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)

In our BMT Unit, we have observed a high frequency of skin rash associated with fever and other clinical findings during engraftment of autologous BM and/or PBSC. Thirty patients with breast cancer and 12 patients with Hodgkin's or non-Hodgkin's lymphoma, treated with the same regimen, were analyzed retrospectively or prospectively to characterize the clinical syndrome, its frequency, and its clinical course, as well as to define the factors affecting its incidence. In patients developing skin rash, the median and range for time to onset of skin rash and for time to increase in WBC after reinfusion of stem cells were identical (8 days, range 5-13) and did not differ significantly (P = 0.533). Twenty-three patients (55%) had skin rash, 18 patients had fever. Other, less frequent manifestations include platelet transfusion refractoriness (PTR), diarrhea, diffuse alveolar hemorrhage, and autoimmune thrombocytopenia or hemolytic anemia. A higher proportion of breast cancer patients developed the syndrome in comparison to lymphoma patients (67% vs 25%, P = 0.051). Acute GVHD grade I-II was established histologically in six patients with the syndrome. Comparison of the incidence of the syndrome by different variables using Fisher's exact test revealed significance for disease category (P = 0.02) and number of previous treatment regimens (P = 0.002) as predictive factors for developing the autoaggression syndrome. In other words, patients with breast cancer and those with only one previous treatment regimen were more likely to develop the syndrome. This study suggests that an autoaggression GVHD-like syndrome accompanies the early phase of autologous engraftment and that a higher frequency of the syndrome might be seen in breast cancer patients undergoing high-dose chemotherapy and autologous stem cell transplantation.
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PMID:Increased frequency of autoaggression syndrome associated with autologous stem cell transplantation in breast cancer patients. 911 5

Donor lymphocyte infusions, by virtue of a graft-versus-tumor effect, have been shown to induce remissions in leukemia that recurs after allogeneic bone marrow transplantation. Similar effects have been postulated to contribute to the decreased recurrence rate observed after allogeneic transplantation in non-Hodgkin's lymphoma. This lower recurrence rate may be due to a variety of other mechanisms. We aimed to evaluate the role of graft-versus-lymphoma effects in patients in whom lymphomas recur after allogeneic transplantation. At the time of recurrence, immunosuppressive therapy was withheld. Patients with non-responding disease received an infusion of donor lymphocytes. Patients were observed for response and graft-versus-host disease. Disease in four of nine patients responded to withdrawal of immunosuppressive therapy. A minor response was observed in one of three recipients of donor lymphocyte infusions. Responses were observed among two patients with follicular lymphoma, one with large cell lymphoma and one with lymphoblastic lymphoma. A minor response was observed in a patient with prolymphocytic leukemia/lymphoma. We conclude that withdrawal of immunosuppressive therapy and donor lymphocyte infusion can induce durable remissions in patients with recurrent lymphoma after allogeneic transplantation.
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PMID:Management of lymphoma recurrence after allogeneic transplantation: the relevance of graft-versus-lymphoma effect. 916 41

Graft-versus-host disease (GVHD) is most commonly seen as a complication of bone marrow transplantation, although it can occur whenever tissue or blood products are given whereby immunologically competent donor lymphocytes react against host tissues. A 65-year-old man with non-Hodgkin's lymphoma developed a severe widespread erosive eruption of the skin and mucosal surfaces. Clinically and histologically it was identical to cutaneous GVHD even though the patient had never received tissue or blood products. He failed to respond to conventional therapy for GVHD, but his skin improved significantly on treating his underlying lymphoma, which eventually proved fatal. There are two previous reports of GVHD associated with malignancy but we believe this to be the first case secondary to a lymphoma.
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PMID:Graft-versus-host disease-like eruption in a patient with non-Hodgkin's lymphoma. 927 42

We report the outcomes of 44 consecutive patients with non-Hodgkin's lymphoma (NHL) who participated in prospective studies of allogeneic transplantation after conditioning with thiotepa, busulfan and cyclophosphamide. Within a range of 27-57 years, the median age was 37. Of the 44 patients, 12 (27.2%) had high-grade lymphomas, 27 (61.4%) had intermediate-grade lymphomas, and five (11.3%) had low-grade lymphomas. Twenty-eight (63.6%) patients had chemotherapy refractory disease. Thirty (68.2%) patients had stage IV disease at the time of transplantation, involving the bone marrow in 19 (43.2%). Eight (18.1%) patients had undergone previous transplantation, and 13 (29.5%) patients had received high-dose CVP as induction within 2 months prior to transplantation. Thirty-eight (86.3%) patients had an HLA-identical donor, and 6 (13.6%) had a one-antigen mismatched related donor. Twenty (45.4%) patients received bone marrow and 24 (54.6%) received granulocyte colony-stimulating factor (G-CSF) mobilized stem cells. The graft-versus-host disease (GVHD) prophylaxis contained cyclosporine or tacrolimus in combination with either methylprednisolone in 32 (72.7%) patients or with methotrexate in 12 (27.2%) patients. The actuarial probability of disease-free survival at 2 years is 23% (95% CI 13%-40%). Donor stem cell use was associated with a significantly decreased risk of treatment-related toxicity (p < 0.001), but with an increased risk for GVHD and delayed fungal and viral infections. These infections are linked not only to the use of donor-stem cells, but also to the methylprednisolone in the GVHD prophylaxis regimen. Improvements in the outcome of patients with advanced NHL and undergoing allogeneic transplantation will depend on the development of effective and non-toxic regimens for conditioning, GVHD prophylaxis, and opportunistic infections prophylaxis.
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PMID:Allogeneic transplantation for recurrent or refractory non-Hodgkin's lymphoma with poor prognostic features after conditioning with thiotepa, busulfan, and cyclophosphamide: experience in 44 consecutive patients. 931 Jan 92

