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 herein a 21-year-old hepatitis B virus (HBV) female carrier who developed persistent fever, lymphadenopathy and pancytopenia in September of 2000. Hemophagocytes were found in the bone marrow smears. Epstein-Barr virus (EBV) serology showed positive for VCA-IgG, IgM and EB-ER and negative for EBNA. The EBV genome was detected in the peripheral blood. The patient was diagnosed as having EBV-associated hemophagocytic syndrome (EBV-AHS) and received chemotherapy. Although she was treated with lamivudine three months after the initiation of chemotherapy, she developed severe hepatitis. She recovered from the hepatitis through a combination of plasma exchange, immunosuppressive and antiviral therapies. Because of the refractoriness of her EBV-AHS to chemotherapy, she received allogeneic peripheral blood stem cell transplantation (PBSCT) from her HLA-identical brother. Hepatitis B did not recur after the PBSCT under administration of lamivudine. The EBV genome in the peripheral blood disappeared soon after the PBSCT but it was revealed again after the initiation of prednisolone for the treatment of acute GVHD. A donor lymphocyte infusion (DLI) was given on day 169 and the EBV genome copy number in the peripheral blood gradually decreased and disappeared. Although the origin of the EBV-infected cells could not be determined as being from the host or donor, DLI was a useful treatment for the recurrence of EBV infection after allogeneic stem cell transplantation for EBV-AHS.
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PMID:[Allogeneic peripheral blood stem cell transplantation for a hepatitis B virus carrier with Epstein-Barr virus associated with hemophagocytic syndrome]. 1519 50

Selective depletion of alloreactive T cells from allogeneic stem cell grafts can reduce graft-versus-host disease (GVHD) while preserving beneficial effects of T cells including facilitation of engraftment, protection against opportunistic infection, and reduced relapse risk. Memory T cells (CD62L(-)) represent a population of T cells that have previously encountered pathogens and may contain fewer T cells capable of recognizing neoantigens including recipient allogeneic antigen (aAg). We investigated whether human naive (CD62L(+)) or memory (CD62L(-)) T cells had different capacities to respond to aAg by assessing their ability to proliferate in response to and lyse HLA-mismatched Epstein-Barr virus-transformed B cells. Freshly sorted and in vitro expanded CD62L(-) memory T cells were less responsive to aAg stimulation than were CD62L(+) naive T cells but contained higher levels of cytomegalovirus (CMV)-specific T cells. Analysis of T cell receptor (TCR) repertoire showed restricted TCR diversity in the memory T-cell population possibly due to selection associated with chronic exposure to common pathogens. Memory T cells may represent a donor cell subpopulation suitable for enhancing immune reconstitution without increasing the risk of GVHD.
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PMID:Human CD62L- memory T cells are less responsive to alloantigen stimulation than CD62L+ naive T cells: potential for adoptive immunotherapy and allodepletion. 1523 69

Acute graft-versus-host disease, a major obstacle to the overall success of allogeneic hematopoietic stem cell transplantation, is primarily induced by a subset of donor T cells. Most strategies to prevent acute graft-versus-host disease target all T cells regardless of their specificity, and this leads to prolonged posttransplantation immunodeficiency. Selective depletion of alloreactive T cells could spare protective immunity and facilitate engraftment and graft-versus-leukemia effects. Recently described depletion strategies target activation markers such as CD25 that are expressed by alloreactive T cells. However, incomplete depletion may occur when a single surface epitope or pathway of apoptosis is targeted that may not be fully and concurrently expressed among all alloreactive cells. We now report on a novel strategy effective in both cord blood and peripheral blood stem cell alloreactive T cells that simultaneously induces 2 independent pathways of apoptosis after stimulation by recipient dendritic cells or Epstein-Barr virus-transformed B cells. First, we demonstrate that the folate antagonist trimetrexate selectively depletes proliferating alloreactive precursors in vitro in a dose- and time-dependent manner. Similarly, a second agent, denileukin diftitox, kills activated alloreactive T cells expressing CD25. Most importantly, these 2 agents can exert their effects in concert with superior efficacy while sparing resting bystander T cells, which remain available to mount antimicrobial or third-party responses.
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PMID:Superior depletion of alloreactive T cells from peripheral blood stem cell and umbilical cord blood grafts by the combined use of trimetrexate and interleukin-2 immunotoxin. 1550 8

