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 36-year-old woman with RAEB-t and severe bone marrow fibrosis undergoing autologous BMT, developed a histologically documented GVHD-like skin rash. Thereafter, autoimmune thyroiditis, autoimmune thrombocytopenic purpura and autoimmune hemolytic anemia and a lupus anti-coagulant (LAC) were diagnosed. The patient is still alive, symptom-free and in first complete remission (CR); however, all of the autoantibodies are still detectable, with the exception being the anti-erythrocyte antibody. The most outstanding feature of the present case is the polymorphism of the autoimmune events, in the absence of a coexisting systemic autoimmune disease. This patient has achieved long-term disease-free survival (DFS) in first CR despite high-risk MDS and the repeated immunosuppressant therapy required because of the complications described above; a GVL reaction somewhat similar to the autoimmune events may have contributed towards maintaining disease control.
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PMID:Multiple autoimmune events after autologous bone marrow transplantation. 915 54

A 32-year-old male received an allogeneic peripheral blood stem cell transplant (alloPBSCT) for myelodysplasia from his one HLA-A antigen mismatched brother. He is alive with trilineage engraftment and without active GVHD 200 days after transplant. In July 1986 he underwent orthotopic cardiac transplantation for viral cardiomyopathy and has received continuous immunosuppressive therapy. A post-transplant lymphoproliferative disorder with Hodgkin-like histopathology was diagnosed in August 1993 and was successfully treated with four cycles of MOPP chemotherapy. Due to persistent pancytopenia he underwent a bone marrow aspiration and biopsy in May 1996 which revealed monosomy 7 and morphologic changes compatible with myelodysplasia. This is the first report of a cardiac transplant recipient receiving an allogeneic hematopoietic stem cell transplant.
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PMID:Allogeneic peripheral blood stem cell transplant for myelodysplasia after chemotherapy for post-transplant lymphoma in a cardiac transplant recipient at 10 years. 915 71

In a double-blind, randomized study performed between 1988 and 1990, 40 patients undergoing allogeneic BMT from HLA-identical siblings for hematologic malignancies received 8 mg/kg/d rHuGM-CSF (molgramostim, n = 20) for 14 days. The median neutrophil count on day 14 was significantly higher in the GM-CSF group (1.90 vs 0.46 yen 10(9)/L, P < .0001). The incidence of acute GVHD and transplant-related mortality were comparable. Only two deaths occurred after 6 months; one due to pulmonary fibrosis in the GM-CSF group on day 1591, and one due to relapse on day 1590 in the placebo group. The Karnofsky score of the 10 survivors, 3 in the placebo group and 7 in the GM-CSF group, is 90-100% (median 100%), and none has chronic GVHD requiring therapy. There was no evidence of increased relapse in the GM-CSF group with only two relapses occurring; both in the placebo group. With a follow-up of 4.5-6.8 years (median 5.5 years), these patients are amongst the longest surviving patients to have received a recombinant growth factor post-allograft. We conclude that the administration of GM-CSF after allogeneic BMT does not appear to be associated with an increased incidence of chronic GVHD or relapse, or of other adverse effects such as the development of myelodysplasia.
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PMID:Long-term safety of GM-CSF (molgramostim) administration after allogeneic bone marrow transplantation for hematologic malignancies: five-year follow-up of a double-blind randomized placebo-controlled study. 915 59

