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)

A microangiopathic syndrome was observed in 3 of 14 (21%) patients receiving cyclosporine and methylprednisolone (CSA-MP) for graft-versus-host disease (GVHD) prophylaxis between January 1991 and June 1992 at our center. The syndrome consisted of neurological abnormalities, arterial hypertension, intravascular hemolysis with red cell fragmentation, and a drop in platelet counts after allogeneic bone marrow transplantation (BMT) for hematological malignancy, and it occurred around day 50 after BMT. Treatment with plasma exchanges against fresh-frozen plasma resulted in a decrease of serum lactate dehydrogenase and an improvement of neurological symptoms. We compared CSA-MP patients retrospectively with patients who had received cyclosporine and methotrexate (CSA-MTX) for GVHD prophylaxis (n = 70) at our institution. All patients in both groups engrafted. Day 100 survival (80% vs. 79%) and transplant-related mortality (16% vs. 14%) were identical in the two groups. CSA-MP patients had significantly more acute GVHD II-IV (57% vs. 17%, P < 0.01). Arterial hypertension (P < 0.01) and neurological symptoms (P < 0.01) were significantly more frequent in the CSA-MP group. The 11 asymptomatic CSA-MP patients had significantly higher lactate dehydrogenase levels (P < 0.01) and lower platelet counts (P < 0.01) at 40, 60, and 100 days after BMT, which suggests the presence of a subclinical form of microangiopathy. Significantly higher plasma levels of von Willebrand factor antigen in CSA-MP patients on day 50 after BMT (P < 0.05) and absence of large von Willebrand factor multimers on gel electrophoresis in 4 of 13 (31%) CSA-MP patients compared with 0 of 14 (0%) CSA-MTX patients (P < 0.01) further suggest profound endothelial damage in patients receiving CSA-MP for GVHD prophylaxis.
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PMID:Microangiopathy following allogeneic marrow transplantation. Association with cyclosporine and methylprednisolone for graft-versus-host disease prophylaxis. 749 99

Endothelial cell activation during allogeneic bone marrow transplantation, mainly in acute graft-versus-host disease (aGvHD) was studied in 23 recipients and 5 controls using anti-von Willebrand factor (vWF) antibody, antibodies to endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), and anti-HLA-DQ antibody, by immunohistological staining of skin. vWF extravasation, ELAM-1 and VCAM-1 expression were present in most recipients with a cutaneous rash which was confirmed as an aGvHD by histological examination (documented aGvHD) (p = 0.005 for vWF extravasation and ELAM-1 expression and p = 0.03 for VCAM-1 expression in comparison with the controls). In recipients with a rash, the cases displaying vWF extravasation and ELAM-1 expression were significantly more numerous in those with a documented aGvHD than in those without histological features of aGvHD (p = 0.01). vWF extravasation and ELAM-1 occurred concomitantly (p < 0.01). This study demonstrates that, during the course of skin aGvHD following bone marrow transplantation, there is transient expression of ELAM-1 and VCAM-1 by endothelial cells and simultaneous vWF extravasation, indicating an intense inflammation with endothelial cell participation.
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PMID:Expression of adhesion molecules in endothelial cells during allogeneic bone marrow transplantation. 751 72

In order to study the relationship between plasma and platelet von Willebrand factor (vWF), we used an experimental model of crossed bone marrow transplantation (BMT) between SLA immunocompatible normal and homozygous von Willebrand (vWD) pigs. A normal pig received bone marrow from a vWD pig and a second pig with vWD was engrafted with marrow from a normal pig. Each recipient, after total irradiation of 10 Grays, received by a central catheter 10(10) monocellular bone marrow cells without immunosuppression. The animals were followed for 50 d and no graft rejection or graft-versus-host disease was observed. After aplasia occurring 3 weeks after BMT, white blood cells and platelets returned to normal. Before transplantation, in the vWD pig, vWFAg and vWF activity were not detected in plasma and in platelet and megakaryocyte alpha-granules. After transplantation with normal marrow, platelet vWFAg and platelet vWF activity wer normal and high molecular weight multimers and numerous tubular structures were present in alpha-granules. Before transplantation, the normal pig had normal plasma and platelet vWFAg-vWF activity, normal multimeric pattern, and the platelet and megakaryocyte alpha-granules displayed many tubular structures, eccentrically located in one of their poles, coinciding with immunogold staining vWFAg. After transplantation with homozygous vWD marrow, platelet and megakaryocyte alpha-granules lacked tubular structures. Alpha-granule immunogold staining for vWF was consistently negative, although plasma vWF was at a normal level. In conclusion, this study shows that, unlike other plasma proteins such as fibrinogen. vWF endocytosis does not occur from plasma to the platelet alpha-granules. Platelet and megakaryocyte vWF solely originates from megakaryocyte endogenous synthesis and is independent of plasma vWF.
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PMID:Absence of incorporation of plasma von Willebrand factor into porcine platelet alpha-granules. 764 7

