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 have evaluated long-term serial changes in the immunological state from soon after allogeneic bone marrow transplantation (BMT) In 44, mainly leukemia patients with respect to changes in lymphocyte surface markers. Absolute numbers of cluster designation (CD)2+, CD20+ and human lymphocyte antigen-DR+ (HLA-DR+) cells recovered to within their normal ranges three months, one year and two years, respectively, after BMT. The reversal of the CD4+: CD8+ ratio persisted for five years or more but returned to normal after six years. CD57+CD16- cells were markedly increased from three mo up to a maximum of five years after transplantation; they were increased between three and six months after transplantation irrespective of graft-versus-host disease (GVHD), but changes after one year or more differed among patients without GVHD, with acute GVHD, with acute and chronic GVHD or with chronic GVHD. Absolute numbers of CD57+CD16- cells tended gradually to return to normal after one year or more in the group without GVHD but only after six years in patients in the other three GVHD groups.
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PMID:Marked increase of CD57+CD16- cells in long-term survivors of graft-versus-host disease after allogeneic bone marrow transplantation. 135 73

The ability of alloimmune spleen cells expanded in mixed leukocyte culture (MLC) and cloned cytotoxic T lymphocytes (CTL) to kill H-2-compatible leukemia in vivo was evaluated. In comparison with fresh alloimmune spleen cells, MLC-expanded cells had a significantly higher frequency of CTL reactive against leukemia targets in vitro. However, the reactivity of MLC-expanded cells against first-passage spontaneous AKR (H-2k) leukemia in vivo was significantly less than when an equivalent number of fresh alloimmune spleen cells was injected. Comparable antileukemia reactivity was observed in vivo only when the inoculum of MLC-expanded cells was 2-3-fold higher than that of fresh spleen cells. This relative ineffectiveness was attributed to the altered migration pattern of cultured cells in vivo. IL-2-dependent cloned CTL, specific for a normal lymphocyte antigen (Qa-1b) also present on leukemia cells, were derived from MLC-expanded cultures and tested in vivo. For cloned CTL, as with MLC-expanded cells, eradication of AKR leukemia in vivo was associated with the tissue distribution pattern of the injected effector cells. That is, an effective antileukemia reaction was achieved only in tissues in which effector and target proximity was maintained. Qa-1b-specific cloned CTL did not interfere with engraftment of autologous or allogeneic bone marrow in lethally irradiated host mice, nor did they cause any clinically evident graft-versus-host disease. These findings suggest that cloned CTL specific for a normal cell surface antigen with limited host tissue distribution, but present on tumor cells, could be used for adoptive immunotherapy, provided CTL and tumor cell proximity can be attained.
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PMID:Reactivity of in-vitro-expanded alloimmune cytotoxic T lymphocytes and Qa-1-specific cytotoxic T lymphocytes against AKR leukemia in vivo. 241 69

Twenty-one patients with chronic granulocytic leukaemia underwent marrow transplantation. The donors were human-lymphocyte antigen-identical siblings in 19 cases. In the remaining 2 cases the donor was a parent in one and an identical twin in the other. The preparatory regimen included cyclophosphamide and 8.6 Gy total body irradiation given at either a dose of 0.1 Gy/min or 0.04 Gy/min. Five patients were in the accelerated phase of the disease, one was in remission following blast crisis, and the rest were all in the chronic phase. After chemotherapy and irradiation, all patients received bone marrow transplants. To date, nine patients are still alive, with a median survival of 64 days (range 28-683 days). One patient continued to have leukaemic cells and in another, the leukaemia recurred 18 months following transplantation. Interstitial pneumonitis was the cause of death of eight patients (38%). Graft-versus-host disease occurred in ten patients (47%).
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PMID:Bone marrow transplantation for chronic granulocytic leukaemia. 389 94

This article examines the diversity and biologic role of human lymphocyte antigen (HLA) genes as related to marrow transplantation for chronic myelogenous leukemia (CML). A better understanding of the nature and function of HLA variation is necessary as unrelated marrow transplantation evolves into a safe and effective treatment for CML. HLA matching is an important aspect of donor selection criteria and has a role in engraftment as well as the development of graft-versus-host disease and tolerance after transplant.
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PMID:Effect of HLA matching on outcome of related and unrelated donor transplantation therapy for chronic myelogenous leukemia. 952 28