Adoptive immunotherapy denotes the transfer of immunocompetent cells for the treatment of leukemia, cancer, or viral disease. It has regained much interest through the success of treating recurrent leukemia after allogeneic bone marrow transplantation with the transfusion of donor lymphocytes. Chimerism and transplantation tolerance toward the donor offer the possibility of adoptive immunotherapy using donor lymphocytes. In animal studies, donor lymphocytes could be transfused into the chimeric animal, if the transfusion was delayed after marrow transplantation. Transfused lymphocytes exhibit a graft-versus-leukemia effect and increase chimerism. Immunity could be transferred and immune reactivity toward new antigens improved. In human patients transfusion of donor lymphocytes was studied in leukemia recurring after marrow transplantation. It was very effective in the treatment of chronic myelogenous leukemia recurring after marrow transplantation. It was also effective in some patients with acute myeloid leukemia, myelodysplastic syndrome and myeloma; in acute lymphoblastic leukemia and lymphoma responses were rare. Responses in solid tumors as breast cancer have been described. Major complications are graft-versus-host disease and myelosuppression. Myelosuppression could be compensated by the transfusion of marrow. Graft-versus-host disease can be modified by the depletion of CD8-positive T cells from the lymphocyte concentrate or by transfusing very low numbers of cells and increasing doses in a stepwise fashion. The role of concomitant treatment with cytokines and activation of T cells by dendritic cells and vaccination remains to be defined.
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PMID:Adoptive immunotherapy with donor lymphocyte transfusions. 916 91

The immune-mediated graft-versus-leukemia effect is important to prevent relapse after allogeneic progenitor cell transplantation. This process requires engraftment of donor immuno-competent cells. The objective of this study was to assess the feasibility of achieving engraftment of allogeneic peripheral blood or bone marrow progenitor cell after purine analog containing nonmyeloablative chemotherapy. Patients with advanced leukemia or myelodysplastic syndromes (MDS) who were not candidates for a conventional myeloablative therapy because of older age or organ dysfunction were eligible. All patients had an HLA-identical or one-antigen-mismatched related donor. Fifteen patients were treated (13 with acute myeloid leukemia and 2 with MDS). The median age was 59 years (range, 27 to 71 years). Twelve patients were either refractory to therapy or beyond first relapse. Eight patients received fludarabine at 30 mg/m2/d for 4 days with idarubicin at 12 mg/m2/d for 3 days and ara-c at 2 g/m2/d for 4 days (n = 7) or melphalan at 140 mg/m2/d (n = 1). Seven patients received 2-chloro-deoxyadenosine at 12 mg/m2/d for 5 days and ara-C 1 at g/m2/d for 5 days. Thirteen patients received allogeneic peripheral blood stem cells and 1 received bone marrow after chemotherapy. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methyl-prednisolone. Treatment was generally well tolerated, with only 1 death from multiorgan failure before receiving stem cells. Thirteen patients achieved a neutrophil count of greater than 0.5 x 10(9)/L a median of 10 days postinfusion (range, 8 to 17 days). Ten patients achieved platelet counts of 20 x 10(9)/L a median of 13 days after progenitor cell infusion (range, 7 to 78 days). Eight patients achieved complete remissions (bone marrow blasts were < 5% with neutrophil recovery and platelet transfusion independence) that lasted a median of 60 days posttransplantation (range, 34 to 170+ days). Acute GVHD grade > or = 2 occurred in 3 patients. Chimerism analysis of bone marrow cells in 6 of 8 patients achieving remission showed > or = 90% donor cells between 14 and 30 days postinfusion, and 3 of 4 patients remaining in remission between 60 and 90 days continued to have > or = 80% donor cells. We conclude that purine analog-containing nonmyeloablative regimens allow engraftment of HLA-compatible hematopoietic progenitor cells. This approach permits us to explore the graft-versus-leukemia effect without the toxicity of myeloablative therapy and warrants further study in patients with leukemia who are ineligible for conventional transplantation with myeloablative regimens either because of age or concurrent medical conditions.
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PMID:Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. 919 77

