Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel immunosuppressant, succinyl acetone (4,6-dioxoheptanoic acid), was studied in dogs. Results with bolus intravenous injections at doses ranging from 50 to 1600 mg/kg showed dose-dependent alpha and beta half-lives, ranging from 30 to 80 min and 7 to 27 hr, respectively. Results suggested that continuous i.v. infusion was necessary to maintain constant plasma levels. Four dogs were given 9.2 Gy total-body irradiation and autologous marrow transplants along with continuous i.v. infusion of succinyl acetone at 50, 100, 200, or 400 mg/kg/day for 21 days, and all four had rapid, sustained hematopoietic engraftment. However, two of the four dogs receiving 200 and 400 mg succinyl acetone/kg/day, respectively, developed bilateral hind-limb ataxia, with histologically confirmed cerebellar lesions in the dog given the higher dose, thus establishing a potential dose-limiting neurotoxicity. Prevention of graft-versus-host disease was studied in recipients of allogeneic marrow. Dogs were given 9.2 Gy TBI, followed by hematopoietic grafts from unrelated DLA-nonidentical or DLA-haploidentical littermate dogs. Succinyl acetone was given as continuous infusion for 21 days after transplant at doses of 100-300 mg/kg/day. Starting succinyl acetone on the day of marrow infusion in four dogs failed to prevent rapid onset of acute GVHD, and dogs survived no longer than controls. Starting succinyl acetone 3 days before transplant delayed the onset of acute GVHD and prolonged survival significantly compared with that of dogs not given postgrafting immunosuppression (P = 0.008); survival was comparable to that in previously reported dogs given either methotrexate or cyclosporine as postgrafting immunosuppression (P = 0.88 and 0.99, respectively). Seven of the sixteen allogeneic recipients developed evidence of neurotoxicity during succinyl-acetone infusion. Neurological dysfunctions were manifested by hind-limb ataxia and posterior paresis. In conclusion, succinyl acetone significantly delayed the onset of GVHD and prolonged survival of DLA-nonidentical marrow graft recipients but did not induce graft-host tolerance and was associated with dose-limiting neurotoxicity.
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PMID:Pharmacologic, toxicologic, and marrow transplantation studies in dogs given succinyl acetone. 144 Aug 68

Allogeneic bone marrow transplantation (BMT) was successfully performed in four Chediak-Higashi (CHS) syndrome affected cats. Preparatory regimens included selective intestinal flora decontamination, fractionated total body irradiation for myeloablation, and prophylactic treatment for graft-versus-host disease with cyclosporin A. Neutrophil chemotaxis under-agarose and whole-blood platelet aggregation/secretion were characterized prior to BMT and after engraftment of donor-origin marrow cells. Liver and kidney biopsies were obtained and evaluated by light and electron microscopy before, and at 6 months post-BMT to determine what effect BMT might have on abnormal lysosome fusion in hepatocytes and renal tubule cells. The platelet storage pool defect was resolved by day 40 post-BMT. In vitro neutrophil migration in all cats appeared to improve with time after BMT and complete restoration was evident by day 175 post-BMT. No apparent differences were evident in either the liver or the kidney at 6 months post-BMT. One cat developed seizures and one developed posterior paresis 5 months post-BMT; neurologic impairment ultimately resulted in death of two cats at 6 and 8 months post-BMT, respectively. Neurologic lesions in both cats were characterized by non-suppurative encephalitis. Allogeneic BMT successfully corrected the neutrophil migration defect and platelet storage pool deficiency but had no effect on lysosome distribution in liver and kidney cells of CHS cats.
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PMID:Restoration of neutrophil and platelet function in feline Chediak-Higashi syndrome by bone marrow transplantation. 207 Jan 46

A 16-year-old girl developed a pain and paresis in the right hip joint in April 1994. Abdominal CT scan revealed hepatosplenomegaly and large tumor mass (6 x 7 x 13 cm) invading the right psoas muscle in the pelvic cavity. Laboratory data disclosed marked granulocytosis, the presence of Ph1 translocation and bcr-abl rearrangement, thus a diagnosis of CML was made. The tumor was shown to be consisted of granulocytes at all stages of development by a fine needle aspiration cytology. According to the criteria of IBMTR, the disease was classified as accelerated phase solely because the sum of myeloblasts and promyelocytes exceeded over 20%. The patient was treated with hydroxycarbamide, 6MP and dexamethasone, and marked reduction of the tumor mass was observed. Then an allogeneic BMT was performed from her HLA- identical brother on August 1994. She did not develop clinically significant symptoms except for grade I skin GVHD. The tumor was completely disappeared after the BMT as assessed by the abdominal CT scan. No cytological and chromosomal relapse has been observed for 20 months after the BMT.
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PMID:[An allogeneic bone marrow transplantation for chronic myelocytic leukemia with a large extramedullary tumor in the pelvic cavity]. 891 72

Monoclonal antibodies are increasingly being incorporated in conditioning regimens for autologous or allogeneic hematopoietic cell transplantation (HCT). The benefit of adding rituximab to autologous HCT regimens is purportedly related to in vivo purging of clonal B cells. Randomized trials comparing the addition (or not) of rituximab to high-dose therapy regimens are lacking. No benefit of standard-dose radioimmunotherapy-based regimens for autografting in aggressive lymphomas was seen in a randomized controlled study. The incorporation of rituximab into allogeneic HCT regimens aims to improve responses while reducing nonrelapse mortality resulting from acute graft-versus-host disease. The optimal dose and administration schedule of rituximab in this setting are unknown, and potentially serious complications from increased infections owing to prolonged (and profound) cytopenias or persistent hypogammaglobulinemia are of concern. Radioimmunotherapy-based conditioning for allografting holds promise as a modality to optimize tumor control and synergize adoptive immunotherapy effects, but it remains experimental at this time. The addition of alemtuzumab to allogeneic HCT regimens is associated with prolonged lymphopenia and impaired immune reconstitution, high relapse rates, and serious infections. The optimal dose and schedule of alemtuzumab to avoid prolonged immune paresis remain elusive. It is anticipated that additional monoclonal antibodies will soon become available that can be incorporated into HCT regimens after safety and clinical efficacy are demonstrated.
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PMID:Monoclonal antibodies in conditioning regimens for hematopoietic cell transplantation. 2361 18