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)

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

We examined the effect of methotrexate (MTX) combined with cyclosporine (CSP) on the prevention of graft-versus-host disease (GVHD) in dogs. Ten recipients were prepared for grafting with 9 Gy of total-body irradiation and given marrow and buffy coat cells from littermate donors differing for one DLA haplotype (AA leads to AB or AB leads to AC). MTX (0.4 mg/kg) was given i.v. on days 1, 3, 6, and 11. CSP was given i.m. on days 0 to 7 and orally on days 8 to 100. The dose was 15 mg/kg/day on days 0 to 25, 10 mg/kg/day on days 26 to 50, 5 mg/kg/day on days 51 to 75, and 5 mg/kg every other day on days 75 to 100. All ten dogs had sustained engraftment. Three dogs died, one with pneumonia (day 57), one with pneumonia and GVHD (day 107), and one with convulsions (day 204). Seven dogs are surviving at 210 to 493 days, and all are complete chimeras; five are well and two have chronic GVHD that developed after immunosuppressive treatment had been stopped. These results with a combination of MTX and CSP as GVHD prophylaxis are superior to those obtained previously with MTX alone in dogs given marrow grafts from DLA-haploidentical littermates.
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PMID:Combined immunosuppression with cyclosporine and methotrexate in dogs given bone marrow grafts from DLA-haploidentical littermates. 636 90

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

Leukoencephalopathy probably caused by tacrolimus hydrate after stem cell transplantation in a girl with MDS 7 monosomy is reported. The conditioning regimen consisted of thiotepa (150 mg/m2 x 4), melphalan (70 mg/m2 x 2) and 12 Gy total body irradiation. She received peripheral blood CD34 positive cells (4.17 x 10(6)/kg) from her HLA-mismatched father and tacrolimus hydrate was used for GVHD prophylaxis. Engraftment was rapid and grade 1 acute GVHD of the skin responded well to pulse therapy. From day 27 she became irritable and sleepless, and right facial convulsions developed on day 37. No abnormality was found in the cerebrospinal fluid. Cranial CT findings showed no abnormalities except for low density lesions around the bilateral ventricle. Leukoencephalopathy was suspected and tacrolimus hydrate was discontinued. Thereafter psychosomatic symptoms improved, temporarily however, similar symptoms again developed following cyclosporine administration. Therefore we had to halt the administration of both tacrolimus and cyclosporine. She died on day 104 because of GVHD and fungal infection without recovering from leukoencephalopathy.
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PMID:[Leukoencephalopathy probably caused by tacrolimus hydrate after stem cell transplantation in a girl with MDS 7 monosomy]. 926 67

A 40-year-old woman underwent allogeneic peripheral blood stem cell transplantation for relapsed AML-M6. She developed graft-versus-host disease on day +15 post-transplant, for which she was treated with cyclosporin A and methyl prednisolone. On day +19 she developed cortical blindness, headache and convulsions which were associated with white matter changes on MRI scanning of the head and elevated cyclosporin A levels. A diagnosis of cyclosporin A encephalopathy was made and cyclosporin A was discontinued. Her vision recovered completely after 48 h and the other symptoms resolved. This is the first case of cyclosporin A encephalopathy to be reported in an allogeneic PBSC recipient.
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PMID:Reversible cortical blindness and convulsions with cyclosporin A toxicity in a patient undergoing allogeneic peripheral stem cell transplantation. 938 85

We analyzed the incidence of neurological complications in 77 patients receiving stem cell transplantation (SCT), and 12 patients (15.8%) had the following symptoms: convulsions, intracranial hemorrhage, and leukoencephalopathy. Although statistically not significant, neurological complications were seen more frequently in patients after allogeneic transplantation, and in those with acute graft-versus-host disease (GVHD) exceeding grade II. The most significant risk factor for neurological complications was identified as unrelated donor allogenic transplantation (P = 0.016). Complications were categorized into three groups, based on time of onset and symptoms: (1) convulsions during the conditioning period, (2) intracranial hemorrhage during the period of granulocyte recovery, and (3) leukoencephalopathy at around 2 months after SCT. We propose awareness of the risks of neurological complications in each period after SCT so that immediate and effective treatment of patients can be instigated.
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PMID:Neurological complications after stem cell transplantation in childhood. 1049 Jul 31

A 25-year-old woman with severe aplastic anemia received allogeneic bone marrow transplantation from an HLA-identical sibling. Pretransplant conditioning comprised 3.6 Gy of total body irradiation and 200 mg/kg cyclophosphamide. Cyclosporine (CSP) and methotrexate were administered to prevent graft-versus-host disease (GVHD). The patient complained of severe headache soon after CSP administration on day-1. On day 3, convulsion developed and she lost consciousness for 15 min. CT and MRI demonstrated low density areas and high signals, respectively, in the frontal and parietooccipital lobes and splenium of the corpus callosum, suggesting brain edema probably induced by CSP. After immediate withdrawal of CSP, glycerol and prednisolone were instituted, and the patient's condition improved. Thereafter, she developed grade II acute GVHD. This was treated with tacrolimus, which produced no adverse effects including central nervous system (CNS) toxicity. This case illustrates that careful management of CNS disorders induced by CSP can be important in patients undergoing allogeneic bone marrow transplantation.
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PMID:[Tacrolimus administration to a patient with cyclosporine-induced encephalopathy after allogeneic bone marrow transplantation]. 1102 Sep 82

