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)

Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity after allogeneic bone marrow transplantation, but can be avoided by removing T lymphocytes from the donor bone marrow. However, T-cell depletion increases the risk of graft rejection. This study examined the use of CD52 monoclonal antibodies to eliminate T cells from both donor marrow and recipient to prevent both GVHD and rejection. Seventy patients receiving HLA-identical sibling transplants for acute myelogenous leukemia (AML) in first remission were studied. An IgM (CAMPATH-1M) was used for in vitro depletion of the graft and an IgG (CAMPATH-1G) for in vivo depletion of the recipient before graft infusion. No posttransplant immunosuppression was given. Results were compared with two control groups: (1) 50 patients who received bone marrow depleted with CAMPATH-1M, but no CAMPATH-1G in vivo; and (2) 459 patients reported to the International Bone Marrow Transplant Registry (IBMTR) who received nondepleted grafts and conventional GVHD prophylaxis with cyclosporin A (CyA) and methotrexate (MTX). The incidence of acute GVHD was 4% in the treatment group compared with 35% in the CyA/MTX group (P <.001). Chronic GVHD was also exceptionally low in the treatment group (3% v 36%; P <.001). The problem of graft rejection, which had been frequent in the historic CAMPATH-1M group (31%), was largely overcome in the treatment group (6%). Thus, transplant-related mortality of the treatment group (15% at 5 years) was lower than for the CyA/MTX group (26%; P =.04). There was little difference in the risk of leukemia relapse between the treatment group (30% at 5 years) and the CyA/MTX group (29%). Survival of the treatment group at 6 months was better than the CyA/MTX group (92% v 78%), although at 5 years the difference was not significant (62% v 58%) and neither was the difference in leukemia-free survival (60% v 52%). We conclude that T-cell depletion is a useful strategy to prevent GVHD, provided that measures are taken to ensure engraftment. Using CAMPATH-1G to deplete residual host lymphocytes is a simple and practical method to do this. At least in AML, the beneficial reduction in GVHD can be achieved without an increased risk of relapse.
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PMID:Improving the outcome of bone marrow transplantation by using CD52 monoclonal antibodies to prevent graft-versus-host disease and graft rejection. 984 24

Chronic graft-versus-host disease (GVHD) is the most common late complication of allogeneic bone marrow transplantation (BMT). The sclerodermatous form of the disease is often refractory to standard treatment modalities. Based on reports of response to etretinate, a synthetic retinoid, among patients with scleroderma, we have added etretinate to the treatment regimen of 32 patients with refractory sclerodermatous chronic GVHD. This case series is comprised mainly of patients who had chronic GVHD of long duration (median of 30 months before the initiation of etretinate). Most had failed to respond to three or more agents before etretinate treatment was started. Clinical response was assessed after 3 months of therapy. Five patients did not complete a 3-month trial. Among the 27 patients evaluable for response, 20 showed improvement including softening of the skin, flattening of cutaneous lesions, increased range of motion, and improved performance status. Four showed no response after 3 months of therapy and 3 had progression of their sclerosis. Overall, etretinate has been fairly well tolerated in our patients, with skin breakdown and/or ulceration leading to its discontinuation in 6 patients. We believe the results in our patients are encouraging and suggest that further evaluation of etretinate in the treatment of sclerodermatous chronic GVHD is warranted.
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PMID:Etretinate therapy for refractory sclerodermatous chronic graft-versus-host disease. 986 47

