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)

Bone marrow transplantation was performed on a 15 year old girl with chronic myelogenous leukemia. The bone marrow was obtained from her younger sister, who was human leukocyte antigen haplo-identical but major ABO incompatible. As a result, the condition of pure red cell aplasia (PRCA) persisted over a long period of time. In order to overcome major ABO incompatibility, erythrocytes were eliminated from the bone marrow graft before transplantation, and methotrexate and cyclosporine (CsA) were used to prevent graft-versus-host disease (GVHD). Administration of erythropoietin proved ineffective. B19 parvovirus infection could not be detected during that time. Agglutinin titers decreased to less than fourfold in parallel with the recovery of erythrocytes. Reports on similar PRCA have been limited to cases of transplantation with ABO incompatibility and cases where CsA was administered to prevent GVHD. This suggests that ABO incompatibility and CsA might be related to the development of PRCA.
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PMID:Long duration of erythrocyte hypoplasia after bone marrow transplantation. 141 39

We report a patient who had abrupt onset of pure red cell aplasia (PRCA) induced by B19 parvovirus during allogeneic bone marrow transplantation (BMT). A 14-year-old girl with APL in complete remission was admitted in February 1988, for the purpose of BMT. She was received marrow from HLA identical sister on March 17, 1988 (day 0). She received 120 mg/kg cyclophosphamide and 12 Gy total body irradiation for conditioning of BMT. For graft-versus-host disease (GVHD) prophylaxis she was given cyclosporine and short term methotrexate. She did not develop acute GVHD after BMT, but on the day 28 a bone-marrow aspirate revealed findings of PRCA. During this course the number of white blood cell and platelet favorably recovered. B 19 parvovirus DNA was detected in the serum of the day 30 and day 42. Antihuman B 19 parvovirus (HPV) antibody titers were increased: the values of anti-HPV IgM were suddenly elevated and those of anti-HPV IgG were elevated. Serum on the day 42 inhibited erythroid progenitors (CFU-E, BFU-E) but not inhibited myeloid progenitors (CFU-C). A reticulocyte count recovered on the day 50. As the patient was HPV-IgG negative prior to BMT and the donor was HPV-IgG seronegative, the source of infection may be platelet transfusion (day 7 through 14).
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PMID:[Pure red cell aplasia induced by B19 parvovirus during allogeneic bone marrow transplantation]. 217 87

We determined the serum levels of tumor necrosis factor-alpha (TNF) in allogeneic bone marrow transplant recipients in order to evaluate the relationship between TNF and graft-versus-host disease (GVHD). Eight patients with acute leukemia receiving an HLA-identical marrow graft were studied. Samples from healthy subjects and pretransplant recipients were all negative for TNF. Six of eight patients had detectable levels of TNF in serum after transplantation. All three patients with acute GVHD, and three of five patients without acute GVHD had elevated TNF levels in serum. Among the patients with increased TNF levels, documented infection was demonstrated in only one patient, with a clinical diagnosis of B19 parvovirus infection. Serum TNF levels were elevated when the WBC counts were more than 2,000/microliters. However, serum concentrations of TNF significantly correlated with body temperature. Although we could not conclude definitely that serum TNF levels correlated with severity of GVHD, it was suggested that TNF may be produced as a result of latent infections or immunological reaction against non-HLA allogeneic antigens.
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PMID:Serum tumor necrosis factor-alpha levels in allogeneic bone marrow transplant recipients with acute leukemia. 262 65

The clinical characteristics and outcome of posttransplantation aplastic anemia (AA) were determined in 12 of 1,736 patients (0.007%) undergoing orthotopic liver transplantation (OLT) that were afflicted with AA. None of the affected patients had a history of hematologic disease. Median patient age was 53 years (range, 2-61 years); 10 of the affected patients were men, and 2 were women. The etiologies of AA included non-A, non-B, non-C fulminant hepatic failure (FHF) (3 patients), graft-versus-host disease (4 patients), Parvovirus-induced (1 patient), and idiopathic (4 patients). The median duration between OLT and the onset of AA was 12 days (range, 11-14 days) in the 3 patients undergoing OLT for FHF; in contrast, AA developed in the other 9 patients at 37 days (range, 27-51 days) after OLT. Eleven patients were treated with reduction of their cyclosporine or tacrolimus dosage, granulocyte colony-stimulating factor, anti-thymocyte globulin, and Solumedrol. Two of the 3 patients developing AA following OLT for FHF achieved hematologic recovery 21 and 92 days after diagnosis. In contrast, all 9 non-FHF patients developing AA after OLT died, 5 due to infectious complications and 4 following intracranial bleeding. AA is an unusual complication of OLT. In the setting of FHF, it affects young males in the early posttransplantation period, and, when infectious complications can be avoided, remission and stable allograft function can be anticipated. However, in the non-FHF patient, AA occurs in older individuals later in the posttransplantation period and has a uniformly poor outcome.
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PMID:Aplastic anemia complicating orthotopic liver transplantation. 932 6

