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 a single center experience of 222 patients (pts) less than 18 years old transplanted from 1973 to 1987. The median age was 11 years (1-18). The donor was a monozygotic twin (9 pts), an HLA-id sibling (193 pts), an HLA-id, parent (9 pts), a mismatched related donor (9 pts) and a matched unrelated donor (1 pt). Ninety-six pts were transplanted for SAA. Conditioning varied with time but the majority (59 pts) received CY 150 mg/kg and 6 Gy TAI. The long term actuarial survival is 66% with a median follow-up of 3 years. The group who received CY 200 mg/kg and MTX had a 33% long term survival (LTS). GVH was the main complication with 40% acute and 37% chronic GVHD. Chronic GVHD tended to improve with time after 2 to 4 years of evolution. Ninety pts were transplanted for leukemia (35 AML, 45 ALL and 11 CGL), 20 pts were in relapse. Pts in CR had a LTS of 40%, in pts in relapse, it was 12%. The main causes of death were: interstitial pneumonitis (30%), relapse (27%), GVH (15%). Thirty-five pts were transplanted for constitutional disease: Fanconi anemia (FA) (26 pts), Dyskeratosis congenita (2 pts), Blackfan-Diamond erythroblastopenia (2 pts), Glanzmann thrombasthenia (1 pt), osteopetrosis (1 pt) and Gaucher's disease (1 pt). In FA, the LTS is 70% with a CY 20 mg/kg, 5 Gy TAI regimen. In all disease categories, we did not find any influence of donor's sex on GVH and survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pediatric bone marrow transplantation for leukemia and aplastic anemia. Report of 222 cases transplanted in a single center. 267 24

Twenty-one patients with Fanconi's anaemia (FA) were treated by allogeneic bone marrow transplantation (BMT). Two, transplanted before 1980, received high dose cyclophosphamide conditioning and both died. Subsequently 19 patients received conditioning with low dose cyclophosphamide 5 mg/kg x 4 and total body irradiation 200 cGy x 3. Ten of 19 received HLA identical sibling marrow (ID-BMT) and nine marrow from alternative donors (MM-BMT). Marrow was T cell depleted in 9/19 cases. Sustained engraftment was observed in 13 cases (eight ID-BMT, five MM-BMT). Nine patients developed greater than or equal to grade II acute graft-versus-host disease (GVHD) (six ID-BMT, nine MM-BMT). Chronic GVHD occurred in 5/11 evaluable patients. Overall survival of the low dose cyclophosphamide group was 9/19 (47%) at a median follow-up of 1257 days post-BMT (110-1825). Six of 10 (60%) survived after ID-BMT compared with two of nine (22%) after MM-BMT. We conclude that allogeneic BMT using a low dose cyclophosphamide protocol is a satisfactory treatment for FA patients who have a normal HLA identical sibling. The results of MM-BMT have been poor, and must improve before these transplants can be generally recommended for treatment of FA.
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PMID:Bone marrow transplantation for Fanconi's anaemia: the Hammersmith experience 1977-89. 268 8

Chronic graft-versus-host disease (GVHD) is a very heterogeneous entity with variable clinical expression. The pathophysiology involves autoimmune disorders and features of fibrosis. Four patients transplanted for severe aplastic anaemia conditioned with cyclophosphamide and thoraco-abdominal irradiation developed skin scleroderma specifically localized in the irradiation fields. This syndrome was remarkable for its late onset and the absence of factors known to trigger chronic GVHD. It is postulated that irradiation used in this protocol may induce keratinocyte damage and trigger chronic GVHD.
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PMID:Unusual localization of cutaneous chronic graft-versus-host disease in the radiation fields in four cases. 292 34

The cellular immune response to herpesviruses was studied in 46 recipients of marrow grafts (23 autologous, 23 allogeneic). That study was performed in vitro by evaluating the degree of lymphocyte proliferative responses to herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella zoster virus (VZV). No primary infections with any of those viruses were noted after bone marrow transplantation (BMT). The incidence of active infection in seropositive patients was significantly lower after autologous BMT than after allogeneic BMT (HSV, 2/22 vs. 11/22 patients, respectively, P = 0.007; CMV, 4/12 vs. 9/10 patients, respectively, P = 0.02; VZV, 3/23 vs. 11/23 patients, respectively, P = 0.02). After autologous BMT, the restoration of cellular immunity to the three viruses occurred at a clearly faster rate than after allogeneic BMT. That pattern may have contributed to the low incidence of active infections with those viruses after autologous BMT. Recipients of allogeneic marrow from donors with a positive lymphocyte proliferation test to HSV had a significantly increased incidence of active HSV infection post-BMT (8/9 patients) than those who received marrow from donors with a negative test (3/13 patients; P = 0.008). Acute or chronic graft-versus-host disease (GVHD) decreased the cellular immune response to the three herpes viruses, but not significantly. Our program of vaccinations with diphtheria and tetanus toxoids started in the fourth month post BMT. Chronic GVHD patients who were vaccinated had a clearly impaired cellular immune response to both toxoids as compared with those without chronic GVHD.
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PMID:Cellular immunity to vaccinations and herpesvirus infections after bone marrow transplantation. 301 33

