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

In a series of 198 patients we compared various methods of prevention of GVHD. One hundred and thirty-three patients were treated with CSA alone, 44 with the combination of CSA and MTX, and 21 with CSA after marrow T cell depletion. The incidence of GVHD greater than or equal to II was 35% in the CSA group, 22% in the CSA+MTX group and 14% in the T depleted group. The actuarial survival was 55.4%, 52.3% and 55.1% respectively. These results show that the improvement of methods of prevention of GVHD did not affect significantly long term survival after BMT.
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PMID:Role of immunosuppressive drugs for prevention of graft-v-host disease after bone marrow transplantation. 267 32

Japanese patients with leukemia who received bone marrow from human leukocyte antigen (HLA)-compatible siblings had a low incidence of acute graft-versus-host disease (GVHD). Twenty-five (21%) of 120 patients developed moderate (grade II) to severe (grades III to IV) acute GVHD. Severe GVHD was only seen in patients older than 20 years of age. It is also notable that only 2 (5%) of 39 patients who received the combination of methotrexate and cyclosporine (MTX/CSP) for the prevention of GVHD developed grade II acute GVHD, and none developed grades III to IV acute GVHD. Thirteen (30%) of 44 patients receiving MTX alone and 10 (27%) of 37 patients receiving CSP alone developed grades II to IV acute GVHD. Multivariate life-table analysis indicated that the prophylaxis by MTX/CSP was the risk factor for the low incidence of grades II to IV acute GVHD. Compared with the reported incidence of acute GVHD in the patients of the United States, lower incidence of acute GVHD in Japanese BMT patients might be attributable to a lesser degree of genetic diversity in histocompatibility antigens among Japanese.
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PMID:Low incidence of acute graft-versus-host disease by the administration of methotrexate and cyclosporine in Japanese leukemia patients after bone marrow transplantation from human leukocyte antigen compatible siblings; possible role of genetic homogeneity. The Nagoya Bone Marrow Transplantation Group. 280 62

Patients with haematological malignancies and HLA-identical marrow donors were randomized to treatment with cyclosporin A (CSA, n = 30) or methotrexate (MTX, n = 29) with a follow-up ranging from 32 to 70 months. The two groups were comparable regarding disease status and age. Acute graft-versus-host disease (GVHD) was similar and the cumulative incidences of chronic GVHD was 42% in both groups. The overall incidence of cytomegalovirus (CMV) infection and other late infections were also the same in the two groups. Interstitial CMV pneumonitis occurred in 13% in the CSA group compared with 32% in the MTX group (ns). The probability of relapse was 42% after 4 years among the CSA patients and was significantly higher than the probability of relapse in the MTX patients which was found to be 10% (p = 0.03). The actuarial survival after 5 years was 53% for the CSA patients and 57% for the MTX patients (ns). The relapse-free survival was 41% and 59%, respectively (ns). There were no differences between the two groups in terms of renal or hepatic function, incidence of cataracts, blood cell counts, bone marrow cellularity or Karnofsky scores at 2 and 4 years after transplantation.
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PMID:An increased risk of relapse in cyclosporin-treated compared with methotrexate-treated patients: long-term follow-up of a randomized trial. 284 43

Graft-versus-host disease (GvHD) prophylaxis using methotrexate (23 patients) and T-cell depletion of the graft (40 patients) was compared in 63 allogeneic bone marrow transplantations (BMT) for leukaemia. T-cell depletion significantly reduced (p = 0.001) the incidence of GvHD from 68% to 11% and the GvHD-associated mortality from 79% to 5%. Actuarial disease-free survival for low-risk patients (57% with T-cell depletion and 47% with MTX) was not significantly improved, due to graft failure and possibly due to a higher leukaemic relapse rate after T-cell depletion. Prevention of graft failure after T cell-depleted BMT is essential and could also reduce the risk of leukaemic relapse by improved engraftment.
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PMID:T-cell depletion versus methotrexate as GvHD-prophylaxis in allogeneic bone marrow transplantation for leukaemia. 305 41

In Essen 121 bone marrow transplantations were carried out. The indications were severe aplastic anemia (n = 18), acute leukemia in relapse (n = 20), acute leukemia in remission (n = 46) or chronic myeloid leukemia (n = 37). The conditioning regimen consisted of cyclophosphamide or the combination of cyclophosphamide and total body irradiation. All patients were treated under strict gnotobiotic care. To mitigate the risk of CMV infections intravenous CMV-hyperimmunoglobulin and CMV-negative blood products have been applied routinely since two years. MTX was used as prophylaxis against GVH-disease. In case of severe aplastic anemia 13 patients (72%) are still alive with a median observation time of 24 months. In the prognostically unfavourable group of acute leukemia in relapse only one patient showed long term survival. In this patient leukemic relapse occurred six years after transplantation. The survival rate of AML patients grafted during the first remission is 55% (15/27) with a median observation time of 40 months. For patients grafted in first or consecutive remission of ALL the survival rate is 42% (5/12) with a maximal observation time of 29 months. Out of 37 patients grafted because of CML, eight were in an advanced stage of the disease. 13 patients are still alive, the maximal observation time is 37 months. The overall incidence of GVHD in patients at risk was 28% in aplastic anemia, 26% in AML, 9% in ALL and 63% in CML. In aplastic anemia no patient developed an interstitial pneumonia. In leukemia the risk of fatal interstitial pneumonia was 34%.
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PMID:Bone marrow transplantation in severe aplastic anemia and acute or chronic leukemia. 351 96