A 34-year-old woman was admitted for chronic graft-versus-host disease ten months after an unrelated bone marrow transplantation. Cytomegalovirus (CMV) antigenemia on day 5 of hospitalization was negative. Thrombocytopenia occurred on day 9. Laboratory findings revealed severe liver dysfunction on day 13. On day 14, the patient developed interstitial pneumonia and disseminated intravascular coagulation, and died from progressive respiratory failure. Multinucleated giant cells were found in the lung, liver, spleen, esophagus, pancreas and intestine obtained at autopsy. Varicella-zoster virus (VZV) was detected in the blood using the polymerase chain reaction (PCR) technique. CMV, herpes virus type 6 and Epstein-Barr virus were detected in the liver and lung with the PCR technique. We concluded visceral VZV infection was the main cause of her death because of her aggressive clinical course and the histology at autopsy. In this case, chronic GVHD and its immunosuppressive treatment resulted in her fatal VZV reactivation.
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PMID:[Fatal acute visceral disseminated varicella-zoster virus infection in a patient with chronic graft-versus-host disease]. 1551 Aug 35

In patients with hematological malignancies receiving HLA-matched stem cell transplantation, T cells specific for minor histocompatibility antigens play a major role in graft rejection, induction of graft-versus-host disease and beneficial graft-versus-leukemia reactivity. Several human minor histocompatibility antigens recognized by T cells have been identified, but only two are presented by HLA class II molecules. In search of an efficient approach to identify antigenic peptides processed through the HLA class II pathway, we constructed a cDNA library in bacteria that were induced to express proteins. Bacteria were opsonized with complement to enforce receptor-mediated uptake by Epstein-Barr virus immortalized B cells that were subsequently used as antigen-presenting cells. This approach was validated with an HLA class II-restricted antigen encoded by gene DBY. We were able to identify bacteria expressing DBY diluted into a 300-fold excess of bacteria expressing a nonrelevant gene. Screening of a bacterial library using a DBY-specific CD4 T cell clone resulted in the isolation of several DBY cDNAs. We propose this strategy for a rapid identification of HLA class II-restricted antigenic peptides recognized by CD4 T cells.
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PMID:A novel approach to identify antigens recognized by CD4 T cells using complement-opsonized bacteria expressing a cDNA library. 1552 18

Haploidentical stem cell transplantation has became a clinical reality in the last 10 years as it provides the chance of transplant for about 50% of patients with hematological malignancies who do not have a matched related or unrelated donor. Proper graft preparation for this type of transplant is crucial and this paper analyses our work over the past decade in the search for the optimal graft processing procedure moving from E-rosetting and soybean agglutination, through a combination of negative or positive selection of hematopoietic stem cells to the current method of one-step positive selection. In preparing a graft for haploidentical transplant, three essential requisites must be met. It must contain (1) a megadose (>10 x 10(6) x kg recipient b.w.) of hematopoietic stem cells to overcome the HLA histocompatibility barrier; (2) very few T-lymphocytes (CD3+ cells < 3 x 10(4)/kg recipient b.w.) to prevent severe acute and chronic graft-versus-host disease (GvHD); (3) very few B-lymphocytes to prevent Epstein-Barr virus-related lymphoproliferative disorders. With current graft processing technologies based on positive selection of hematopoietic stem cells, these requirements can be met. A 70-80% hematopoietic stem cell recovery ensures the target megadose is achieved in over 70% of cases with a T-cell depletion of more than 4 logs and a B-cell depletion of over 3 logs. Progress in graft processing has ensured primary, sustained engraftment rates of over 90% and has significantly reduced the incidence of severe acute GvHD and EBV-related lymphoproliferative disorders. Modern time-saving automated graft processing devices ensure reproducibility, reliability, and biological safety, which make widespread application of the haploidentical transplant currently feasible.
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PMID:Graft engineering for allogeneic haploidentical stem cell transplantation. 1552 44

Antilymphocyte/thymocyte globulins (ALGs/ATGs) have now been used for over 30 years in the setting of hemopoietic stem cell transplants (HSCT), with the aim of preventing graft-versus-host disease (GvHD). This is true especially for transplants from alternative donors. In this review, we will be discussing available published and unpublished data on the advantages and disadvantages of using ALG/ATG before or after an allogeneic HSCT. These studies show that ALG/ATG significantly reduce the incidence and severity of acute and chronic GvHD. Unfortunately, they also show that immune deficiency is a more prolonged and infectious complication more frequent in patients receiving ALG/ATG, suggesting the importance of aggressive monitoring of viral and fungal infections. In particular, the emerging problem of Epstein-Barr virus (EBV) infections and EBV-related lymphoproliferative disorders will be discussed, together with the use of pre-emptive therapy with rituximab. I personally believe ALG/ATG has an important role in allogeneic HSCT, especially today with the increasing use of peripheral blood transplants and the consequent high risk of chronic GvHD. ALG/ATG should be used with caution, and the negative consequences must be understood and possibly prevented.
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PMID:Antilymphocyte/thymocyte globulin for graft versus host disease prophylaxis: efficacy and side effects. 1555 41