This article has outlined the special problems associated with evaluation of bone marrow before and after BMT. Marrow grafting has become a major form of therapy in oncology and hematology whose potential is only beginning to be fully realized. The transplantation of healthy hematopoietic and lymphoid cells has made possible the use of otherwise superlethal doses of radiation and chemotherapy in preparing the patient for engraftment. In the case of tumors, this allows massive doses of tumorocidal therapy prior to rescue with a BMT. In the case of aplastic anemia, it allows massive immunosuppression and ablation of the residual host marrow in preparation for replacement by the healthy donor marrow. The complications of this procedure include the toxicity of chemotherapy and irradiation upon the liver, lung, and gut as well as less serious toxicity to skin and other organs. The double barrier associated with marrow transplantation consists of rejection and GVHD. Marrow graft failure occurs by two distinct mechanisms, graft resistance and graft rejection. The former is marked by a total failure of any evidence of engraftment and the latter by engraftment followed by disappearance of the graft. GVHD is the immunologic attack upon host tissues by donor lymphoid cells (predominantly mature T cells). In the acute phase, it attacks liver, skin, and gut, with the latter producing the most life-threatening syndrome. Chronic GVHD resembles scleroderma. Treatment of GVHD includes the use of prednisone, cyclosporin A, ATG, and monoclonal antilymphoid antibodies. Prevention includes the attempt to remove T cells from the donor marrow with monoclonal antibodies using complement-mediated cytolysis and other approaches such as conjugation of antibodies to ricin and other toxins. GVHD also produces severe immunosuppression in and of itself added to that produced by chemoirradiation therapy. As a result, the marrow transplant recipient is extremely susceptible to infections. During the early period, the patient is granulocytopenic and susceptible to bacterial and fungal infections, which are dealt with by antibiotics and isolation procedures. Later, viral infections become very important, particularly CMV and other herpes viruses. The relative success in dealing with bacterial and, to some extent, viral infections has brought fungal infections to the fore as major causes of death, especially in higher risk categories of patients. Hemorrhage is a frequent complication owing to delayed megakaryocyte engraftment and thrombocytopenia during the early period and is a serious problem in patients with GVHD of the gut.
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PMID:Pathology of bone marrow in transplant recipients. 306 26

Syngeneic rat radiation chimeras treated transiently with cyclosporine (CsA) often develop a GVHD-like syndrome after discontinuing the drug. CsA also causes medullary involution and loss of medullary epithelium in the thymus. Chronic graft-versus-host disease (GVHD), a late occurring syndrome following bone marrow transplantation with many features of autoimmune diseases, is thought by many to result from a thymic deficiency leading to a failure to develop specific tolerance for the host. A direct connection between a thymic deficiency and chronic GVHD was tested by transferring thymocytes from CsA-treated syngeneic Lewis chimeras into irradiated Lewis secondary recipients. Nine of 10 of these recipients had evidence of chronic GVHD in skin biopsies taken at 3 weeks posttransplant or in the autopsies at 5 weeks. Changes included characteristic lichen planuslike infiltrates and sclerodermalike changes in the skin, characteristic infiltrates and myositis of the tongue, often chronic hepatitis with bile duct injury, and interstitial and ductal infiltrates in the serous salivary glands. Immunoperoxidase stains of the skin and tongue infiltrates showed a marked predominance of W3/25+:OX8- lymphocytes. The hair follicles had increased expression of Ia antigen. The thymus in the secondary recipient had variable thymocyte reconstitution of the cortex and a mild to marked reduction in the relative size of the medulla. Stains for cytokeratin showed a moderate to marked reduction of cortical epithelium and marked to total loss of the medullary epithelium. These studies demonstrate that the features of post-CsA syngeneic GVHD resembling chronic GVHD result from an abnormal thymic microenvironment. They also provide additional evidence linking a thymus deficiency with chronic GVHD.
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PMID:Transfer of cyclosporine-associated syngeneic graft-versus-host disease by thymocytes. Resemblance to chronic graft-versus-host disease. 325 8

Fifty-seven patients undergoing allogeneic marrow transplantation had persistent poor graft function after transplant and received a second marrow infusion from the original donor. Eight donors were HLA-non-identical family members and 49 were HLA-identical siblings. Poor function of the initial graft occurred in the absence of demonstrable rejection or persistent malignancy. Preparative reconditioning was not given before the second marrow infusion. Thirty-four of the 57 patients survived more than 1 month after the boost and were evaluated for haematopoietic recovery. All 34 subsequently achieved a neutrophil count of more than 500 X 10(6)/l and 20 became independent of platelet transfusions. Forty-nine (86%) of the 57 patients demonstrated acute graft-versus-host disease (GVHD). In 24 of the 49 patients GVHD increased in severity (10 patients) or first appeared (14 patients) after the boost. Chronic GVHD developed in all of the 20 patients who survived more than 150 days after the second infusion. Currently, 10 patients survive (median follow-up of more than 5 years) and all have normal haematologic function. Although haematologic reconstitution and increased GVHD occurred in some patients receiving second marrow infusions, the relation of these outcomes to the marrow boost is unclear in the absence of a control group.
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PMID:Second marrow infusion for poor graft function after allogeneic marrow transplantation. 333 16