Fifth (erythema infectiosum) and sixth (roseola infantum) diseases are common rash illnesses of childhood that have long been recognized in clinical medicine. The discovery of the viruses that cause these illnesses has revealed relationships with other syndromes. Primary infection with the agent of erythema infectiosum, human parvovirus B19, is associated with transient aplastic crisis in hemolytic anemia, arthropathy in adults, chronic anemia in immunocompromised patients, and nonimmune fetal hydrops in pregnant women. The only documented illness associated with primary infection with human herpesvirus 6 is roseola or exanthema subitum in young children. However, reactivated infections in adults and immunocompromised patients may be associated with serious illness such as encephalitis/encephalopathy, and bone marrow suppression leading to transplant failure or graft-versus-host disease. Diagnostic studies for both viruses have been limited, although reliable serologic tests for human parvovirus B19 have recently become available. Diagnosis of human herpesvirus 6 remains problematic, because current tests cannot differentiate primary from reactivated disease. This is more of an issue for the putative relationship of these viruses to more chronic conditions, such as rheumatologic disease for human parvovirus B19 and multiple sclerosis for human herpesvirus 6. The relationship between the viruses and these conditions remains controversial, and better diagnostic tests and further information on viral pathogenesis for both viruses are required in order to make a reliable judgment in this regard.
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PMID:Fifth (human parvovirus) and sixth (herpesvirus 6) diseases. 1196 54

We describe two patients with acute myeloid leukemia successfully treated with anti-CD20 antibody for pure red cell aplasia (PRCA) following ABO-mismatched allogeneic hematopoietic stem cell transplantation (HSCT). PRCA following HSCT is associated with major ABO incompatibility between donor and recipient and is due to an inhibition of donor erythroid precursors by residual host isoagglutinins. The first patient developed PRCA resistant to several treatment options including donor-derived leukocyte infusions (DLI), high-dose erythropoietin (EPO), and rapid tapering of cyclosporin A (CsA). This patient also received anti-viral therapy as CMV and parvovirus B19 infections were regarded as additional causes of PRCA. Due to a loss of donor chimerism, he underwent second HSCT, but PRCA still persisted. He showed no evidence of graft-versus-host disease (GVHD). Finally he was administered anti-CD20 antibody (rituximab) at a dose of 150/m2 and PRCA resolved in a short period of time. The case was complicated by life-threatening pulmonary aspergillosis with septic shock, successfully treated with anti-fungal therapy. The second case concerns a patient, who revealed PRCA after major ABO-incompatible HSCT from his brother. Considering our experience with the previously described patient, he proceeded to rituximab at a dose of 150/m2 as first line treatment. We observed rapid recovery from PRCA without any side effects. We conclude that rituximab seems to be a promising therapeutic option in patients with PRCA after ABO-mismatched HSCT, in whom conventional treatment fails.
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PMID:Successful treatment of pure red cell aplasia with repeated, low doses of rituximab in two patients after ABO-incompatible allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia. 1626 24

Chimerism and graft-versus-host disease (GVHD) pose significant risks to liver transplant patients. The risk of chimerism and GVHD is higher among cases of living-related liver transplant (LRLT). Donors homozygous at all HLA loci carry a higher risk for GVHD. Herein we present a case of LRLT. The recipient suffered from end-stage liver disease and received a right lobe graft from his son. After 8 months posttransplant, the patient developed profound bone marrow depression. The patient was negative for CMV, Brucella, HHV6, HHV8, HBV, HCV, and parvovirus. No skin or GI signs of GVHD were noted. The patient and donor were HLA typed by SSP. The donor was homozygous for all HLA loci while the patient shared the class II homozygosity and was class I heterozygous. Chimerism studies were prompted after noting that the neutrophil compartment of the patient was homozygous for all HLA loci. This initiated further studies of the PMN and lymphocytes by microsatellite analysis. A total 15 microsatellites were analyzed. The results suggest that the majority (75%) of the PMNs and 45% of the lymphocytes were of donor origin. The patient was treated with G-CSF; his WBC counts returned to normal. At 2.5 years posttransplant the patient had not developed GVHD, despite the large number of donor lymphocytes circulating in his bloodstream. The only complaint he had was severe arthritis, which was treated with steroids. It must be investigated whether this was the result of GVHD.
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PMID:Neutrophils and lymphoid chimerism after adult living-related liver transplantation from a homozygous donor. 1638 27

