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)

Antithymocyte and antilymphocyte globulins (ALG) are currently used as immunosuppressive agents in organ transplantation and for the treatment of acute graft-versus-host disease and aplastic anemia. Since any type of immunosuppressive treatment is known to carry the risk of developing B-cell lymphoproliferative disorders, we investigated the in vitro effect of ALG on human B-cell activation and proliferation. The data demonstrate that whatever the source of lymphocytes used for ALG preparation (thymocytes, thoracic duct lymphocytes, B- or T-cell lines), (1) ALG react with both B- and T-cell lines, and (2) ALG contain antibodies specific for B cells (eg, CD21) or common to T and B cells (eg anti-beta 2-microglobulin, anti-HLA-DR, CD18, CD11a) in addition to T-cell-specific antibodies. Unlike all other T-cell mitogens tested (Concanavalin A [Con A], Pokeweek mitogen [PWM], CD3 and CD2 antibodies), ALG do not trigger B-cell differentiation into immunoglobulin-secreting cells at concentrations which induce maximum T-cell proliferation. This effect could be attributed to a direct interaction of ALG with B lymphocytes as shown by the capacity of ALG to block the response of purified B cells to a variety of activators. Furthermore, all the ALG tested were shown to inhibit the proliferation of six of the seven Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and six of the seven Burkitt's lymphoma cell lines studied. This selective B-cell antiproliferative property of ALG was not reproduced with CD11a, CD18, CD21, CD24, or anti-HLA-DR monoclonal antibodies (MoAbs). These results suggest that, although suppressing T-cell responses, ALG treatment may directly control B cell proliferation to some extent, in keeping with the relatively low risk of posttransplant lymphoproliferative disorders reported with ALG.
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PMID:Antiproliferative effect of antilymphocyte globulins on B cells and B-cell lines. 156 43

The diagnosis of cerebral toxoplasmosis in an immunosuppressed patient is based on computer tomography (CT) findings and response to specific empiric treatment. Although infrequent, cerebral toxoplasmosis has been described in patients undergoing bone marrow transplantation (BMT) with lesions compatible with this diagnosis always being found on cranial CT. The case of a patient with Burkitt's lymphoma who received BMT and developed convulsive crisis with repeatedly normal cranial CT scans during the course of severe immunosuppression (graft versus host disease and treatment with 3 immunosuppressive drugs) is presented. Post mortem study demonstrated cerebral cysts of Toxoplasma gondii with slight perilesional inflammatory infiltrate. Normal CT in patients with neurologic foci and severe immunosuppression following BMT does not exclude the diagnosis of cerebral toxoplasmosis, therefore more sensitive diagnostic techniques should be performed, particularly in areas in which infection by toxoplasma is endemic.
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PMID:[Cerebral toxoplasmosis with atypical presentation in a bone marrow transplant patient]. 798 3

Stem cell transplantations were performed in 69 children at Siriraj Hospital over a ten year period. The source of stem cells was bone marrow (60), peripheral blood (3), or cord blood (6). The diseases treated included 35 thalassemias, 11 Burkitt's lymphoma, five non-Hodgkin's lymphoma, five aplastic anemia, eight acute leukemia, and one each of neuroblastoma, severe combined immunodeficiency, Wiskott-Aldrich syndrome, myelodysplastic syndrome, and pyruvate kinase deficiency. The success rate of stem cell transplantation in Thai children varied according to the underlying diseases of the patients, ranging from 50% in acute leukemia to 100% in aplastic anemia. The outcome of stem cell transplantation in 35 thalassemic children revealed 23 (79.4%) were cured, whereas three (10.3%) remain alive with disease and the other three (10.3%) died. The incidence of graft-versus-host disease was low hen compared with that of Western countries. It is concluded that bone marrow, peripheral blood and cord blood stem cell transplantation will be the treatment of choice and will be widely used in the future to cure many hematologic and malignant disorders in children.
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PMID:Bone marrow, peripheral blood and cord blood stem cell transplantation in children: ten years' experience at Siriraj Hospital. 988 40

