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)

Viral infection is commonly observed after bone-marrow transplantation. We isolated adenovirus from 51 of 1051 patients undergoing marrow transplantation between 1976 and 1982. Of the 46 isolates available for typing, 13 (27.7 per cent) were of the closely related species 11, 34, or 35 (subgenus B). All 13 of the patients with these species had positive urine cultures. The species have previously been associated with the acquired immunodeficiency syndrome or with renal transplantation but are not commonly found in community surveys. Invasive infection was confirmed by biopsy or autopsy in 10 of 51 patients. Seven of the 10 had virus isolated from lung, and 4 died from pneumonia attributed to adenovirus. Two of the five patients with renal isolates had evidence of virally induced renal impairment, and both patients with liver isolates had adenovirus hepatitis. There was no common source that accounted for these adenovirus infections, and the most likely source of infection appeared to be endogenous viral reactivation. The only identifiable risk factor for the development of infection and for severe disease was the presence of moderate to severe graft versus host disease.
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PMID:Adenovirus infections in patients undergoing bone-marrow transplantation. 298 98

Certain marrow transplant protocols can now result in a 50-70% long disease-free survival and low relapse rates in acute leukemia (AL) in CR1, CR2, or CML following cytoreduction and HLA-identical marrow infusion. Two-thirds of deaths are due to acute and chronic graft-versus-host disease (GVHD) or viral infection. The other deaths are due to toxicities of the cytoreductive treatment. Prevention of GVHD has been tried by treatment after the transplant or treating the marrow (lymphocyte depletion). Cyclosporine (CsA) or CsA plus methotrexate has reduced acute GVHD but not chronic GVHD. Marrow has been treated with monoclonal antibodies and lectins or elutriated to decrease numbers of T lymphocytes. Some studies have been effective, but the majority have shown an increased number of rejections or leukemic relapses. Apart from teratogenic effects, thalidomide has minimal toxicity. It effectively prevents and treats acute and chronic GVHD in rodent models. Clinical trials will soon begin. Mismatched related or matched unrelated donors have been employed in the clinic with limited success. Alternatively, autologous transplantation in acute leukemia has shown promising results. Possible solutions to remaining problems and strategies will be discussed.
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PMID:Problems and strategies for bone marrow transplantation in acute leukemia and chronic myelogenous leukemia. 305 40

Gastrointestinal inflammation after allogeneic bone marrow transplantation may be due to acute graft-versus-host disease (GVHD) and/or superinfection with opportunistic organisms. Twenty-eight patients with barium studies suggesting gastrointestinal inflammation after bone marrow transplantation and either acute GVHD, viral infection, or both were studied to characterize the radiographic appearances of each disease and to determine whether acute GVHD could be distinguished from viral superinfection on the basis of radiographic findings. Thirteen patients had minimal or no acute GVHD, with viral infection proved in eight and strongly suspected in four others; the remaining patient was thought to have nonspecific inflammatory bowel disease. Five patients had pure acute GVHD, and 10 patients had viral enteritis superimposed on acute GVHD. Radiographic abnormalities were found in the gastrointestinal tract in both acute GVHD and viral infection and were more extensive than previously reported. Findings were similar in both entities, although gastric abnormalities were not seen in pure acute GVHD but only in viral infection, either alone or together with acute GVHD. Prolonged small bowel barium coating occurred in both viral infection and acute GVHD. Fold thickening evolved into fold effacement with a shaggy contour in two patients with viral infection. Colonic findings in all groups mimicked ulcerative colitis. Our data indicate that differentiation between acute GVHD and viral enteritis is not possible on the basis of radiographic findings alone. Both entities should be considered when gastrointestinal inflammation occurs after bone marrow transplantation.
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PMID:Gastrointestinal inflammation after bone marrow transplantation: graft-versus-host disease or opportunistic infection? 327 85

Haemopoietic reconstitution was evaluated in 44 patients given HLA compatible sibling bone marrow transplants. The mean peripheral blood haemoglobin, neutrophil and platelet counts were markedly reduced early post-graft but returned to normal by 26 weeks post transplant. Bone marrow multipotent (CFU-Mix), erythroid (BFU-E) and myeloid (CFU-GM) progenitor cell reconstitution were also assessed at regular intervals up to 2 years post-graft. The mean value of CFU-GM increased gradually and attained a normal value by 52 weeks. The BFU-E value did not reach a normal value until after 52 weeks post-graft. However, CFU-Mix growth appeared to be impaired even up to 2 years post-transplant. The occurrence of graft versus host disease at 3 months post-transplant was associated with significantly lower mean numbers of platelets, marrow CFU-GM, BFU-E and CFU-Mix. Post-transplant patients who were on methotrexate therapy were also shown to have lower marrow CFU-GM and neutrophil values compared to those patients who received cyclosporin post-transplant. This study demonstrated that although peripheral blood counts were normal after 26 weeks post-graft, marrow stem cell reserve in these patients was reduced. This might in part explain the documented increase in risk of severe infections or thrombocytopenia in some of these patients, particularly during viral infection, graft-versus-host disease or immunosuppressive treatment.
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PMID:Haemopoietic reconstitution after allogeneic bone marrow transplantation in man: recovery of haemopoietic progenitors (CFU-Mix, BFU-E and CFU-GM). 354 78

