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)

Pulmonary function was measured before and at intervals after treatment in 44 patients who received a bone marrow transplant for chronic myeloid leukaemia in the chronic phase. All patients were treated with cytotoxic drugs, total body irradiation, and post-graft immunosuppression. Thirty four patients surviving for 12 months were followed at three monthly intervals and 16 patients for 24 months. Fifteen patients received unmanipulated donor marrow cells and 29 patients received donor marrow cells depleted of lymphocytes ex vivo with the monoclonal antibody Campath-1. The 21 patients treated early in this study received 10 Gy of total body irradiation whereas the 23 patients treated more recently, who were all T lymphocyte depleted, received 12 Gy. Pretransplant lung function for the group was normal and was similar in survivors (n = 34) and nonsurvivors (n = 10), and in smokers (n = 8) and non-smokers (n = 36). (Carbon monoxide transfer factor--TLCO) was under 75% of predicted normal in nine patients before transplantation. TLCO, carbon monoxide transfer coefficient (KCO), FEV1, and vital capacity (VC) values were lower 6 and 12 months after bone marrow transplant than initially. The greatest decline was in TLCO, from an initial value of 89% to 66% at 6 and 70% at 12 months. The 16 longer term survivors showed significant recovery of function between 6 and 24 months after bone marrow transplant for TLCO, KCO, and VC, the increase ranging from 6.3% to 7.3% predicted. Airflow obstruction (FEV1/VC ratio less than 70%) developed in one patient. The major factors associated with deterioration in pulmonary function at 6 and 12 months after transplantation in the 34 survivors (stepwise multiple regression analysis) were (a) transplantation with T cell depleted donor marrow (p less than 0.005) and higher total body irradiation dose (p less than 0.02) with a fall in KCO and an increase in the FEV1/VC ratio; (b) chronic graft versus host disease with a fall in VC (p less than 0.01); and less fall in KCO (p less than 0.01); and (c) acute graft versus host disease with a fall in FEV1 (p less than 0.01). It is considered that most patients who survive the short term risks of bone marrow transplant have only minor long term impairment of pulmonary function.
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PMID:Pulmonary function after bone marrow transplantation for chronic myeloid leukaemia. 304 53

After conventional bone marrow transplantation serum IgG, IgM and IgA levels fall from pre-transplant levels and may not return to normal for 3-12 months. In contrast IgE may rise to supranormal levels, an event that may be associated with graft-versus-host disease. We have investigated the recovery of immunoglobulin isotypes in the recipients of allogeneic marrows depleted of T-cells to prevent graft-versus-host disease. We find that pre-transplant IgG, IgM and IgA levels are maintained throughout the post-transplant period but that there is a short-lived rise in IgE about 3 weeks after transplantation: this rise occurs in the absence of clinically detectable graft-versus-host disease. We conclude that specific T-cell depletion does not impair and may actually enhance the functional recovery of B cells after allogeneic BMT.
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PMID:Recovery of immunoglobulin isotypes following T-cell depleted allogeneic bone marrow transplantation. 353 Mar 13

After haematopoietic stem cell transplantation, reconstitution of bone marrow consists of two distinct phenomena, numerical recovery of bone marrow cellular elements on the one hand and functional recovery of cellular interactions on the other. Immune reactivity during the first month postgrafting is extremely low. Cytotoxic and phagocytic functions usually recover by day 100, while more specialized and cooperative functions of T and B cells remain impaired up to one year or more postgrafting. Regeneration of total CD4+ T cell number in adult (and especially in elderly) transplant recipients is severely limited and occurs largely by peripheral expansion of mature CD4+ T cells. While restoration of total CD8+ T cell number is commonly seen in adults, potentially important alterations in the subset composition of CD8+ populations remain. Contracted T cell repertoires for CD4+ and CD8+ T cells are consistently found in adults after T cell regeneration. This suggests that thymic function is frequently limiting in adults and that thymic-independent pathways are insufficient for restoring host immunocompetence. Although there are similarities in immune reconstitution after alllo- and autologous haematopoietic stem cell transplantations, allogeneic transplantation involves graft versus host disease and the use of immunosuppressive therapy to control it, both of which further interfere in the early developmental stages of immune reconstitution.
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PMID:[Regeneration of the immune system after bone marrow transplantation]. 1120 6