We report a 10-year-old male with widespread recurrent Burkitt's lymphoma who underwent successful mismatched unrelated cord blood transplantation (UCBT) following salvage chemotherapy. He was conditioned with TBI, antithymocyte globulin (ATG) and high-dose VP-16 and achieved full donor engraftment. He experienced grade II skin and grade I gastrointestinal acute GVHD with no chronic GVHD. He is alive with no evidence of disease 24 months following UCBT. Bone Marrow Transplantation (2000) 25, 1311-1313.
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PMID:Successful treatment of relapsed Burkitt's lymphoma using unrelated cord blood transplantation as consolidation therapy. 1087 39

We have performed an allogeneic stem cell transplant in an 18-year-old male patient who had Burkitt's lymphoma. The patient had disease which was refractory to conventional intensive chemotherapy and radiation therapy. High-dose chemotherapy with autologous stem cell rescue was given but the patient relapsed within 2 months after transplantation. He was then treated with allogeneic stem cell transplantation using a fludarabine, busulfan and anti-thymocyte globulin-based conditioning regimen. His GVHD prophylaxis included mycophenolate and tacrolimus. The patient had engraftment within 14 days. Investigation by FISH showed more than 95% of his peripheral blood nucleated cells to be of donor origin since day +14. He is now alive and well and remains disease-free 6-months after the transplant. A graft-versus-lymphoma effect is thought to be one of the factors contributing to his remission.
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PMID:Allogeneic stem cell transplantation in a patient with refractory Burkitt's lymphoma using non-myeloablative conditioning regimen. 1122 78

While modern intensive chemotherapy protocols cure the majority of patients with Burkitt's lymphoma, the prospects of cure with salvage chemotherapy for relapsed or refractory disease are minimal. There are limited data on the results of allografting for well characterised Burkitt's lymphoma and in particular little on the impact of GVHD on transplant outcome. We report a patient with t(8;22) Burkitt's lymphoma who underwent an HLA-identical sibling allograft in second complete remission. Relapse occurred at day 60 post-transplant, without pre-existing GVHD. GVHD subsequently developed after withdrawal of immunosuppression and administration of alpha-interferon. Concomitantly the lymphoma regressed, consistent with a graft versus Burkitt's effect, until progression at day 200. A delayed, partial and transient response subsequently occurred to rituximab, a chimeric monoclonal antibody against the CD20 antigen. These observations suggest that immunotherapeutic approaches should be considered for Burkitt's lymphoma unable to be cured by conventional chemotherapy.
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PMID:Graft versus Burkitt's lymphoma effect after allogeneic marrow transplantation. 1215 81

To investigate the problem of allogeneic bone marrow transplantation (allo-BMT) for advanced stage patients, we retrospectively analyzed 24 consecutive patients who underwent allo-BMT in the non-remission stage. Twenty-four patients (19 males and 5 females) with acute leukemia, chronic myelogenous leukemia, and malignant lymphoma underwent allo-BMT. The patients had a median age of 30 years. There were eight cases of acute myelogenous leukemia (AML), six cases acute lymphocytic leukemia (ALL), nine cases of chronic myelogenous leukemia (CML), and one case of Burkitt's lymphoma. The 3-year overall survival rate was 22.5%, with a median survival time of 206 days in AML, 345 days in ALL, and 363 days in CML. Overall survival was associated with a recovery of platelets of less than 30 days and an acute graft-versus-host disease (acute GVHD) presence of less than grade II ( p=0.042). Fourteen patients died of transplantation-related diseases. Our important problem is to decrease transplantation-related deaths in allo-BMT during the non-remission stage, and longer survival can be expected with better pretreatment and prophylaxis for GVHD. In addition, the selection of the source of hematopoietic stem cell transplantation at an optimal time is considered to be another problem to be approached.
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PMID:Long-term outcome after allogeneic bone marrow transplantation for hematological malignancies with non-remission status. Results of a single-center study of 24 patients. 1242 40