High-dose therapy and allogeneic matched sibling bone marrow transplantation (BMT) is considered to be the treatment of choice for children with relapsed acute lymphoblastic leukemia (ALL), or for children with acute myeloid leukemia (AML) in first remission. However, the rate of bone marrow relapse after transplant for either of these diseases remains high. In this study, we assessed the efficacy and toxicity of high-dose cytosine arabinoside and total body irradiation (TBI) followed by allogeneic BMT, for children with acute leukemia or myelodysplastic syndrome (MDS). Sixty-five pediatric patients underwent allogeneic related (n = 57) or unrelated (n = 8) BMT. Twenty-seven were transplanted for ALL in second remission (CR2), and 16 for AML in first remission (CR1). The other 22 were high risk patients: six were transplanted for ALL in third remission (CR3), two for AML in CR2, two for myelodysplastic syndrome (MDS) and 12 for acute leukemia in relapse. Patients were prepared with cytosine arabinoside 3000 mg/m2 per dose twice daily for 6 days followed by 12000 cGy TBI as 200 cGy fractions twice daily for 3 days. Minimum follow-up is 21 months. Five-year event-free survival (EFS) and the actuarial relapse rate is 59 and 14% for patients with ALL in second remission, and 38 and 14+% for patients with AML in first remission. Twelve patients have relapsed (three are alive in remission after testicular or marrow relapse) and 28 have died of other causes. Acute GVHD with or without infection was the cause of death in 11 patients. Ten of the 11 patients who died of acute GVHD were considered at 'high risk' for GVHD (inadequate GVHD prophylaxis, or mismatched family donor or a matched unrelated donor). Toxicities in the immediate post-BMT period included diarrhea, oropharyngeal mucositis and conjunctivitis. Significant late toxicities included short stature, avascular necrosis of bone, and poor school performance (most often in patients who had received prior cranial irradiation). Our conclusions are that high-dose Ara-C and TBI followed by allogeneic bone marrow transplantation is effective therapy for children in second complete remission of their acute leukemia. However, significant late toxicities occur, and it is clear that more effective, less toxic therapies are necessary for these patients.
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PMID:Allogeneic bone marrow transplantation for children with acute leukemia: long-term follow-up of patients prepared with high-dose cytosine arabinoside and fractionated total body irradiation. 923 49

Bone marrow transplantation from unrelated donors is increasingly used to treat haematological malignancies. There are almost 4 million volunteer donors now available. Therefore, it is possible to find an HLA-A, -B and -DR-identical donor for around 70% of the patients. The major obstacles to unrelated bone marrow transplantations have been rejection, severe acute graft-versus-host disease (GVHD) and prolonged immune recovery leading to frequent infections and a high transplant-related mortality. However, with improved tissue typing using DNA techniques, immunosuppression using T-cell depletion in vitro or in vivo, the frequency of acute GVHD is acceptable and the results approach those obtained with HLA-identical siblings. For patients with chronic myeloid leukaemia, the worldwide 3-year survival is around 40%. Other indications for bone marrow transplantation with unrelated marrow include acute leukaemia and myelodysplastic syndromes with high-risk features. Unrelated cord blood cells and unrelated peripheral blood progenitor cells will be increasingly used as alternative haematopoietic stem cell sources to bone marrow. Improved immunosuppression, more accurate tissue typing, growth factors and better management of infections is expected to improve outcome using unrelated haematopoietic stem cells for transplantation in the near future.
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PMID:Bone marrow transplantation using unrelated donors for haematological malignancies. 923 6

Leukoencephalopathy probably caused by tacrolimus hydrate after stem cell transplantation in a girl with MDS 7 monosomy is reported. The conditioning regimen consisted of thiotepa (150 mg/m2 x 4), melphalan (70 mg/m2 x 2) and 12 Gy total body irradiation. She received peripheral blood CD34 positive cells (4.17 x 10(6)/kg) from her HLA-mismatched father and tacrolimus hydrate was used for GVHD prophylaxis. Engraftment was rapid and grade 1 acute GVHD of the skin responded well to pulse therapy. From day 27 she became irritable and sleepless, and right facial convulsions developed on day 37. No abnormality was found in the cerebrospinal fluid. Cranial CT findings showed no abnormalities except for low density lesions around the bilateral ventricle. Leukoencephalopathy was suspected and tacrolimus hydrate was discontinued. Thereafter psychosomatic symptoms improved, temporarily however, similar symptoms again developed following cyclosporine administration. Therefore we had to halt the administration of both tacrolimus and cyclosporine. She died on day 104 because of GVHD and fungal infection without recovering from leukoencephalopathy.
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PMID:[Leukoencephalopathy probably caused by tacrolimus hydrate after stem cell transplantation in a girl with MDS 7 monosomy]. 926 67