We report a case of cerebral hemorrhage associated with cyclosporin A (CsA)/FK506-related encephalopathy that developed in a 16-year-old woman after allogeneic bone marrow transplantation. Hematopoietic engraftment occurred on day 15, and the patient developed systemic convulsions after CsA was replaced by FK506 for the treatment of acute graft-versus-host disease (GVHD). Based on magnetic resonance imaging, laboratory findings and cerebrospinal fluid studies, she was diagnosed as having CsA/FK506-related encephalopathy with cerebral hemorrhagic infarction. Although she recovered completely after discontinuation of FK506, she developed convulsions again 15 days after re-administration of FK506. A computed tomography scan showed cerebral hemorrhage. She died of respiratory failure. Vascular damage induced by immunosuppressive drugs and enhanced by acute GVHD seemed to be the cause of the cerebral hemorrhage. Since hypertension, which was present during both of the central nervous system events, seemed to have contributed to the development of the cerebral hemorrhage, it is proposed that CsA and FK506 should be reduced or discontinued when patients who have risk factors of hypertension become hypertensive even if they have no symptoms of neurotoxicity.
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PMID:Fatal cerebral hemorrhage associated with cyclosporin-A/FK506-related encephalopathy after allogeneic bone marrow transplantation. 1110 Jul 53

Human herpesvirus (HHV)-6 was discovered 15 years ago and was then grouped as a member of the family human herpesviridae. Its first clinical manifestation was identified 2 years later as the agent responsible for exanthem subitum. With the advent of newer molecular techniques, its diagnosis is easier and prospective studies have shown that it is the most common pathogen responsible for febrile illness in infants. In some infants, it is associated with febrile convulsions. Two subtypes, A and B, have been identified, B subtype commonly being responsible for primary infection in infants. Primary infection in healthy adults is rare. Most of the clinical manifestations are mild, self-limiting and rarely fatal. Reactivation of HHV-6 is frequently found in bone marrow as well as solid organ transplant recipients. HHV-6 has been shown to be an independent risk factor responsible for recurrence of cytomegalovirus infection, especially in solid organ transplants. In bone marrow transplant recipients, HHV-6 has been associated with various manifestations like marrow suppression and graft versus host disease, although most infections present as usually mild febrile illness with or without rash. It has been reported to cause encephalitis in transplant recipients. Although HHV-6 has been shown to be responsible for upregulation of HIV in vitro studies, its exact role in AIDS is yet to be defined. In addition to its neurotropic manifestation of febrile convulsion in infancy, it has been found in plaques in the brain of multiple sclerosis and progressive multifocal leukoencephalopathy. Further studies are needed before its role in the pathogenesis of these neurological illnesses can be established. Its lymphotropic feature was responsible for its discovery and now it has only been detected in some lesions of primary ocular mucosa associated lymphoid tissue lymphoma. As HHV-6 is found to be responsible for more and more illnesses, especially causing serious illnesses in the immunocompromised, it is becoming necessary to find effective treatment. Some agents, like cidofovir and phosphonoformic acid, are effective in in vitro studies and some have shown effectiveness in a clinical setting. Further studies are needed to identify its role in the pathogenesis of various neurological and malignant lesions and AIDS. Various treatment regimens should be tested in clinical scenario and especially in immunocompromised transplant recipients.
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PMID:Human herpesvirus 6: its impact and influence on infectious diseases and their management. 1133 81

A 21-year-old woman with severe aplastic anemia received an allogeneic bone marrow transplant (allo-BMT) from an HLA-matched and ABO-matched sibling donor after conditioning with cyclophosphamide, rabbit ATG (Lymphoglobuline; Aventis-Pharma), and total lymphoid irradiation. She had a long history of cyclosporin A (CsA) therapy before conditioning. She complained of severe headache and convulsions on day 0, and findings on magnetic resonance images suggested CsA-induced encephalopathy. CsA was immediately stopped, and tacrolimus for prevention of graft-versus-host disease (GVHD) was started on day 2. Hematological engraftment was observed on day 14 without serious GVHD. Prompt diagnosis, replacement of immunosuppressive agents, and careful monitoring of serum drug concentrations are thought to have contributed to the patient's good clinical course, since CsA-induced encephalopathy tends to be recurrent but to improve completely without any sequelae.
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PMID:Cyclosporin A-induced encephalopathy after allogeneic bone marrow transplantation with prevention of graft-versus-host disease by tacrolimus. 1170 97


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