Changes in hemostatic factors after bone marrow transplantation (BMT), with or without thrombotic complications, have already been described. The endothelium seems to be actively involved in such processes. Over a period of 2 years we evaluated various hemostatic factors, associated or not with endothelial stimulation, in 44 patients with BMT (40 leukemias and 4 aplastic anemias). Factor VIII activity (VIII:C), von Willebrand factor antigen (vWF:Ag), tissue plasminogen activator antigen (tPA), plasminogen activator inhibitor activity (PAI-1), antithrombin III, protein C and protein S were assayed before and 1, 3, 6, 12, 18, and 24 months after BMT. Factor VIII:C, vWF and tPA were found to be significantly increased 1-6 months after BMT, returning to normal later. Patients with acute graft versus host disease, fever or cyclosporin treatment had significantly higher VIII:C, vWF and tPA. The increase in these factors implies lasting stimulation of their release and/or synthesis from endothelial cells that is enhanced by some complications of BMT. The degree and character of these changes could favor activation of thrombotic processes.
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PMID:[Activation of endothelium-dependent hemostatic factors following bone marrow transplantation]. 789 69

To investigate endothelial cell alterations in BMT recipients developing acute graft-versus-host disease (aGVHD) we determined levels of the endothelial cell markers von Willebrand factor (VWF) and thrombomodulin (TM) in 57 patients undergoing BMT. Before conditioning VWF and TM levels did not differ significantly between transplant recipients who later developed no or mild (grade I) aGVHD (group A, allogeneic n = 22, autologous n = 7; VWF 136.0 +/- 44.1%; TM 29.5 +/- 18.0 ng/ml), and those with moderate or severe (grade II or III) aGVHD (group B, n = 28; VWF 142.2 +/- 37.6%; TM 35.2 +/- 20.1 ng/ml). A first significant rise of both VWF and TM level was noted after conditioning (day 0) both in group A (VWF 197.0 +/- 113.3%; P < 0.001; TM 39.3 +/- 23.3 ng/ml; P < 0.01) as well as in group B (VWF 201.7 +/- 53.3%; P < 0.0001; TM 43.5 +/- 23.5 ng/ml; P < 0.05). Subgroup analysis of autografted patients revealed no significant increase after conditioning in these patients. At the time of engraftment and onset of aGVHD (day 21), when VWF and TM levels within the groups were significantly elevated as compared with baseline (day -8) levels, group B patients (62.7 +/- 38.5 ng/ml) had significantly higher (P < 0.01) TM levels than patients of group A (37.4 +/- 19.6 ng/ml). This significant elevation also persisted at the end of the investigational period (day 28; group B: 56.0 +/- 37.6 ng/ml; group A: 38.2 +/- 23.7 ng/ml; P < 0.01). An elevation of endothelial cell markers is found in the course of BMT, particularly after conditioning and at the time of engraftment. This increase is pronounced in patients with aGVHD suggesting not only epithelial cell but also endothelial cell injury during aGVHD.
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PMID:Endothelial cell markers in bone marrow transplant recipients with and without acute graft-versus-host disease. 915 65

