Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, donor lymphocyte infusions have been successfully used to treat patients with CML who have relapsed following allogeneic bone marrow transplantation (BMT). Responses can be achieved in more than 60-70% of patients with stable phase CML without the need for the additional high dose cytotoxic chemotherapy that would accompany a second transplant procedure. The clinical and molecular remissions induced by this approach are a clear demonstration of graft-versus-leukemia (GVL) activity. Although undoubtedly donor lymphocyte infusions are safer than a second BMT, they are associated with toxicities stemming from graft-versus-host disease (GVHD) and pancytopenia. In this review, the immunomodulatory mechanisms underlying the GVL activity of donor allogeneic lymphocytes infusions are presented. Unresolved issues regarding lymphocyte administration are discussed as well as potential ways to limit complications due to GVHD and pancytopenia. New potential applications of this immunotherapeutic approach for treatment of infectious disease and non-hematologic malignancies will be presented.
 ...
PMID:Immunomodulatory effects of donor lymphocyte infusions following allogeneic bone marrow transplantation. 858 96

This report documents a case of squamous cell carcinoma (SCC) of the tongue in a child with Fanconi anemia (FA). FA is an autosomal recessive syndrome defined by chromosomal breakage in response to diepoxybutane or mitomycin C in which many patients present with pancytopenia, hypoplastic bone marrow, hyperpigmentation of the skin, skeletal malformations, small stature, hypogonadism, and chromosomal aberrations. Such patients are prone to the development of hematological malignancies and squamous cell carcinoma, especially of the head and neck. Although FA appears to be genetically heterogeneous, all cases display abnormalities of DNA repair. A gene defective in one of the four subsets of FA patients has been defined. Defects in this gene are thought to play a role in the development of neoplasia in FA patients. However, many other factors may also contribute to the development of malignancies, including immune deficiencies, therapeutic strategies, and bone marrow transplantation. This report reviews the association of FA and SCC and highlights the many factors involved in the development of neoplasia within a single patient, including FA, cyclophosphamide, immunosuppression, X-irradiation, and chronic oral graft-versus-host disease. In addition, the human papillomavirus status, although negative, is documented for the first time in such a case.
 ...
PMID:Squamous cell carcinoma of the tongue in a child with Fanconi anemia: a case report and review of the literature. 859 46

Peripheral blood and cord blood are increasingly used as sources of hematopoietic stem cells. They offer several advantages over bone marrow-derived stem cell grafts and are expected to replace bone marrow transplantation for treatment of malignant hematological disorders and solid tumors. Since the benefit of bone marrow transplantation for treatment of victims of radiation accidents has been seriously questioned, it is reasonable to examine if these alternative stem cell sources may change future strategies. Cord blood is attractive since it is an immediately available and fully characterized allogeneic stem cell source. However, experience with transplants in children suggests that recovery times are too long to benefit a victim of a radiation accident. Because of their potential to rapidly restore hematopoiesis, peripheral blood stem cells may currently be the best stem cell source for a patient who is expected to die from the consequences of prolonged pancytopenia (and not from damage of nonhematopoietic tissue). However, before getting accepted as the optimal stem cell source, the risk of acute and chronic GVHD must be confirmed to be low and unrelated donors must be shown to accept the potential risk of treatment with mobilizing agents. Future strategies should aim at developing methods of transiently rather than permanently engrafting allogeneic stem cells, since essentially all patients exposed to high doses of irradiation are expected to recover autologous marrow function.
 ...
PMID:Is blood a better source of allogeneic hematopoietic stem cells for use after radiation accidents? 864 Jan 57