Reconstitution of cellular immunity by 3 months after hematopoietic stem cell transplantation (HSCT) is a critical determinant of the long-term success of the transplantation. We analyzed the factors affecting recovery of cytomegalovirus (CMV)-specific CD4+ and CD8+ function at 3 months after HSCT by univariate and multivariable analyses including source of stem cells (bone marrow vs peripheral blood stem cells [PBSCs]), age, sex, graft-versus-host disease (GVHD), steroid use, conditioning regimens, ganciclovir use, HLA matching, circulating CMV antigenemia, absolute CD4+ and CD8+ counts, and donor CMV serology. High-dose steroids and CD4+ count less than 100 x 10(9)/L were significant predictors of impaired CD4+ functional recovery in the multivariable analysis. High-dose steroids, bone marrow as a source of stem cells, and CD8+ count less than 50 x 10(9)/L were associated with impaired CD8+ function in the multivariable analysis. Steroids were found to impair both CD4+ and CD8+ function in a dose-dependent manner. In the absence of high-dose steroids, low-level subclinical CMV antigenemia was found to stimulate both CD4+ and CD8+ functional recovery in recipients of ganciclovir prophylaxis. There was no difference in immune reconstitution between those who received prophylactic ganciclovir versus antigenemia-guided pre-emptive therapy. Thus, absolute CD4+ and CD8+ counts less than 100 x 10(9)/L and 50 x 10(9)/L, respectively; bone marrow as the source of stem cells; and high-dose steroid use all predict delayed recovery of functional T-cell immunity at 3 months after transplantation. Subclinical CMV reactivation while on ganciclovir appears to be a potent stimulator of T-cell function. These findings have implications for vaccination and adoptive-immunotherapy strategies in this population.
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PMID:Immune reconstitution to cytomegalovirus after allogeneic hematopoietic stem cell transplantation: impact of host factors, drug therapy, and subclinical reactivation. 1284

Based on the results achieved in single human hand transplantations, we decided to perform the first double hand transplantation with a conventional immunosuppressive protocol in a patient with a high potential for functional recovery. Two years after transplantation the efficacy and the safety of this immunosuppressive protocol are evaluated. The recipient was a 33-yr-old man suffering from a traumatic amputation of both hands in 1996. Five HLA-A, -B, and -DR mismatches were present with the donor; T and B cell cross-match was negative. Immunosuppressive protocol included tacrolimus, prednisone, mycophenolate mofetil and, for induction, antithymocyte globulins and then anti CD25 monoclonal antibody. Reconstitution of lymphocyte populations proceeded normally. Neither anti-HLA antibodies nor chimerism in peripheral blood were detected. Two episodes of acute rejection characterized by maculopapular lesions occurred on days 53 and 82 after transplantation. Skin biopsies revealed a dermal lymphocytic infiltrate. Both episodes were completely and rapidly reversed by topical clobetasol and increased systemic corticosteroid therapy. The only side-effects related to treatment were reversible serum sickness and hyperglycemia. No infectious complications and malignancies occurred. No signs of graft-versus-host disease have been detected. This case of double hand transplantation shows that conventional immunosuppression is effective and safe to ensure survival and functional recovery of the grafted limb.
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PMID:First human double hand transplantation: efficacy of a conventional immunosuppressive protocol. 1470 30

Graft-versus-host disease is a major complication for bone marrow transplant recipients and is often a cause of late mortality. It can affect any tissue, and involvement of the lungs--target organs of particular importance--can lead to chronic respiratory failure due to bronchiolitis obliterans. We report the case of a lung transplant in a woman who developed bronchiolitis obliterans after receiving a marrow transplant to treat bone marrow aplasia. Three years later, clinical course was satisfactory, with full functional recovery.
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PMID:[A lung transplant in a woman with bronchiolitis obliterans following an allogenic bone marrow transplant]. 1654 56

In a murine model of systemic lupus erythematosus (SLE)-like chronic graft-versus-host disease (cGVHD), donor CD8+ T cells rapidly fall into anergy to host cells, while donor CD4+ T cells hyperactivate B cells and break B-cell tolerance to self-Ags in the recipient mouse. The functional recovery of donor CD8+ T cells can result in the conversion of cGVHD to acute GVHD (aGVHD), indicating that donor CD8+ T-cell anergy is a restriction factor in the development of cGVHD. In this report, we present evidence that donor CD4+CD25+ regulatory T cells (Treg cells) are critical in maintaining the donor CD8+ T-cell anergy and thus suppressing the development of aGVHD in mice that are naturally prone to cGVHD. Our results provide a novel insight into the role of Treg cells in determining cGVHD versus aGVHD.
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PMID:Maintenance of CD8+ T-cell anergy by CD4+CD25+ regulatory T cells in chronic graft-versus-host disease. 1707 65