We encountered 2 patients with pneumococcal arthritis following bone marrow transplantation (BMT). Both patients received grafts from unrelated human lymphocyte antigen (HLA)-matched donors and had suffered from chronic graft-versus-host disease (GVHD). One, a 10-year-old boy, suffered from Epstein-Barr virus-related lymphoproliferative disease (EB-LPD) and received oral 6-mercaptopurine and methotrexate to manage lymphadenopathy. Twenty-four months after BMT and 7 months after the onset of EB-LPD, pneumococcal arthritis occurred in both knee joints. The other patient, a 10-year-old girl, received multiagent immunosuppressive therapy for her chronic GVHD. At 51 months following BMT, pneumococcal arthritis occurred in her left knee joint. Chronic GVHD of the skin delayed the recovery from the arthritis in both patients. This complication is quite rare but can be very serious, in regard to the patient's performance status following BMT. Although vaccination against pneumococcus or preventive antibiotics should be administered to high-risk patients, early diagnosis and treatment may be the best strategy for pneumococcal arthritis.
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PMID:Pneumococcal arthritis affects performance status in patients with chronic GVHD of the skin following allogeneic bone marrow transplantation. 1153 Aug 13

Acute graft-versus-host disease (GVHD) and chronic GVHD remain the major barriers to successful haematopoietic cell transplantation. The induction of GVHD may be divided into three phases: recipient conditioning, donor T cell activation and effector cells mediating GVHD. This review examines GVHD prevention and treatment using this conceptual model as framework. The various pharmacological agents discussed impact on different phases of the GVHD cascade. For example, keratinocyte growth factor and IL-11 are cytokines that may be useful in disrupting Phase I of the GVHD cascade by blocking gastrointestinal tract damage and lowering serum levels of lipopolysaccharide and TNF-alpha. Cyclosporin, FK506 and sirolimus are some of the main agents that disrupt Phase II (donor T cell activation). Mycophenolate mofetil likely acts on this phase as well. Other novel drugs that affect Phase II are tolerance-induction agents such as cytotoxic T lymphocyte antigen (CTLA)-4 Ig and anti-CD40 ligand, and preliminary results using CTLA-4 Ig in GVHD prevention are encouraging. Two exciting agents that appear to affect only activated lymphocytes are ABX-CBL and visilizumab. Examples of agents that disrupt Phase III are the IL-2 receptor antagonist daclizumab and the anti-TNF-alpha monoclonal antibody infliximab. These anticytokine antibodies have shown promising results in early studies. The most effective approach to GVHD prevention will likely be a combination regimen where the three phases of the GVHD cascade are disrupted. Once GVHD has occurred, all three phases of the cascade are activated. Developments of combination therapy for treatment of both acute and chronic GVHD will likely yield better results than monotherapy. The numerous new treatment modalities presented should improve the outlook for acute and chronic GVHD.
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PMID:Novel therapeutics for the treatment of graft-versus-host disease. 1222 48

Acute graft-versus-host disease (GVHD) is a primary T-cell-mediated complication of allogeneic hematopoietic stem cell transplantation (HSCT), occurring when donor-derived T cells are stimulated by host antigen-presenting cells (APCs), enhanced by proinflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha. Recent data indicate that besides differences in major histocompatibility and minor histocompatibility antigens, cytokine gene polymorphisms have a predictive value for the complication of GVHD. Patients with a high anti-inflammatory IL-10 production have been demonstrated to be protected from GVHD while patients with high TNF-alpha serum levels were more at risk for GVHD. Pharmacological immunosuppression for GVHD prophylaxis and therapy, including unspecific approaches with corticosteroids or methotrexate (MTX), as well as more specific therapy with cyclosporin A (CsA), tacrolimus (FK506), sirolimus, mycophenolate mofetil (MMF), antithymocyte globulin (ATG), and monoclonal antibodies (MAbs) directed against CD3, CD25, CD52, cytotoxic T-lymphocyte antigen (CTLA)-4, CD40 ligand, or TNF-alpha, have been proven to be effective. Recent data on novel techniques to selectively deplete alloreactive T cells by removal, destruction, or anergy induction while preserving leukemia-specific T-cell clones suggest a clinical benefit from these approaches. Gene-modified T cells that can selectively be depleted and CD4(+)CD25(+) regulatory T cells are under investigation for their ability to modulate alloreactivity after HSCT. With a better understanding of the immunopathogenesis of acute GVHD and the technical improvement of recently described therapeutic approaches, such as removal of naive T cells, selection of Th2 cells, suicide gene transduced T cells, and adoptive transfer of regulatory T cells, the use of alloreactivity as a treatment modality may be expanded to nonhematological disease entities such as solid tumors or autoimmune disorders.
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PMID:Immunopathogenesis of acute graft-versus-host disease: implications for novel preventive and therapeutic strategies. 1544 32