We studied 228 consecutive stem cell transplant recipients, screened for reactivation of human herpesvirus-6 (HHV-6) in peripheral blood and other specimens as clinically indicated by means of qualitative polymerase chain reaction. Among them, 197 received an allograft and 31 autograft. Ninety-six of 228 patients (42.1%) showed HHV-6 reactivation in peripheral blood and 129 of 228 (56.6%) demonstrated HHV-6 in at least one of the specimens tested. 41.9% of patients were asymptomatic when HHV-6 was identified. Clinical features, noted when HHV-6 was detected, included interstitial or alveolar pneumonia, gastroduodenal and colorectal disease, bone marrow suppression and liver disease. However, based on clinical and histopathological criteria, HHV-6 was considered a causal agent in only a minority of patients, in particular, those suffering from bone marrow suppression (n = 11), gastroduodenitis (five), colitis (three), interstitial/alveolar pneumonia (five), skin rash (one), pericarditis (two) and encephalitis (one). HHV-6 reactivation was significantly associated with the occurrence of graft-versus-host disease [odds ratio (OR) 5.31], Epstein-Barr virus coinfection (OR 8.89) and unrelated donor transplantation (OR 5.67) indicating an increased stage of immunosuppression.
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PMID:Impact of human herpesvirus-6 after haematopoietic stem cell transplantation. 1560 51

Following a human leucocyte antigen (HLA)-identical allogeneic stem cell transplantation (allo-SCT), minor histocompatibility antigens (mHags) play an important role in the induction of graft-versus-leukaemia (GvL) and graft-versus-myeloma (GvM). Many mHags show ubiquitous tissue expression and are associated with GvL and graft-versus-host disease. Here we describe a cytotoxic CD4(+) T lymphocyte line and a cytotoxic, CD4(+) T cell clone (CTC), 3AB11, which recognized a tissue-restricted mHag. This CTC was isolated from a multiple myeloma patient with clinical GvM following an HLA-matched allo-SCT. CTC 3AB11 was activated in a HLA-DP*0401 restricted fashion and the antigen was expressed by 27% of HLA-DP*0401 positive Epstein-Barr virus (EBV)-transformed B-cell lines (EBV-B). Tissue distribution analysis of antigen 3AB11 showed it to be expressed by patient-derived EBV-transformed B cell lines (EBVp), the myeloma plasma cell-line UM9 and monocytes. It was weakly expressed by peripheral blood-derived phytohaemagglutinin-induced T-cell blasts and absent on CD40L stimulated peripheral B (CD40L B) cells and stromal cells. The relatively high prevalence of the HLA class II-restricted 3AB11 antigen, together with its apparent haematopoietic-restricted expression, makes it an antigen of interest for cellular immunotherapy.
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PMID:A class II-restricted cytotoxic T-cell clone recognizes a human minor histocompatibility antigen with a restricted tissue distribution. 1560 52

Cord blood (CB) progenitor cells are increasingly used for transplantation in children because of the lower risk of graft-versus-host disease compared with unrelated bone marrow and comparable rates of disease-free survival. There is concern that CB might carry a higher risk of opportunistic infections. Human herpesviruses (HHV) are common pathogens in transplant recipients. CB donors are routinely tested for the presence of anti-cytomegalovirus (CMV) immunoglobulin M to reduce the risk of collecting CMV-infected CB. To assess the incidence of beta and gamma HHV infection of CB collected under standard procedures, we tested 362 CB samples for the presence of CMV; HHV-6, -7, and -8; and Epstein-Barr virus DNA by polymerase chain reaction. HHV-6 DNA was found in 2 samples, yielding an incidence of 0.55% (95% confidence interval, 0.1%-2%). None of the other viral DNAs was found, resulting in a 95% confidence interval of 0% to 1% for the incidence of CMV, Epstein-Barr virus, HHV-7, and HHV-8. Because the seroprevalence of HHV-8 among the CB donors in this study was only 4%, these findings cannot be extended to HHV-8-endemic areas. Our data show that screening prospective CB donors with anti-CMV immunoglobulin M practically eliminates the risk of CB CMV transmission, but HHV-6 warrants CB testing by polymerase chain reaction.
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PMID:Risk of transmission of herpesviruses through cord blood transplantation. 1562 42


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