A new regimen for prevention of acute graft-versus-host disease (GvHD)--OKT3 (murine monoclonal anti-pan-T antibody), prednisone and methotrexate (OKT3-pred-MTX)--was compared with the Minnesota standard regimen--antithymocyte globulin, prednisone and methotrexate (ATG-pred-MTX)--for adverse effects, effect on incidence of acute GvHD, and survival at 1 year post-transplant. Twenty patients (aged 25 +/- 9 years) had bone-marrow transplantation (BMT) from their HLA-MLC identical sibling donors for treatment of aplastic anaemia (four), acute leukaemia in remission (13) or chronic myelogenous leukaemia (three). These 20 patients received (OKT3-pred-MTX) on days 8-22 post-transplant. Results of this group are compared to those of 19 concurrent patients (aged 26 +/- 12 years) who received ATG-pred-MTX on days 8-22 post-transplant. On the first day of treatment, 20/20 OKT3 patients and 18/19 ATG patients were febrile. Within 24 h of the first dose of OKT3, 6/20 patients experienced dyspnoea or chest pain and 3/20 patients developed diarrhoea. No further adverse effects were seen after the second dose of OKT3 and no late adverse effects were attributed to this drug. Time to engraftment (means 25 d) was not statistically significantly different in the two prophylactic groups. Acute GvHD was diagnosed in 14 of 20 patients who received OKT3-pred-MTX and in eight of 19 patients who received ATG-pred-MTX (P = 0.06). The incidence of hepatic or gastrointestinal GVHD (greater than or equal to grade 2) was similar in the two groups: 4/20 OKT3-pred-MTX, 6/19 ATG-pred-MTX. Characteristics of post-transplant infections were also similar for the two prophylactic groups. Survival at 1 year post-transplant was 65% for patients who received OKT3 and 44% for patients who received ATG (P = 0.13). The use of OKT3 with prednisone and methotrexate is relatively safe and is associated with a similar incidence of moderate-severe acute GvHD to that experienced in the use of ATG with prednisone and methotrexate.
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PMID:Graft-versus-host disease prophylaxis with anti-T-cell monoclonal antibody OKT3, prednisone and methotrexate in allogeneic bone-marrow transplantation. 389 Sep 26

Methotrexate has been used as the mainstay therapy to prevent or ameliorate graft-versus-host disease (GVHD) in allogeneic bone marrow transplantation. We began a nonrandomized study in which methotrexate was not given routinely. Fifty-five patients underwent transplant for acute leukemia (44 patients), aplastic anemia (6 patients), and other malignancies (5 patients). Methotrexate was given to 34 patients (MTX +) and was withheld in 21 patients (MTX -). Median (range) age of patients was 12 (0.8-43) years in the MTX + group, and 16 (3-45) years in the MTX- group. Mean days (+/- SEM) to engraftment (neutrophils greater than 500/microL, and platelets greater than 20,000/microL untransfused) occurred earlier in the MTX- patients (19.6 +/- 1.4 v 24.9 +/- 1.8 days for granulocytes, and 19.3 +/- 1.5 v 27.4 +/- 2.8 days for platelets, P less than .05). There were no statistically significant differences between the patient groups for the incidence or severity of GVHD (10/34 in the MTX + group had grade O-l GVHD compared to 9/21 in the MTX- group). The interstitial pneumonitis occurred at a significantly increased rate in patients who received methotrexate (15/34) compared to those patients who did not (3/21) (P = .02). However, there was also a significant relationship between the interstitial pneumonitis and the preparative regimen: if the preparative regimen contained 1,000 rad single fraction total body irradiation, 8/14 patients were affected compared to 5/22 patients affected when 1,200 rad fractionated total body irradiation was used (P = .03). Because methotrexate significantly retards hematopoietic reconstitution, randomized trials for GVHD prevention are recommended.
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PMID:Incidence of acute graft-versus-host disease with and without methotrexate prophylaxis in allogeneic bone marrow transplant patients. 637 59

Our studies have provided further data to support the concept of resistance to engraftment in the dog. Resistance seems to be mediated by antigens coded for by loci different from but linked to DLA. Resistance can be abrogated by the addition of viable lymphoid cells to the marrow inoculum, by high-dose (fractionated) TBI of the recipient and by MTX given postgrafting. CyA has an adverse effect on engraftment probably by interfering with the graft-facilitating effect of donor lymphocytes. GVHD following allogeneic marrow transplantation appears to be mediated by DLA and non-DLA antigens. GVHD can be prevented or ameliorated in recipients of DLA identical littermate marrow by postgrafting CyA or MTX. With DLA nonidentical or unrelated grafts MTX or even more so a combination of MTX and CyA appear to be able to induce tolerance in some recipients.
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PMID:Marrow graft studies in dogs: factors influencing resistance to engraftment and graft-versus-host disease. 676 39

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


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