Infusing natural killer (NK) cells following transplantation may allow less infections and relapse with little risk of acute graft-versus-host disease (aGVHD). We delivered 51 total NK cell-enriched donor lymphocyte infusions (DLIs) to 30 patients following a 3-6/6 HLA matched T cell-depleted nonmyeloablative allogeneic transplant. The primary endpoint of this study was feasibility and safety. Eight weeks following transplantation, donor NK cell-enriched DLIs were processed using a CD56(+) selecting column with up to 3 fresh infusions allowed. Toxicity, relapse, and survival were monitored. T cell phenotype, NK cell functional recovery, and KIR typing were assessed for association with outcomes. Fourteen matched and 16 mismatched transplanted patients received a total of 51 NK cell-enriched DLIs. Selection resulted in 96% (standard deviation [SD] 8%) purity and 83% (SD 21%) yield in the matched setting and 97% (SD 3%) purity and 77% (SD 24%) yield in the mismatched setting. The median number of CD3(-) CD56(+) NK cells infused was 10.6 (SD 7.91) x 10(6) cells/kg and 9.21 (SD 5.6) x 10(6) cells/kg, respectively. The median number of contaminating CD3(+)CD56(-) T cells infused was .53 (1.1) x 10(6) and .27 (.78) x 10(6) in the matched and mismatched setting, respectively. Only 1 patient each in the matched (n = 14) or mismatched (n = 16) setting experienced severe aGVHD with little other toxicity attributable to the infusions. Long-term responders with multiple NK cell-enriched infusions and improved T cell phenotypic recovery had improved duration of responses (p = .0045) and overall survival (OS) (P = .0058). A 1-step, high-yield process is feasible, and results in high doses of NK cells infused with little toxicity. NK cell-enriched DLIs result in improved immune recovery and outcomes for some. Future studies must assess whether the improved outcomes are the direct result of the high doses and improved NK cell function or other aspects of immune recovery.
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PMID:Natural killer cell-enriched donor lymphocyte infusions from A 3-6/6 HLA matched family member following nonmyeloablative allogeneic stem cell transplantation. 2018 2

Mesenchymal stem cells/marrow stromal cells (MSCs) present a promising tool for cell therapy, and are currently being tested in US FDA-approved clinical trials for myocardial infarction, stroke, meniscus injury, limb ischemia, graft-versus-host disease and autoimmune disorders. They have been extensively tested and proven effective in preclinical studies for these and many other disorders. There is currently a great deal of interest in the use of MSCs to treat neurodegenerative diseases, in particular for those that are fatal and difficult to treat, such as Huntington's disease and amyotrophic lateral sclerosis. Proposed regenerative approaches to neurological diseases using MSCs include cell therapies in which cells are delivered via intracerebral or intrathecal injection. Upon transplantation into the brain, MSCs promote endogenous neuronal growth, decrease apoptosis, reduce levels of free radicals, encourage synaptic connection from damaged neurons and regulate inflammation, primarily through paracrine actions. MSCs transplanted into the brain have been demonstrated to promote functional recovery by producing trophic factors that induce survival and regeneration of host neurons. Therapies will capitalize on the innate trophic support from MSCs or on augmented growth factor support, such as delivering brain-derived neurotrophic factor or glial-derived neurotrophic factor into the brain to support injured neurons, using genetically engineered MSCs as the delivery vehicles. Clinical trials for MSC injection into the CNS to treat traumatic brain injury and stroke are currently ongoing. The current data in support of applying MSC-based cellular therapies to the treatment of neurodegenerative disorders are discussed.
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PMID:Mesenchymal stem cells for the treatment of neurodegenerative disease. 2108 92

Because of their immunomodulatory and engraftment-promoting properties, mesenchymal stromal cells (MSCs) have been tested in the clinical setting both to facilitate haematopoietic recovery and to treat steroid-resistant acute GVHD. More recently, experimental findings and clinical trials have focused on the ability of MSCs to home to damaged tissue and to produce paracrine factors with anti-inflammatory properties, resulting in functional recovery of the damaged tissue. The mechanisms through which MSCs exert their therapeutic potential rely on some key properties of the cells: the ability to secrete soluble factors capable of stimulating survival and recovery of injured cells; the capacity to home to sites of damage and the ability to blunt exaggerated immune responses. These fundamental properties are being tested within a novel therapeutic field defined as Regenerative Medicine. This review deals with recent research on the anti-inflammatory/reparative properties of MSCs and considers the possible mechanisms of function responsible for these effects. Moreover, current and potential clinical applications of MSC-based treatment strategies in the context of Regenerative Medicine are being discussed. Key issues such as optimal timing of MSC administration, cell dose and schedule of administration, advantages and disadvantages of using autologous or allogeneic cells are still open. Nonetheless, MSCs promise to represent a revolution for many severe or presently untreatable disorders.
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PMID:Mesenchymal stromal cell therapy: a revolution in Regenerative Medicine? 2147 14


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