A five-agent GVHD prophylaxis programme consisting of cyclosporin A, methotrexate, anti-thymocyte-globulin, pentaglobin and metronidazol was given to 48 recipients of unrelated donor marrow with chronic myelogenous leukemia, acute leukemia, myelodysplastic syndromes, and familiar lymphocytic hemophagocytosis of an average age of 33.5 (0.6-56) years. GVHD grades II-IV occurred in 18 patients (39%) and grades III-IV in five patients (11%). Chronic GVHD developed in nine patients (23%), three limited and six extensive. Fifteen patients died. Clinical relapse was detected in eight patients. Four patients died as a consequence of the underlying disease and subsequent treatment, 11 patients died of transplant-related causes. After a median follow-up of 19 months, the overall and disease-free survival are 67% and 62%, respectively. Survival by age is as follows: 0-19 years: 12/13 patients; 20-39 years: 14/25 patients; 40-59 years: 7/10 patients. The five-agent GVHD prophylaxis regimen is effective. Matched-unrelated donor transplants can be carried out safely in patients younger than 50 years of age. The results in patients younger than 20 years of age should encourage matched-unrelated donor transplants at earlier stages of the disease.
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PMID:Use of a five-agent GVHD prevention regimen in recipients of unrelated donor marrow. 1033 43

The transplantation of placental/umbilical cord blood (P/CB) has been used successfully to reconstitute bone marrow function in both related and unrelated recipients. We report here the experience of the New York Blood Center P/CB Program. Since its inception in 1992, over 400 unrelated transplants were supported between July 1993 and September 1997. Overall, event-free survival for all diagnoses and ages approached 0.45. Success and rapidity of engraftment correlated most strongly with the degree of human leukocyte antigen (HLA) disparity and cell dose/kg body weight recipient. Acute graft-versus-host disease (GVHD) was common in all patients but, surprisingly, did not differ between those patients who received grafts having one or more antigen mismatches. Chronic GVHD was uncommon and only rarely contributed to death. These results demonstrate the feasibility of large-scale P/CB banking for the provision of cryopreserved stem cell preparations for unrelated transplants. The degree of the program's success argues strongly for additional P/CB banks in order to increase the likelihood of finding a suitable stem cell preparation for patients for whom related matched donors do not exist.
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PMID:The Placental/Umbilical Cord Blood Program of the New York Blood Center. A progress report. 1037 35

One hundred and fifty five pediatric patients underwent allogeneic bone marrow transplantation between 1980 and 1996 in the St Anna Children's Hospital in Vienna with an overall survival of 52.3% (81 patients). Seventy-three patients with a minimum observation time of 1 year (1-13 years, median: 4.6) were analyzed retrospectively for chronic GVHD, organ toxicity (WHO score), growth and pubertal development. Chronic GVHD was diagnosed in 20 patients (27.3%), being extensive in 17 cases. Maximum organ toxicity was WHO III in two patients (3%) and WHO II in 11 patients (15%) 1 year after BMT and WHO III in one patient (2%) and WHO II in five patients (11%) 3 years after BMT. Impaired growth and pubertal development were detected in more than 30% 3 years after BMT. As all patients presented with a Karnofsky or Lansky score of more than 80%, they were asked to complete a questionnaire comprising 12 questions concerning physical state of health and psychosocial state of health. Restricted contacts were classified as imposing a severe handicap by six patients (8%), restriction in mobility and 'normal life activities' by three patients (4%) and two patients classified themselves as severely physically handicapped. Most patients (75%) reported no physical or psychical impairment.
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PMID:Organ toxicity and quality of life after allogeneic bone marrow transplantation in pediatric patients: a single centre retrospective analysis. 1037 72

Chronic graft-versus-host disease (GVHD) is a common late complication of allogeneic bone marrow transplantation (BMT) and is the principal cause of morbidity and non-relapse mortality. The improved management of acute GVHD has not translated into lower rates of chronic GVHD as older patients undergo allogeneic BMT, more patients receive unrelated or related mismatched allogeneic BMT, and donor lymphocyte infusion is increasingly used for treatment of post-BMT relapses. Patients with high risk chronic GVHD or those who fail on standard therapy have a bad prognosis. Salvage therapies have produced disappointing results. Here, we present a retrospective analysis of 26 patients where a steroid sparing synergistic combination of mycophenolate mofetil (MMF) and tacrolimus was used in refractory chronic GVHD. 46% patients showed an objective response, 11.5% had stable disease, 34.6% had progression and 7.7% were not evaluable. The combination was well tolerated. This promising preliminary result has prompted a trial to assess the safety and efficacy of this regimen in patients with chronic GVHD who have failed prior therapy and to determine if it would improve survival as well as quality of life in such patients.
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PMID:Salvage therapy for refractory chronic graft-versus-host disease with mycophenolate mofetil and tacrolimus. 1122 81