Donor lymphocyte infusions for treatment of relapse after allogeneic bone marrow or stem cell transplantation is being used with increasing frequency. Study of this form of adoptive immunotherapy will shed light on different aspects of cell-mediated cytotoxicity such as antigen presentation, processing, immune recognition, lymphocyte subsets involved, and mechanism of cell death. Donor lymphocyte infusions are extremely effective for cytogenetic relapses or chronic-phase relapses of chronic myelogenous leukemia, but are less effective in acute leukemias or other disorders. Donor lymphocyte infusions are associated with a significant risk of morbidity and mortality due to graft-versus-host disease and pancytopenia. Lower cell doses, earlier infusions, and selective depletion of CD8+ lymphocytes have been proposed as methods of diminishing these toxicities. Current research is focusing on methods of making donor lymphocyte infusions more effective in the nonchronic myelogenous leukemia setting, and decreasing their toxicity without losing their clinical efficacy in the treatment of relapsed chronic myelogenous leukemia.
 ...
PMID:Donor lymphocyte infusions. 872 1

A 49-year-old man with a 3-year history of chronic lymphocytic leukemia (CLL, stage B at diagnosis) responded well to four course of fludarabine, but developed marrow failure and prolonged pancytopenia lasting 9 months following the fifth course. Fludarabine therapy could not be continued due to pancytopenia, eventually resulting in disease progression. Bone marrow transplantation from an unrelated donor mismatched at one DRB1 locus and both DQB1 loci was performed as salvage therapy. The marrow was depleted of T cells with Campath-1G. Pre-transplant immunosuppression was enhanced with 600 cGy total lymphoid irradiation and Campath-1G infusions in addition to 120 mg/kg cyclophosphamide and 1200 cGy fractionated total body irradiation. Cyclosporine alone was used as post-transplant immunosuppression. Neutrophils reached 0.5x10(9)/1 on day 14 and platelets 50 x 10(9)/1 on day 40. No acute graft-versus-host disease was seen. Bulk disease detected on CT scanning prior to BMT was found to have disappeared 10 weeks after BMT. The marrow showed residual disease (5% CD5+/CD19+ cells) 9 weeks after transplantation, which had decreased markedly at 13 (0.5%) and 26 (0.4%) weeks. The patient is currently alive and well 10 months after BMT with no clinically detectable disease. We conclude that BMT from an unrelated donor is a feasible treatment option in advanced CLL.
 ...
PMID:T cell-depleted allogeneic bone marrow transplantation from a partially HLA-mismatched unrelated donor for progressive chronic lymphocytic leukemia and fludarabine-induced bone marrow failure. 873 15

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.
 ...
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

Clinical aspects, pathogenesis and risk factors of transfusion-associated graft versus host disease(TA-GVHD) are summarized. TA-GVHD should be suspected when fever, rashes, diarrhea, liver dysfunction and marrow aplasia occurred 14-30 days after blood transfusion. Almost all the patients suffering from this complication died from severe pancytopenia and grave infection in spite of intensive treatments. Although TA-GVHD have been thought as a rare disease which occurs only in immunosuppressed patients, it is clear now that TA-GVHD may also occur even in immunocompetent patients, in case of so called one-way matching pair of HLA antigens between recipient and donor. When they receive blood without any different HLA antigens from their own, they can neither recognize it non-self nor reject it and at last they may suffer from TA-GVHD. One-way matching of HLA antigens between recipient and donor is important as a risk factor of TA-GVHD especially in immunocompetent patients. Though there is no effective treatment after the onset of this complication, both autologous transfusion and irradiation of blood before transfusion are known to be clearly effective to prevent this complication.
 ...
PMID:[One-way matching of HLA antigens between recipient and donor as a risk factor of transfusion-associated GVHD]. 930 Dec 83

Graft-versus-host disease in solid organ transplantation is very rare, but the prognosis is poor when the condition causes pancytopenia. We report a case of graft-versus-host disease in a heart-lung transplant recipient who at 2 weeks after transplantation had development of features of graft-versus-host disease, including bone marrow aplasia, that could not be attributed to drugs or viral infections. The diagnosis was confirmed by skin biopsy and demonstration of chimerism of peripheral lymphocytes. Augmentation of immunosuppression with intravenous methylprednisolone resulted in improvement in liver function but had no effect on the pancytopenia. Mediastinal irradiation was given with increase in both white blood cell and platelet counts. Unfortunately the patient eventually died of gastrointestinal bleeding and fungemia.
 ...
PMID:Mediastinal irradiation for graft-versus-host disease in a heart-lung transplant recipient. 932 50