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

The Bone Marrow Transplantation Program in Belarus was founded in 1992, and in 1993, a Bone Marrow Transplantation Centre was created in Minsk. From February 1994 to April 1996, 19 allogeneic bone marrow, 16 autologous bone marrow and 10 autologous peripheral blood stem cell transplantations were performed. Reasons for transplantation included chronic myeloid leukemia, multiple myeloma, severe aplastic anemia, acute myeloid leukemia, acute lymphoblastic leukemia, progressive myelofibrosis, Hodgkin's disease, non-Hodgkin's lymphoma, and neuroblastoma. Among the patients were two liquidators involved in the Chernobyl cleanup activity, both of whom underwent allogeneic bone marrow transplantation. A variety of ablative preparative regimens were used, and blood progenitor cells were mobilized by treatment with Cytoxan and granulocyte colony-stimulating factor. Therapy-related deaths resulted from graft-versus-host disease, septic shock, veno-occlusive disease bleeding and intestinal pulmonary fibrosis. Because the transplantation procedures were carried out on people who continued to be exposed to low-level irradiation, the post-transplantation period included a conservative strategy for prevention of graft-versus-host disease. There was nothing unusual about the post-transplantation period, although uncertainty about the continuing radiation dose should be taken into account when interpreting these data.
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PMID:The Chernobyl governmental program: two years of experience at the Belarusian Bone Marrow Transplant Centre. 936 16

Myeloablative conditioning associated with hazardous immediate and late complications is considered as a mandatory first step in preparation for allogeneic blood or marrow transplantation (allogeneic BMT) for the treatment of malignant hematologic disorders and genetic diseases. Immune-mediated graft-versus-leukemia (GVL) effects constitute the major benefit of allogeneic BMT. Therefore, we have introduced the use of relatively nonmyeloablative conditioning before allogeneic BMT aiming for establishing host-versus-graft tolerance for engraftment of donor immunohematopoietic cells for induction of GVL effects to displace residual malignant or genetically abnormal host cells. Our preliminary data in 26 patients with standard indications for allogeneic BMT, including acute leukemia (n = 10); chronic leukemia (n = 8), non-Hodgkin's lymphoma (n = 2), myelodysplastic syndrome (n = 1), multiple myeloma (n = 1), and genetic diseases (n = 4) suggest that nonmyeloablative conditioning including fludarabine, anti-T-lymphocyte globulin, and low-dose busulfan (8 mg/kg) is extremely well tolerated, with no severe procedure-related toxicity. Granulocyte colony-stimulating factor mobilized blood stem cell transplantation with standard dose of cyclosporin A as the sole anti-graft-versus-host disease (GVHD) prophylaxis resulted in stable partial (n = 9) or complete (n = 17) chimerism. In 9 patients absolute neutrophil count (ANC) did not decrease to below 0.1 x 10(9)/L whereas 2 patients never experienced ANC < 0.5 x 10(9)/L. ANC > or = 0.5 x 10(9)/L was accomplished within 10 to 32 (median, 15) days. Platelet counts did not decrease to below 20 x 10(9)/L in 4 patients requiring no platelet support at all; overall platelet counts > 20 x 10(9)/L were achieved within 0 to 35 (median 12) days. Fourteen patients experienced no GVHD at all; severe GVHD (grades 3 and 4) was the single major complication and the cause of death in 4 patients, occurring after early discontinuation of cyclosporine A. Relapse was reversed by allogeneic cell therapy in 2/3 cases, currently with no residual host DNA (male) by cytogenetic analysis and polymerase chain reaction. To date, with an observation period extending over 1 year (median 8 months), 22 of 26 patients (85%) treated by allogeneic nonmyeloablative stem cell transplantation are alive, and 21 (81%) are disease-free. The actuarial probability of disease-free survival at 14 months is 77.5% (95% confidence interval, 53% to 90%). Successful eradication of malignant and genetically abnormal host hematopoietic cells by allogeneic nonmyeloablative stem cell transplantation represents a potential new approach for safer treatment of a large variety of clinical syndromes with an indication for allogeneic BMT. Transient mixed chimerism which may protect the host from severe acute GVHD may be successfully reversed postallogeneic BMT with graded increments of donor lymphocyte infusions, thus resulting in eradication of malignant or genetically abnormal progenitor cells of host origin.
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PMID:Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. 944 33