We investigated hemostatic parameters in a prospective study of 16 patients who received bone marrow transplants (BMT). We found a significant rise in the levels of fibrinogen, plasmin-alpha2 antiplasmin inhibitor complex, tissue-plasminogen activator.plasminogen activator inhibitor complex (t-PA.PAI), von Willebrand factor antigen, and thrombomodulin on day 14 after transplant compared with values before transplant. Protein C and thrombin-antithrombin III levels did not change significantly. No significant changes in prothrombin time ratio, activated partial thromboplastin time, or protein S were detected. Patients who had grades II-IV graft-versus-host disease (GVHD) (n = 6) showed a significantly higher level of t-PA.PAI on day 14 compared with those with grades 0-I GVHD (n = 10) (P = 0.0062). Three patients with grades II-IV GVHD developed thrombotic microangiopathy (TMA) on days 19, 19 and 62. In these patients, we noted significantly lower levels of fibrinogen (P = 0.0383), and significantly higher levels of t-PA.PAI (P = 0.0008) and thrombomodulin (P = 0.0001) on day 14 compared with those patients who did not develop TMA. These results suggest that prothrombotic states and endothelial damage may be caused by the conditioning regimen and/or acute GVHD during BMT; thrombomodulin values on day 14 post BMT may be useful in surveillance for TMA because of endothelial cell injury.
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PMID:Diagnostic value of hemostatic parameters in bone marrow transplant-associated thrombotic microangiopathy. 957 11

We encountered two patients with uncommon neurological manifestations after allogeneic bone marrow transplantation (BMT), which occurred with rapid elevation of the leukocyte count at engraftment. Both patients then developed severe acute graft-versus-host disease (GVHD). To investigate the pathogenesis, we measured the levels of soluble P-selectin, von Willebrand factor (vWF) and thrombomodulin (TM), which reflect endothelial damage. The P-selectin, vWF and TM levels in the patients with (n=2) and without (n=5) neurotoxicity were, respectively, 168.5+/-52.5 ng/ml vs 27.7+/-3.9 ng/ml, 6.7+/-0.15 FU/ml vs 3.42+/-0.41 FU/ml and 459+/-37% vs 189.4+/-32.4% (mean+/-s.d.). All three parameters were much higher in the patients with neurological complications. These results suggest that neurotoxicity after BMT may be related to endothelial damage.
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PMID:The levels of soluble P-selectin, von Willebrand factor and thrombomodulin in patients with neurological complications after allogeneic bone marrow transplantation. 960 5

Each year in the US, more than 10 000 patients benefit from allogeneic haematopoietic stem cell transplantation (HSCT), a modality that offers an excellent chance of eradicating malignancy but confers a higher risk of treatment-related mortality. An uncommon but devastating consequence of HSCT is transplantation-associated thrombotic microangiopathy (TA-TMA). The incidence of TA-TMA ranges from 0.5% to 76%, with a mortality rate of 60-90% despite treatment. Although there appears to be a consistent treatment approach to idiopathic thrombotic thrombocytopenic purpura (TTP) using plasma exchange, corticosteroids and rituximab, the treatment strategies for TA-TMA are perplexing, in part, because the literature regarding this complex condition does not provide true consensus for incidence, aetiology, diagnostic criteria, classification and optimal therapy. The classic definition of idiopathic TTP includes schistocytes on the peripheral blood smear, thrombocytopenia and increased serum lactate dehydrogenase. Classic idiopathic TTP has been attributed to deficient activity of the metalloproteinase responsible for cleaving ultra-large von Willebrand factor multimers. This protease is a member of the 'a disintegrin and metalloprotease with thrombospondin type 1 motif' family and is subsequently named ADAMTS-13. Severely deficient ADAMTS-13 activity (<5% of normal) is associated with idiopathic TTP in 33-100% of patients. In constrast to the pathophysiology of idiopathic TTP, patients with TA-TMA have >5% ADAMTS-13 serum activity. These data may explain why plasma exchange, a standard treatment modality for idiopathic TTP that restores ADAMTS-13 activity, is not effective in TA-TMA. TA-TMA has a multifactorial aetiology of endothelial damage induced by intensive conditioning therapy, irradiation, immunosuppressants, infection and graft-versus-host disease. Treatment consists of substituting calcineurin inhibitors with an alternative immunosuppressive agent that possesses another mode of action. One candidate may be daclizumab, especially in those with mild to moderate TMA. Rituximab therapy or the addition of defibrotide may also be beneficial. In general, plasma exchange is not recommended.
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PMID:Thrombotic microangiopathy in haematopoietic stem cell transplantation: diagnosis and treatment. 1922 75