Donor leukocyte infusions (DLI) are an effective therapy for patients who relapse with leukemia after bone marrow transplantation (BMT). Severe graft-versus-host disease and prolonged periods of pancytopenia compromise the success of this treatment in a substantial number of patients. We used filgrastim-mobilized peripheral blood progenitor cells (PBPCs), in some cases preceded by cytoreductive therapy, to circumvent some of the problems associated with DLI. Eleven patients (median age 41 years) received a total of 20 donor cell infusions. Their diagnosis was CML in hematological (two patients) or cytogenetic relapse (two patients), six patients suffered from acute myeloid leukemia (AM; n = 5) or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL Ph+). One patient had multiple myeloma (MM). All six patients with acute leukemias received cytoreductive therapy prior to PBPC infusions; three patients with CML were pretreated with IFN alpha. Four of four patients with CML responded to PBPC infusions and currently are in complete clinical and molecular remission for time periods between 1 and 12 months. Six of six patients with acute leukemias achieved a complete remission. All of them relapsed after a median remission duration of 24 weeks (range 11-49 weeks). Three patients relapsed at extramedullary sites (CNS, testes, skin). Four of six acute leukemia patients received further cytoreductive therapy. All patients responded again and are in complete remission for time periods between 14 and 615 days. Two patients with acute leukemias have died due to dissemination of the disease. The patient with MM did not respond and is alive with disease. Severe (grade III) acute GVHD developed in two of 11 patients, three patients developed grade II disease, six patients did not show any signs of GVHD. Extensive chronic GVHD has developed in two cases to date. Patients with chemotherapy prior to PBPC infusion developed neutropenia and thrombocytopenia with a maximum duration of 20 and 14 days, respectively; prolonged periods of neutropenia did not occur. Two patients developed long-lasting thrombocytopenia in spite of PBPC infusion, in one case followed by leukemic relapse. Repeated courses of chemotherapy and PBPC infusion were generally tolerated well; no early deaths due to treatment-related toxicity or GVHD were observed. We conclude that the use of allogeneic PBPC instead of DLI in patients with relapse after BMT is technically feasible and safe. The efficacy of PBPC infusions seems comparable to DLI in patients with CML. Patients with acute leukemias also achieved complete albeit transient remissions. Aggressive chemotherapy followed by PBPC infusions resulted in only limited duration of cytopenia. The usage of PBPC infusion instead of non G-CSF-mobilized donor cells for treatment of relapse after BMT may reduce pancytopenia-related complications and merits further investigation.
 ...
PMID:Allogeneic peripheral blood progenitor cells for treatment of relapse after bone marrow transplantation. 933 54

To increase the stem cell content of T cell-depleted bone marrow transplants (BMT), we treated 12 patients with hematological malignancies with BMT from HLA-identical sibling donors given G-CSF 10 microg/kg/day for 5 days before marrow harvest. After CD34+ cell selection, patients received a median of 1.7 (range, 0.82-3.1) x 10(6) CD34+ cells/kg and 2.3 (range, 0.25-4.0) x 10(5) CD3+ cells/kg. All patients had initial engraftment but four developed pancytopenia between days 55-130 post-BMT. In two patients, this required a second infusion of G-CSF-mobilized donor peripheral blood progenitor cells. We observed no delayed pancytopenia in a matched historical group of 24 patients receiving T cell-depleted BMT without prior G-CSF stimulation. Compared to this control group, G-CSF-stimulated marrow recipients showed a significant decline in neutrophil and monocyte counts after 8 weeks. However, outcome after BMT was otherwise comparable, with a similar incidence of acute graft-versus-host disease and transplant-related mortality. Disease-free survival was 63 vs 67% for controls matched for CD34+ cell dose (P = NS). These results indicate that G-CSF stimulation can increase the CD34+ cell content of T cell-depleted marrow but carries a risk of late graft failure.
 ...
PMID:T cell-depleted granulocyte colony-stimulating factor (G-CSF) modified allogenic bone marrow transplantation for hematological malignancy improves graft CD34+ cell content but is associated with delayed pancytopenia. 953 34


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>