Relapse is a major problem after allogeneic transplantation in children with acute B-lineage lymphoblastic leukemias (ALL) and lymphomas and additional therapeutic strategies are needed to increase graft versus leukemia effects without inducing graft versus host disease (GvHD). Several studies have shown the efficacy of a humanized CD20 antibody (rituximab) for treatment of CD20+ malignancies together with conventional chemotherapy but less is known about its post transplant usefulness. We studied the ability of rituximab to mediate antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) with effector cells and complement from patients who were transplanted with T-cell-depleted grafts from unrelated or mismatched related donors. Highest lytic activity (ADCC) was observed against leukemia-derived MHH4 cells and Burkitt's lymphoma-derived Raji cells in the first months after transplantation, corresponding to the high percentage of regenerating CD56+ CD16+ cells. Moreover, primary cryopreserved ALL-blasts from a pediatric patient were also efficiently lysed. Increased lysis was obtained after stimulation with interleukin-2. Combination of ADCC and CDC had additive effects. These findings encourage clinical trials on the use of rituximab for improving minimal residual disease control and relapse prevention after allogeneic high-risk transplantation in the small group of pediatric patients with CD20+ leukemias/lymphomas.
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PMID:Rituximab mediates in vitro antileukemic activity in pediatric patients after allogeneic transplantation. 1590 73

Patients with relapsed diffuse large B-cell lymphoma (DLBCL) who have failed or are ineligible for autologous haematopoietic cell transplantation (HCT) have a poor prognosis. We examined the outcomes of non-myeloablative allogeneic HCT in this setting. Thirty-one patients with DLBCL and one patient with Burkitt lymphoma received allogeneic HCT following 2 Gy total body irradiation with or without fludarabine. Median age was 52 years. Twenty-four patients (75%) had undergone prior autologous HCT. Disease status at HCT was complete response (14/32, 44%), partial response (9/32, 28%), or refractory (9/32, 28%). Cumulative incidences of acute graft-versus-host disease (GVHD) grades II-IV, grades III-IV, and chronic GVHD were 53%, 19%, and 47% respectively. With a median follow-up of 45 months, 3-year estimated overall (OS) and progression-free survival (PFS) was 45% and 35% respectively. Three-year cumulative incidences of relapse and non-relapse mortality were 41% and 25% respectively. In multivariate models, chemosensitive disease and receipt of >or=4 lines of treatment before HCT were associated with better OS. Patients with chemosensitive disease had 3-year OS and PFS of 56% and 43% respectively. Non-myeloablative allogeneic HCT can produce long-term disease-free survival in patients with chemosensitive relapsed DLBCL who have failed or are ineligible for autologous HCT.
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PMID:Non-myeloablative allogeneic haematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: a multicentre experience. 1875 62

Patients with chemorefractory aggressive non-Hodgkin's lymphomas (NHL) generally have poor clinical outcomes with available therapies. Allogeneic transplantation may be curative, but few studies are available to guide transplant decision making in this setting. We examined allogeneic transplantation outcomes for 46 patients with chemorefractory, aggressive NHL patients who had either stable disease (SD; n = 32) or progressive disease (PD; n = 14), respectively, following last salvage treatment. The median age was 46 years (range: 22-63 years). Thirty-nine patients received matched sibling allografts, whereas 7 underwent unrelated donor transplantation. Diagnoses included diffuse large B-cell lymphoma (n = 18), Burkitt's lymphoma (n = 3), transformed B cell lymphoma (n = 5), mantle cell lymphoma (n = 11), and peripheral T cell lymphoma (n = 9). The median number of prior therapies was 3 (range: 2-8). Median follow-up of surviving patients is 5 years. Five-year overall survival (OS), progression-free survival (PFS), and relapse rate for the whole cohort (n = 46) were 38%, 34%, and 35%, respectively. The rate of grade II-IV acute graft-versus-host disease (aGVHD) was 43%. Of the 33 evaluable patients 75% developed chronic GVHD (cGVHD). Overall nonrelapse mortality (NRM) rate was 34%. The 5-year OS and PFS rates for patients with SD and PD were 46% versus 21% (P = .01; log-rank test), and 46% versus 7% (P = .0002; log-rank test), respectively. This study confirms that allogeneic transplant is curative for a subset of chemorefractory patients with SD. However, patients with PD had uniformly poor outcomes following allografting with conventional conditioning approaches. Given the outcomes seen here in the setting of PD, such patients should proceed with transplant only in the setting of investigational therapy.
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PMID:Allogeneic stem cell transplantation for patients with relapsed chemorefractory aggressive non-hodgkin lymphomas. 1936 46


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