The morphologic changes in the livers of autopsy specimens from recipients of 62 allogeneic bone marrow transplants were reviewed and characterized in specimens from patients who had had apparent drug toxicity, graft-versus-host disease (GVHD), and disseminated cytomegalovirus (CMV) infection. Two conditioning protocols were associated with significant hepatic toxicity. Two of 3 recipients on whom autopsies were performed who had been prepared with high doses of carmustine, cyclophosphamide, and total body irradiation had undergone acute hepatic failure and submassive necrosis with periportal sparing. Seven of 9 patients prepared with busulfan (16 or 20 mg/kg) and cyclophosphamide had moderate to marked centrilobular sinusoidal fibrosis and associated hepatocellular atrophy and necrosis. Twenty of the patients had acute cutaneous GVHD with associated hepatic dysfunction, including 8 with disseminated CMV infection. Of the 12 patients without concomitant CMV infection, 5 had an early onset of GVHD and had predominantly periportal and focal midzonal hepatocellular necrosis, and 7 had acute GVHD with later onset with predominantly bile duct injury. Fifteen patients had evidence of disseminated CMV infection. Whereas CMV infection alone was associated with both hepatocellular and bile duct injury, detectable virus infection was not a requirement for hepatocellular or bile duct injury associated with GVHD.
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PMID:Pathology of the liver with bone marrow transplantation. Effects of busulfan, carmustine, acute graft-versus-host disease, and cytomegalovirus infection. 624 4

Various T cell subsets were characterized by double immunofluorescent staining using monoclonal antibodies (MoAb) in blood, bone marrow (BM) and tissues of 29 patients after allogeneic BM transplantation (BMT). In an attempt to prevent graft versus host disease (GvHD), 15 patients received cyclosporin A (Cy A). In the remaining 14 patients the BM was pre-incubated with a MoAb, OKT3. The regeneration of T4+ subset was delayed and the level of T8+ cells was abnormally high even 1 year after engraftment. This did not have any predictive value for the appearance of complications such as GvHD or severe viral infections. The number of T8+ cells was lower in the group of patients who received Cy A than in the OKT3 group (0.7 +/- 0.2 vs 1.5 +/- 0.3 X 10(9)/1 at day 90). In contrast to normal individuals, the T4/T8 ratio in both blood and regenerating BM of BMT patients was less than 1. A sizeable subset of circulating T cells expressed the phenotype T8+, T10+, HNK-1+, DR+. Circulating cells of this phenotype were transiently very high (up to 50%) in patients with active GvHD or suffering from severe viral infection. This subpopulation of lymphocytes was not found in the epidermal infiltrate that accompanied GvHD where the predominant phenotype was T8+, T1-, T10-, HNK-1-, DR-. We conclude therefore that after BMT the number and phenotype of circulating T cells reflects the T cell distribution seen in the regenerating BM.
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PMID:T cell regeneration after allogeneic bone marrow transplantation. 635 7

In previous reports we demonstrated that increased amounts of the pyrazinopyrimidine compound neopterin are released in the context of T lymphocyte activation. The aim of this investigation was twofold: (1) to define the contribution of hemopoetic cells to neopterin excretion, and (2) to search for the clinical utility of this biochemical marker in the monitoring of such patients. Thirteen patients were grafted with allogeneic, 1 with syngeneic, and 2 with autologous marrow. Urinary neopterin excretion was measured daily by means of high-performance liquid chromatography from the time before transplantation until the patients' discharge from the isolation unit. In all patients bone marrow aplasia was associated with depressed, and engraftment with increased, neopterin values. Rising neopterin levels invariably preceded the cytological definition of "take," on the average by seven days. After hematological reconstitution, neopterin excretion continuously declined in all 5 patients lacking infectious complications and/o-graft-versus-host disease (GVHD). A transitory increase of urinary neopterin followed by normalization was observed in 5 further patients. At the time of increased neopterin excretion, 4 experienced either herpetic infection or GVHD, both of which resolved promptly under the appropriate treatment. Neopterin values remained elevated after engraftment in 6 patients who suffered from persistent GVHD. Results of this pilot study suggest that (1) bone marrow derived cells are crucially involved in production of neopterin in vivo and (2) evaluation of neopterin excretion patterns after hemopoietic reconstitution enables one to discriminate between patients with and without an increased risk of developing GVHD or viral disease.
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PMID:Neopterin as a new biochemical marker in the clinical monitoring of bone marrow transplant recipients. 638 72