Inducible costimulator (ICOS), a CD28/cytotoxic T lymphocyte antigen 4 (CTLA-4) family member, is expressed on activated T cells. ICOS ligand, a B7 family member, is constitutively expressed on B cells, macrophages, and dendritic cells and is up-regulated on antigen-presenting cells (APCs) and some nonlymphoid tissues by tumor necrosis factor alpha (TNFalpha) or lipopolysaccharide (LPS). Thus, ICOS: ICOS ligand (ICOSL) blockade could reduce alloreactive T cell-APC interactions responsible for graft-versus-host disease (GVHD) and bone marrow (BM) graft rejection. ICOS blockade, achieved with ICOS-/- mice or anti-ICOS monoclonal antibody (mAb) administration, resulted in significant inhibition of GVHD in multiple strain combinations whether mediated by CD4+ and/or CD8+ T cells, alloantigen-specific T-cell receptor (TCR) transgenic (Tg) T cells, or CD28-, T helper 1 (Th1)-, or Th2-deficient T cells. Anti-ICOS significantly delayed GVHD mortality even when mAb infusions were delayed until day 5 after transplantation. ICOS blockade reduced the number of alloantigen-specific effector cells but did not prevent their activation. Imaging of green fluorescent protein-positive (GFP+) effectors indicated that ICOS blockade inhibited expansion of GVHD-causing effector T cells in secondary lymphoid and GVHD target organs. Engraftment rates were significantly higher in ICOS-/- versus wild-type (WT) mice receiving allogeneic BM, and ICOS blockade significantly inhibited expansion of host antidonor alloantigen-specific BM graft-rejecting T cells. These data suggest that the ICOS pathway may be a beneficial therapeutic target for GVHD inhibition, GVHD therapy, and BM graft promotion.
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PMID:Targeting of inducible costimulator (ICOS) expressed on alloreactive T cells down-regulates graft-versus-host disease (GVHD) and facilitates engraftment of allogeneic bone marrow (BM). 1561 67

The clinical and histological presentation of inflammatory disease in the skin is exceedingly heterogeneous. Nonetheless, most inflammatory dermatoses can be classified according to five stereotypical tissue-reaction patterns: the spongiotic, the lichenoid, the psoriasiform, the vesiculo-bullous and the vasculopathic. By means of potent antigen-presenting cells, cytokine and chemokine cascades and a skin-specific cutaneous lymphocyte antigen (CLA)-positive lymphocyte population, the skin is able to respond very efficiently to pathogens that threaten the individual. Inflammatory skin diseases follow the rules and routes of the physiological reaction to inflammation but however for various reasons the immune response may be inadequate, enhanced or chronic. In allergic contact dermatitis, which is a prototype of the spongiotic reaction pattern, the inflammation is directed against an otherwise harmless antigen, for which the body is sensibilized. Lichenoid dermatitis (like erythema multiforme, graft versus host disease or lupus erythematodes) is based on a primary cytotoxic reaction against the basal epithelial cell, due to alterations in its antigenic make-up or due to an altered immune response. In psoriasis, an example of psoriasiform dermatitis, the interaction between inflammatory cells, antigen presenting cells and epithelial cells is disturbed.
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PMID:[The immune system of the skin and stereotyped reaction patterns in inflammatory skin diseases]. 1722 34

We present a case of concurrent diagnosis of acute myeloid leukemia (AML) with multiple myeloma with complex karyotype, which was successfully treated with allogeneic stem cell transplantation. A 51-year-old man with no past medical history presented with fatigue and anemia with blasts on peripheral smear. Bone marrow biopsy confirmed the simultaneous diagnosis of myeloma and AML. The patient received bortezomib and the myeloma responded well, but induction chemotherapy for the AML failed twice. He underwent an allogeneic stem cell transplant from his human lymphocyte antigen (HLA)-matched sibling, and is now disease-free approximately one year since the transplant. He has mild graft-versus-host disease (GVHD). To our knowledge, this is the first case of a patient with simultaneous AML and multiple myeloma who has undergone successful treatment with allogeneic stem cell transplantation.
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PMID:Simultaneous acute myeloid leukemia and multiple myeloma successfully treated with allogeneic stem cell transplantation. 2103 23


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