 1 with aplastic anaemia. The drug was given twice daily from the day before transplant. At the start of the study cyclosporin prophylaxis was stopped in 3 patients within 44 days of transplantation because of non-specific rashes and/or deteriorating renal function. All 3 patients had acute graft-versus-host disease (GVHD) and died. Thereafter the drug was not stopped because of possible toxic manifestations, and 20 patients have been studied (median follow-up 7 months; maximum 13 months). 2 patients have acquired GVHD; 1 patient died of acute GVHD and 1 has chronic mild disease. 3 other patients have died, 2 of recurrent leukaemia and a third of staphylococcal pneumonia with renal failure. Of the remaining patients, 1 has recurrent leukaemia and 1 has moderately severe renal failure. Several toxic effects of cyclosporin A have been observed but they are mostly reversible and no second malignant neoplasm has developed.
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PMID:Cyclosporin A to prevent graft-versus-host disease in man after allogeneic bone-marrow transplantation. 610 87

35 patients were treated for acute myeloid leukaemia or acute lymphoblastic leukaemia with allogeneic bone-marrow grafts from a parent, child, or sibling who was mismatched at the major histocompatibility complex (MHC). 11 of these patients are alive at least 6 months after grafting, 5 of them after more than 2 years. Of the 15 patients aged under 20 at the time of the graft, 8 are alive and well 6 months to 3 years later. Cyclosporin A was given to all patients after grafting. 1 patient died of acute graft-versus-host disease and in 2 other cases this was a major factor in their death. Graft failure caused the death of 2 patients. 4 patients died of recurrent leukaemia. A fatal complication in 12 patients was pulmonary oedema, often associated with convulsions, intravascular haemolysis, and renal failure. Some of these patients had viral or bacterial infections, but in the majority the syndrome was not associated with demonstrable infection. This syndrome, in which the essential lesion appears to be vascular, was much more common in recipients of mismatched than matched grafts. 3 others died from lung disease in which infection was a factor.
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PMID:Mismatched family donors for bone-marrow transplantation as treatment for acute leukaemia. 613

Cyclosporin-A (CsA) was given to 22 patients who received allogeneic bone marrow transplants as therapy for aplastic anemia and hematologic malignancies. The drug was given daily for 180 days starting with the day of marrow infusion. Engraftment was not impaired and myelotoxicity was not observed. Cutaneous graft-versus-host disease (GVHD) developed in five patients and all either spontaneously resolved or promptly responded to therapy with steroids. Five patients developed systemic GVHD and all responded to therapy with steroids, but only two survived. Interstitial pneumonia was seen in six patients and was fatal in all of them. Liver function abnormalities were seen in 14 patients but could not positively be correlated with CsA administration. Renal function abnormalities were seen in 17 patients. Amphotericin-B therapy contributed significantly to the renal failure. Serum levels of CsA, measured by radioimmunoassay, could not be correlated with the presence of liver or renal function abnormalities. Overall survival so far has been 50.0%. Second malignancies were not observed, but one patient relapsed with leukemia at 343 days.
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PMID:Cyclosporin-A to prevent graft-versus-host disease: a pilot study in 22 patients receiving allogeneic marrow transplants. 633 59

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

The influence of cyclosporine A (CsA) treatment on the development of glomerulonephritis and glomerulosclerosis was investigated in chronic graft-versus-host disease (GvHD), a murine model for lupus nephritis. The renal disease is characterized by the formation of IgG-containing electron-dense deposits along the glomerular basement membrane (GBM) and in the mesangium, followed by the onset of proteinuria which starts, varying per individual mouse, about six weeks after the induction of the disease. Glomerular mRNA levels for matrix molecules were increased from week 4, preceding mesangial matrix expansion and GBM thickening which occurred from week 6. These initial events finally led to development of glomerulosclerosis, and end-stage renal failure. Groups of mice received three intraperitoneal (i.p.) injections per week with different doses of CsA, and treatment was started 2, 4, or 6 weeks after induction of the disease. Treatment with 10 or 50 mg CsA/kg/week did not influence the development of glomerulonephritis or glomerulosclerosis. Injection of 100 mg CsA/kg/week delayed the onset of proteinuria only when treatment was started in week 2. In week 6 some mice had already developed proteinuria whereas others had not. Treatment with 250 mg CsA/kg/week starting in week 6 abrogated glomerulonephritis and glomerulosclerosis only in those animals which were not yet proteinuric at that time. This, despite comparable increased autoantibody levels against DNA, GBM, and renal tubular epithelium (RTE) in both treated and untreated GvHD mice. Further increase in proteinuria and development of glomerulosclerosis could not be prevented if the mice already had developed proteinuria when CsA treatment was started. Dot blot analysis and in situ hybridization showed significantly decreased mRNA levels for alpha 1(I) and alpha 1(IV) collagen in kidneys of CsA-treated mice as compared to those of untreated mice 12 weeks after induction of the disease, if the highest dose of CsA was administered before the onset of proteinuria. No effect on these whole-kidney mRNA levels was observed in mice which had already developed proteinuria before CsA injections were started. Increased mRNA expression for matrix molecules in this group and in untreated GvHD mice was observed mainly in the interstitium. The kidneys of the treated GvHD mice and those of mice injected with 250 mg CsA/kg/week without induction of GvHD showed no morphological signs of CsA nephrotoxicity. We conclude that treatment with 250 mg CsA/kg/week prevents the development of glomerulonephritis and glomerulosclerosis in this model of lupus nephritis, if started before the onset of proteinuria.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prevention of glomerulosclerosis by early cyclosporine treatment of experimental lupus nephritis. 770 25

The crucial first step in management of multiple myeloma is to be certain regarding the diagnosis. Multiple myeloma must be distinguished from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma. Therapy should be administered to patients with advanced and active myeloma involving anemia, osteolysis or renal failure. Chemotherapy with a single agent (melphalan) is the preferred initial treatment for overt, symptomatic multiple myeloma. Cytostatic drug combinations produce a higher response rate, but survival and remission during are the same compared with melphalan/prednisone therapy. However, in patients with renal failure and/or poor prognostic factors (advanced stage, elevated beta 2-microglobulin, high bone marrow plasma cell labeling index, high levels of C-reactive protein and lactate dehydrogenase and/or nodular pattern of bone marrow infiltration), combined treatment with adriamycin, vincristine and prednisone should be administered to prevent nephrotoxicity and attain a rapid paraprotein decrease. Alpha interferon treatment as maintenance seems to prolong the duration of the plateau state after response to chemotherapy, but apparently does not prolong survival. Allogeneic bone marrow transplantation involves significant early mortality (50%); the risk of graft versus host disease, infections and renal failure is a problem, and relapse is common. High dose chemotherapy followed by autologous bone marrow transplantation or peripheral blood stem cell reinfusion may prolong survival and free time to progression, but, to date, there are no indications of cure. This therapeutic procedure, therefore, should be considered for randomized trials for young patients with poor prognostic factors.
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PMID:[Diagnosis and therapy of multiple myeloma: current aspects]. 789 48


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