Patients with haematological malignancies with HLA-identical marrow donors were randomized to treatment with cyclosporin (CSA) or methotrexate (MTX). Two of the 29 patients randomized to MTX died before engraftment compared with none of the 30 treated with CSA. Engraftment by leucocytes (P less than 0.0001), granulocytes (P less than 0.02), and reticulocytes (P less than 0.01) was faster among the CSA patients. There were no significant differences between the two groups regarding transfusions, hospitalization and incidence of early septicaemia. Granulocyte transfusions were required in seven of 29 MTX and two of 30 CSA patients (not significant: NS). Overall (grade I-IV) acute graft-versus-host disease (GVHD) was more common (P = 0.001) in the CSA patients. Grade II-IV acute GVHD was seen in 40% of the CSA patients compared with 22% in the MTX patients (NS). In the adult patients grade II-IV GVHD was slightly more common (P less than 0.05) in those treated with CSA compared with MTX. Chronic GVHD appeared in 30 and 39% in the two groups respectively. Actuarial 3-year survival was 58% for the CSA patients and 69% for the MTX patients. There were no significant differences regarding the incidence of interstitial pneumonitis or relapses between the two groups. The side-effects of CSA treatment includes nephrotoxicity (83%), hepatotoxicity (20%), hirsutism (43%), hypertension (23%), tremor (27%) and gingival hyperplasia (27%). Serum creatinine values were increased at 3 and 6 months in the CSA group but were within the normal range after 6 months. A blind study on oral side-effects revealed that CSA patients more often had a normal mucosa (P = 0.025) and less frequently had mucositis (P = 0.01) compared with the MTX group.
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PMID:A randomized trial comparing use of cyclosporin and methotrexate for graft-versus-host disease prophylaxis in bone marrow transplant recipients with haematological malignancies. 333 19

Chronic graft-versus-host disease (GVHD) is a complex immunological disease which can appear in up to 30% of survivors of allogeneic bone marrow transplantation. Target organs include skin, mucous membranes and liver; eventual mucosal defects, specifically involving secretory IgA, have been observed. In these studies we show that transplant recipients who develop GVHD are more likely to have higher serum antibody titres to bovine casein and circulating immune complexes containing casein than patients who do not develop this complication. The stage of GVHD may be related to the level of antibody to casein. The biological role of immune complexes in relationship to the evolution of this disease is unknown.
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PMID:Association of circulating immune complexes containing bovine proteins and graft-versus-host disease. 352 3

In random bred species including dog and man, a marrow graft from a donor genetically identical for the major histocompatibility complex is followed by significant graft-versus-host disease (GVHD) in 30% to 50% of the recipients despite the administration of postgrafting immunosuppression. Controlled trials comparing the immunosuppressive drugs methotrexate or cyclosporine have shown no differences in long-term survival, although cyclosporine reduces the incidence of mucositis and is associated with somewhat earlier engraftment. Observations in the canine model indicating efficacy of combining a brief course of methotrexate with the cyclosporine regimen are now being confirmed in patients with early results indicating a reduction in GVHD and an improved survival. In both species failure to administer immunosuppression after grafting is associated with a high incidence of acute GVHD and an adverse effect on survival. Removal of donor T cells from the marrow inoculum reduces the incidence of acute GVHD but at the risk of a higher likelihood of subsequent graft failure and maybe even leukemic recurrence. Results of studies in canine and human chimeras agree with murine data indicating a principal role for T cells in the pathogenic mechanism of GVHD. Chimera lymphocytes (of donor origin) from dogs and patients with acute GVHD show proliferative responses to previously stored host cells, and lymphocytes cytotoxic to host target cells are seen in patients with GVHD. Observations indicate a direct, rather than an indirect, role for T cells in GVHD. "Specific" suppressor cells may be responsible for maintaining stable graft-host tolerance while "nonspecific" suppressor cells may play a role in the impaired immune defenses in patients with chronic GVHD. Chronic GVHD, which resembles systemic collagen vascular disease, occurs in approximately 40% of HLA-identical recipients, particularly following acute GVHD and is more frequent in older patients. Efforts to treat both acute and chronic GVHD with prednisone, antithymocyte globulin, cyclosporine and azathioprine are only unpredictably effective. Data in dogs pointed out the feasibility of transplants from partially matched related donors or matched unrelated donors, an approach that is now being pursued in human patients. Marrow grafts from HLA-partially matched family members resulted in a higher incidence of acute GVHD. There was no difference in acute GVHD comparing class I to class II antigen differences and long term survival was influenced by patient age and disease status rather than HLA incompatibility.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Graft-versus-host disease after marrow transplantation. 354 Sep 90


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