The relative benefit of allogeneic bone marrow transplantation (alloBMT) vs autologous BMT (autoBMT) for patients with relapsed or refractory Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) remains uncertain. Toxicity from graft-versus-host disease (GVHD) may diminish the potential benefits both of graft-versus-tumor activity and of receiving uncontaminated donor marrow stem cells. From 1987 to 1995, 27 adults (ages 18-60 years; median 36) underwent alloBMT for lymphoma after failure of standard chemotherapy. Twenty-one had NHL and six had HD (nodular sclerosis). Thirteen patients had primary refractory disease or chemotherapy-resistant relapses; two of these had relapsed after autoBMT. Three patients had untested relapses (one of them had relapsed after autoBMT), and 11 had chemotherapy-sensitive relapses. Twenty-four received HLA-matched bone marrow from a sibling (one twin); three received haploidentical marrow cells. Nine (33%) died from lymphoma. Eleven (41%) died of treatment-related causes. Opportunistic infections were a substantial problem leading to eight of these deaths (30%). Six patients (22%) survive free of lymphoma 17-70 months post-BMT (median, 56 months); four had had sensitive relapses, one had had a resistant relapse, and one had had nontested relapse. Three have chronic GVHD (limited in one; extensive in two). One HD patient who had relapsed after autoBMT remains in remission 19 months after alloBMT. No therapy-related myelodysplasia has been observed. We conclude that alloBMT has substantial morbidity in heavily pretreated lymphoma patients due to acute toxicity, infections and GVHD. However, 22% of our HD/NHL patients have had long-term disease-free survival.
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PMID:Allogeneic bone marrow transplantation for relapsed and refractory Hodgkin's disease and non-Hodgkin's lymphoma. 933 51

Treatment of recurrent leukemia after bone marrow transplantation with the transfusion of lymphocytes from the marrow donor has been successful in a majority of patients with chronic myelogenous leukemia and a minority of patients with acute myeloid leukemia and myelodysplastic syndrome. It has been disappointing in patients with acute lymphoblastic leukemia and in advanced stages of chronic myelogenous leukemia. In chronic-phase chronic myelogenous leukemia remissions were of good quality and the actuarial relapse rate was less than 20% at 3 years. In acute leukemias remissions were less durable. Graft-versus-host disease and marrow aplasia were the major complications of this form of treatment. In patients with marrow aplasia hematopoiesis could be restored by infusion of donor marrow without further conditioning treatment. Preceding or concomitant treatment with interferon alpha is not essential for a response, but the exact role of interferon alpha remains to be determined in a randomized study. Similarly, the best time for treatment remains to be defined. Treatment of cytogenetic and molecular recurrence of chronic myelogenous leukemia is most effective in preventing marrow aplasia, but a few patients may be treated unnecessarily, for some cytogenetic recurrences may remit spontaneously. The mechanism of the graft-versus-leukemia reaction is still not clear. Effector cells and target antigens remain to be defined. Observations are compatible with a graft-versus-host reaction directed against minor histocompatibility antigens presented at the cell surface of hematopoietic cells, but reactions against leukemia-specific antigens are possible. Future studies will focus on differences of reactions against possible leukemia-specific antigens and histocompatibility antigens on hematopoietic cells and cells of other organs.
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PMID:Donor leukocyte transfusions for leukemic relapse. 937 31


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