Low-dose cyclosporine (CsA), starting at 1 mg/kg/day i.v. with early discontinuation, and four doses of methotrexate (MTX), was given to 82 consecutive leukaemic patients receiving HLA-identical sibling marrow transplants. Retrospective controls (n = 40) received CsA, starting at 5-7.5 mg/kg/day i.v., given for 1 year, and MTX. In the low-dose group, the risk of acute GVHD grades I-II was 78% as compared to 57% among the controls (P < 0.01). The risk of acute GVHD grades III-IV was 2% and 5%, respectively (NS). Chronic GVHD occurred in 60% in the low-dose group and 24% in the controls (P < 0. 001). Extensive chronic GVHD did not differ between the groups (3% vs6%). In multivariate analyses, low-dose CsA was the only factor associated with acute GVHD grades I-IV (P = 0.02). Significant risk factors for chronic GVHD included low-dose CsA (P = 0.002) and CML (P = 0.03). Transplant-related mortality at 3 years post-BMT was 22% and 19%, in the low-dose group and controls, respectively (NS). The probability of relapse was 26% in the low-dose group and 53% in the controls (P = 0.06). In multivariate analysis, high-dose CsA was the strongest risk factor for relapse (P = 0.03). The 3-year relapse-free survival was 58% in the low-dose group and 43% in the controls (P = 0.1).
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PMID:Low-dose cyclosporine of short duration increases the risk of mild and moderate GVHD and reduces the risk of relapse in HLA-identical sibling marrow transplant recipients with leukaemia. 1049 Jul 28

Between January 1983 and December 1997, 88 patients (36 female, 52 male, median age 37 years, range 19-57) with chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) at the University Hospital of Vienna. Sixty patients were in chronic phase, 18 in accelerated phase, and ten in blast crisis. Marrow donors were HLA-identical siblings for 64 patients (BM 58, PBSC 6), 2-antigen-mismatched related donors (RD) for two, HLA-identical unrelated donors (URD) for 17, and 1-antigen-mismatched URD for five. The median time from diagnosis to BMT was 22 months (range 2-91), and 63 patients had received prior interferon (IFN)-alpha therapy, 46 (73%) for more than 6 months. Conditioning therapy consisted of cyclophosphamide (CY) and total body irradiation (TBI) in 71 patients and CY and busulfan (BU) in 16. One patient received etoposide and TBI. For graft-versus-host disease (GVHD) prophylaxis methotrexate (MTX) was given to 12 patients, MTX and cyclosporin A (CSA) to 67, CSA alone to four, and CSA and methylprednisolone to five. Durable engraftment was documented in 80 of 82 patients (98%). As of December 31, 1997, 52 patients (59%) were alive, 38 (58%) after sibling transplantation with a median observation time of 73 months and 14 (64%) after URD transplantation with a median observation time of 12 months. Probability of overall survival is 59%, for patients undergoing transplantation in chronic phase and 44% for patients undergoing transplantation in advanced stage CML. Probability of disease-free survival (DFS) after sibling and URD BMT is 55% and 59%, respectively. Ten patients (12%) experienced relapse of CML. Transplant-related mortality was 32% both after RD and after URD transplantation. Acute GVHD occurred in 53 of 80 evaluable patients (66%), consisting of grade III or IV in 14 patients (18%). Chronic GVHD developed in 40 of 63 eligible patients (63%), including extensive disease in 26 patients (41%). Thus, sibling and URD BMT offer high cure rates with acceptable toxicity to patients with CML.
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PMID:Long-term follow-up of patients after related- and unrelated-donor bone marrow transplantation for chronic myelogenous leukemia. 1060 94