Bone marrow transplantation offers two potential therapeutic advantages over more conventional therapy of leukemia. It allows more intensive treatment to be given without regard to marrow toxicity and allows in the case of allogeneic marrow an additional immunotherapeutic effect through graft-versus-host disease (GVHD). Initially, allogeneic transplants in HLA matched sibling donors were only employed in end-stage patients. Although there were encouraging results in terms of long-term therapeutic effects, the overall mortality was prohibitive. Subsequently, patients were transplanted in remission with a marked improvement in overall survival in both acute lymphocytic leukemia and acute non-lymphocytic leukemia. The major obstacles to further improvement in the therapeutic effects of this procedure have been identified (i.e., GVHD, viral infection, and relapse in ALL) and are subject to intensive investigations that already show encouraging results. Syngeneic marrow transplantation is limited for obvious reasons, but early results have shown significant therapeutic effects, in particular, in chronic myelogenous leukemia. These results have encouraged others to use autologous bone marrow. Marrow contamination with unseen tumor cells is being approached by pharmacologic and immunologic techniques designed to "purge" marrow of tumor cells. Animal and initial clinical studies have been encouraging.
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PMID:Bone marrow transplantation: current results in leukemia. 676 16

Natural killer (NK) cell activity toward K562 target cells and antibody-dependent cell-mediated cytotoxicity (ADCC) toward L1210 cell sensitized with anti-L1210 antisera were sequentially tested in peripheral blood lymphocytes (PBLs) from 24 human bone marrow (BM) recipients. Although consistently decreased before the transplant, NK cell activity was restored in all of the patients tested that argues for a bone marrow origin of NK progenitors in humans. In patients without graft-versus-host disease (GVHD), peripheral NK cell activity remained low during the 1st month after the transplant, then rapidly increased and reached normal values usually between days 30 and 50. By contrast, peripheral ADCC appeared earlier restored (since day 13), suggesting that NK and ADCC are two distinct effector mechanisms. When restored, peripheral NK cell activity remained within normal range, except in seven cases with a drastic fall in NK cell values contemporary with a severe viral infection, mainly with cytomegalovirus (CMV). NK cells are thus suggested to play an important role in the control of viral infections in these deeply immunodepressed patients. In patients with acute GVHD, strikingly high NK values were observed early after the transplant, and during the 1st month a strong correlation did exist between high NK values and acute GVHD occurrence. These results suggest that cells involved in GVHD mechanism are able to exert NK cell activity at some stages of their maturation. The assessment of NK cell activity could be an attractive routine procedure for monitoring the prophylaxis of GVHD in human BM recipients.
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PMID:Natural killer cell activity in human bone marrow recipients: early reappearance of peripheral natural killer activity in graft-versus-host disease. 701 2

Patients who receive bone marrow transplants from unrelated donors have a high incidence of graft-versus-host disease (GVHD). If the donor marrow is first T cell-depleted, the everity of GVHD declines but the risk of rejection rises. In an attempt to prevent both graft rejection and GVHD, we included an anti-T cell antibody-toxin conjugate (CD-5-Ricin; XomaZyme H65) in the transplant conditioning regimen. After receiving a partially T cell-depleted marrow, patients then received a second course of immunotoxin as additional GVHD prophylaxis. Eight recipients of unrelated donor marrow transplants were studied. All engrafted (ANC > 500 x 10(6)/l by day 15, range 13-20 days). One patient had grade II skin GVHD and one developed grade IV disease but the other six patients had no acute GVHD. However, there was high morbidity and mortality from virus infections associated with a sluggish return of CD4 and CD8 T cells into the normal range. Four patients died from virus disease (CMV, n = 2; EBV, n = 1; adenovirus, n = 1) and the remaining patients had frequent documented viral illnesses during the first year. We conclude that improvement in the outcome of unrelated donor marrow transplantation will require strategies which prevent rejection and GVHD coupled with attempts to accelerate immune reconstitution.
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PMID:XomaZyme-CD5 immunotoxin in conjunction with partial T cell depletion for prevention of graft rejection and graft-versus-host disease after bone marrow transplantation from matched unrelated donors. 751 37


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