We present the clinical results of allogeneic bone marrow transplantation (BMT) with T-cell-depleted grafts from HLA-matched sibling donors in patients with poor-risk relapsed low-grade non-Hodgkin's lymphoma (NHL). Poor risk was defined as relapse within 12 months after or progression during prior treatment. The conditioning regimen consisted of cyclophosphamide and total-body irradiation with or without additional idarubicin. Donor marrow was depleted of T lymphocytes using counterflow centrifugation. Post-BMT prophylaxis of graft-versus-host disease (GvHD) consisted of cyclosporine A. 15 patients with a median age of 47 years (range 30-57) were transplanted. All patients engrafted. After a median follow-up of 36 months (range 9-78), 10 patients were alive and in complete remission (CR). Two of them had relapsed after BMT but re-entered CR following infusions of leucocytes from the original bone marrow donor. Five patients died; causes of death were cardiomyopathy (n = 1), chronic GvHD (n = 1) and infection during chronic GvHD (n = 3). We conclude that allogeneic T-cell-depleted bone marrow transplantation is an efficacious treatment for patients with poor-risk relapsed low-grade NHL. Infusions of donor leucocytes reinduced CR in the two patients with relapse after BMT.
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PMID:Allogeneic bone marrow transplantation with T-cell-depleted marrow grafts for patients with poor-risk relapsed low-grade non-Hodgkin's lymphoma. 945 Aug 12

Acute bleeding after bone marrow transplantation (BMT) was investigated in 1,402 patients receiving transplants at Johns Hopkins Hospital between January 1, 1986 and June 30, 1995. Bleeding categorization was based on daily scores of intensity used by the blood transfusion service. Moderate and severe episodes were analyzed for bleeding sites. Analysis of the cause of death and the interval of the bleeding episode to outcome endpoints was recorded. Survival estimates were computed for 1,353 BMT patients. The overall incidence was 34%. Minor bleeding was seen in 10.6%, moderate bleeding was seen in 11.3%, and severe bleeding was seen in 12% of all patients. Fourteen percent of patients had moderate or severe gastrointestinal hemorrhage, 6.4% had moderate or severe hemorrhagic cystitis, 2.8% had pulmonary hemorrhage, and 2% had intracranial hemorrhage. Sixty-one percent had 1 bleeding site and 34.4% had more than 1 site. Moderate and severe bleeding was more prevalent in allogeneic (31%) and unrelated patients (62.5%) compared with autologous patients (18.5%). Significant distribution of incidence was found among the different diagnoses, but not by disease status in acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, Hodgkin's disease, and non-Hodgkin's lymphoma. Bleeding was associated with significantly reduced survival in allogeneic, autologous, and unrelated BMT and in each disease category except multiple myeloma. Survival was correlated with the bleeding intensity, bleeding site, and the number of sites. Although close temporal association was evident to mortality, bleeding was recorded as the cause of death in only the minority of cases compared with other toxicities after BMT (graft-versus-host disease, infections, and preparative regimen toxicity). Acute bleeding is a common complication after BMT that is profoundly associated with morbidity and mortality. Although bleeding was not a direct cause of death in the majority of cases, it has a potential prognostic implication as a predictor of poor outcome in clinical assessment of patients after BMT.
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PMID:Acute bleeding after bone marrow transplantation (BMT)- incidence and effect on survival. A quantitative analysis in 1,402 patients. 945 80

For patients with non-Hodgkin's lymphoma (NHL) undergoing blood or bone marrow transplantation (BMT), the use of autologous grafts has often been preferred to that of allogeneic stem cells because of a significantly lower incidence of non-relapse mortality. If complications associated with allo-BMT could be minimized without compromising efficacy, then it might become a preferred strategy for certain subsets of patients. In this report, we describe the toxicity and long-term efficacy of T cell-depleted allogeneic BMT using anti-CD6 monoclonal antibody and complement alone to reduce the risk of GVHD and its sequelae. Twenty-two patients, aged 18-60 years, with high (n = 10), intermediate (n = 9), or low (n = 3) grade NHL underwent HLA-identical allogeneic BMT from siblings. Patients had either relapsed after at least one remission or never achieved a full remission with chemotherapy. Twenty patients had a history of marrow involvement. Bone marrow was depleted of CD6+ T cells with T12 monoclonal antibody and complement as the sole form of GVHD prophylaxis. Stable hematopoietic engraftment occurred in all 22 patients. Four patients developed grade 2 and 1 patient grade 3 GVHD (23% grades 2-4 GVHD). Chronic GVHD has occurred in three patients. Treatment-related mortality was very low. Only one patient died while in remission. Thirteen patients are alive and free of disease with a median follow-up of 30 months. Estimated event-free and overall survivals are 54 and 59%, respectively. CD6 allogeneic marrow transplantation is associated with a low risk of transplant-related complications and may offer advantages for certain patients with recurrent NHL felt to be at high risk for relapse after autologous transplantation.
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PMID:CD6+ T cell-depleted allogeneic bone marrow transplantation for non-Hodgkin's lymphoma. 967 48


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