To minimize immunosuppression, allow a graft-versus-leukemia (GVL) effect, and reduce relapse incidence, 73 leukemic recipients of human leukocyte antigens-identical sibling marrow were given graft-versus-host disease (GVHD) prophylaxis based on the estimated risk of GVHD development. Methotrexate (MTX) monotherapy was given to patients with an estimated low risk of developing GVHD, whereas MTX + cyclosporine (CsA) was given to 'high-risk' patients. After engraftment, CsA was discontinued, and weekly MTX was reinstituted and given until 3 months post-bone marrow transplant. Conditioning consisted of busulfan (BU) + cyclophosphamide (CY) (n = 35) or CY + total body irradiation (TBI) (n = 38). Retrospective controls were given CY + TBI and MTX + CsA (n = 39). The median observation time was 5 yr 11 months. Chronic GVHD increased to 53% in the individual BU + CY group and 46% in the individual CY + TBI group, compared to 25% in the control group (p = 0.05). This increase was restricted to the limited form. The actuarial relapse incidence decreased to 20% in the individual BU + CY group, compared to 52% in the control group, p = 0.03. In the individual CY + TBI group, the relapse incidence was 44% (n.s. versus controls, p = 0.04 versus individual BU + CY). The 5-yr relapse-free survival (RFS) in the individual BU + CY group was 66%, in the control group, 41% (p = 0.07), and in the individual CY + TBI group, 45% (p = 0.1 versus individual BU + CY). Patients with early leukemia in the individual BU + CY group had a RFS of 83%, compared to 44% in the control group (p = 0.02) and 42% in the individual CY + TBI group (p = 0.01). In the multivariate analysis, advanced leukemia beyond first complete remission and first chronic phase and conditioning with CY + TBI were correlated to poor RFS. In summary, the individualized prophylaxis itself did not reduce the relapse incidence. However, in patients with early leukemia conditioning with BU + CY, our method of individualizing the GVHD prophylaxis might be of value, since this group had the best RFS in this study.
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PMID:Improved survival after bone marrow transplantation for early leukemia using busulfan-cyclophosphamide and individualized prophylaxis against graft-versus-host disease: a long-term follow-up. 1061 42

Fifty-three patients with standard risk leukemia who underwent allogeneic peripheral blood stem cell transplantation (alloPBSCT) from their HLA-identical siblings were analyzed for engraftment, incidence and severity of GVHD, and relapse rate. Standard risk leukemia was defined as AML in first complete remission or CML in first chronic phase within the first year after diagnosis. The median age was 34.5 years (range 13-47). Stem cells were mobilized by using 10 microg/kg G-CSF subcutaneously for 5 days. A median of 5. 7 (2.1-21.4) x 106/kg CD34+ cells was collected over a median of 2 (range 1-5) apheresis procedures. Cyclosporin A (CsA) plus short-course MTX were used for GVHD prophylaxis. Recovery to granulocytes >0.5 x 109/l and platelets >20 x 109/l occurred at a median of day +13 (range 8-32) and +13 (range 8-51), respectively. Day +100 transplant-related mortality was 13.2% (7/53). Acute GVHD occurred in 20 of 49 (41%) evaluable patients and only six (12.3%) of them had severe disease (grade III-IV). Chronic GVHD occurred in 30 of 42 (71.4%) evaluable patients. Relapse rate at 2 years was 7. 5%. The median overall and leukemia-free survivals were 22 (4-44) and 20 (3-44) months, respectively. Estimated 4 year leukemia-free and overall survival rates were 60% and 62%, respectively. In conclusion, alloPBSCT in standard risk leukemia seems to be associated with a low relapse rate and no increased risk of acute GVHD, but there is a trend for higher incidence of cGVHD. Bone Marrow Transplantation (2000) 25, 1229-1232.
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PMID:Allogeneic peripheral blood stem cell transplantation for standard risk leukemia: experience of Ibni Sina Hospital. 1087 26


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