Multipotent mesenchymal stromal cells (MSCs) are used to improve the outcome of hematopoietic stem cell transplantation (HCST) and in regenerative medicine. MSCs may harbor persistent viruses that may compromise their clinical benefit, however. Retrospectively screened, 1 of 20 MSCs from healthy donors contained parvovirus B19 (B19) DNA. MSCs express the B19 receptor (P antigen/globoside) and a co-receptor (Ku 80) and can transmit B19 to bone marrow cells in vitro, suggesting that the virus can persist in the marrow stroma of healthy individuals. Two patients undergoing HSCT received the B19-positive MSCs as treatment for graft-versus-host disease; neither developed viremia nor symptomatic B19 infection. These findings demonstrate for the first time that persistent B19 in MSCs can infect hematopoietic stem cells and underscore the importance of monitoring B19 transmission by MSC products.
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PMID:Persistence of human parvovirus B19 in multipotent mesenchymal stromal cells expressing the erythrocyte P antigen: implications for transplantation. 1880 48

Canine parvovirus type 2a (CPV-2a) is a variant of CPV-2, which is a highly contagious pathogen causing severe gastroenteritis and death in young dogs. However, how CPV-2 participates in cell regulation and immune response remains unknown. In this study, persistently infected MDCK cells were generated through culture passage of the CPV-2a-infected cells for ten generations. Our study showed that CPV-2a induces cell proliferation arrest and cell morphology alternation before the fourth generation, whereas, the cell morphology returns to normal after five times of passages. PCR detection of viral VP2 gene demonstrated that CPV-2a proliferate with cell passage. An immunofluorescence assay revealed that CPV-2a particles were mainly located in the cell nuclei of MDCK cell. Then transcriptome microarray revealed that gene expression pattern of MDCK with CPV-2a persistent infection is distinct compared with normal cells. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genome pathway analysis demonstrated that CPV-2a infection induces a series of membrane-associated genes expression, including many MHC protein or MHC-related complexes. These genes are closely related to signaling pathways of virus-host interaction, including antigen processing and presentation pathway, intestinal immune network, graft-versus-host disease, and RIG-I-like helicases signaling pathway. In contrast, the suppressed genes mediated by CPV-2a showed low enrichment in any category, and were only involved in pathways linking to synthesis and metabolism of amino acids, which was confirmed by qPCR analysis. Our studies indicated that CPV-2a is a natural immune activator and has the capacity to activate host immune responses, which could be used for the development of antiviral strategy and biomaterial for medicine.
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PMID:Transcriptome profiling indicating canine parvovirus type 2a as a potential immune activator. 2733 28

Hematological malignancies are treated with intensive high-dose chemotherapy, with or without radiation. This is followed by hematopoietic stem cell (HSC) transplantation (HSCT) to rescue or reconstitute hematopoiesis damaged by the anticancer therapy. Autologous HSC grafts may contain cancer cells and purging could further improve treatment outcomes. Similarly, allogeneic HSCT may be improved by selectively purging alloreactive effector cells from the graft rather than wholesale immune cell depletion. Viral agents that selectively replicate in specific cell populations are being studied in experimental models of cancer and immunological diseases and have potential applications in the context of HSC graft engineering. This review describes preclinical studies involving oncolytic virus strains of adenovirus, herpes simplex virus type 1, myxoma virus, and reovirus as ex vivo purging agents for HSC grafts, as well as in vitro and in vivo experimental studies using oncolytic coxsackievirus, measles virus, parvovirus, vaccinia virus, and vesicular stomatitis virus to eradicate hematopoietic malignancies. Alternative ex vivo oncolytic virus strategies are also outlined that aim to reduce the risk of relapse following autologous HSCT and mitigate morbidity and mortality due to graft-versus-host disease in allogeneic HSCT.
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PMID:The ex vivo purge of cancer cells using oncolytic viruses: recent advances and clinical implications. 2751 66


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