Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of bone marrow transplantation is increasing in the management of advanced cancers. In autologous bone marrow transplantation (ABMT), many investigators have attempted to purge the graft of residual tumor cells because of concern that reinfused tumor cells might contribute to relapse. The feasibility of various methods (exposure to chemical agents, monoclonal antibodies (MoAbs), toxins, dye, magnetic microparticles ... ) has been confirmed. In allogeneic bone marrow transplantation, clinical studies have related the prevention of graft-versus-host disease reaction through the partial depletion of T lymphocytes in the donor graft limited to 1 log to maintain a graft-versus-leukemia (GVL) effect. Similarly, the feasibility of different assays (soybean agglutinin, Moabs and magnetic microparticles) have been shown. However, the clinical benefit of BM purging remains to be demonstrated. For ABMT, only recent data on B-cell lymphoma and leukemia strongly support the clinical usefulness of an ex-vivo purging. For allogeneic BMT, one question remains controversial: is T lymphocytes depletion the best method for GVHD prevention?
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PMID:[Ex-vivo treatment of a bone marrow graft]. 160 93

Studies in the 38C13 model, a lethal murine B-cell lymphoma of C3H origin, have previously demonstrated the efficacy of immunization with tumor idiotype against established tumors, especially in the setting of reduced tumor burden when combined with chemotherapy. We have extended these studies to test the protective effect of immunization with 38C13 idiotype protein (38C-Id), coupled to KLH and administered with an adjuvant, against a subsequent tumor challenge following lethal total body irradiation (950 R) and reconstitution with syngeneic bone marrow (20 x 10(6) cells) from normal donors. Animals prepared in this manner which were immunized with 38C-Id after 3 weeks recuperation and challenged with 1000 38C13 tumor cells 2 weeks later demonstrated significantly longer survival when compared to control animals which had been immunized with irrelevant idiotype protein. Irradiated reconstituted mice immunized after 5 weeks recuperation and challenged with 1000 tumor cells also demonstrated prolonged survival compared to controls, as well as a small number of cures (approximately 40%). Anti-38C-Id antibodies, implicated in the mechanism of idiotype induced anti-tumor immunity in this model, were detectable after immunization at both 3 and 5 weeks, although there was no significant correlation between serum antibody levels and survival of individual mice. These results suggest that immunologic recovery as early as 3 to 5 weeks following marrow grafting is sufficient to allow induction of idiotype-specific, anti-tumor immunity and form a model for our clinical trial of tumor idiotype vaccination for patients with B-cell lymphoma undergoing autologous BMT.
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PMID:Idiotype vaccination post-bone marrow transplantation for B-cell lymphoma: initial studies in a murine model. 179 39

A 64-year-old woman underwent an ileocecal resection for ileus. The specimen revealed a diffuse large B cell lymphoma. The diagnosis was stage IIA non-Hodgkin's lymphoma. She received chemotherapy with the CHOP-etoposide regimen, resulting in partial remission. High-dose etoposide was used for PBSC mobilization before auto-PBSCT. Conditioning was ranimustine, carboplatin, etoposide and cyclophosphamide. Her renal function deteriorated gradually, starting 3 months post-PBSCT. Eight months post-transplant, serum creatine concentration was 7.1 mg/dl, and BUN was 59.2 mg/dl. Her hemoglobin concentration decreased to 5.3 g/dl, with no evidence of hemolysis. Renal biopsy revealed fibrous crescent formations in glomeruli, and mononuclear cell infiltration in interstitial spaces. Renal injury in this patient differs from BMT nephropathy, which is similar to hemolytic uremic syndrome, and represents another type of late renal injury after PBSCT.
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PMID:Crescentic glomerulonephritis developing 3 months after autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma. 981 4

Between June 1988 and May 1996, 428 patients underwent allogeneic BMT (288 related donor (RD) and 140 unrelated donor (UD)) at the Vancouver General Hospital. Eight patients (UD six and RD two) developed a post-transplant lymphoproliferative disorder (PTLD). Median age at BMT was 38 years (range 22-51). Five of the six UD allografts were T cell depleted. Cyclosporine+/-methotrexate was used for GVHD prophylaxis. All eight patients developed GVHD; in six this was refractory to treatment with corticosteroids. Rabbit antithymocyte globulin (ATG) or an anti-CD5-ricin A chain immunotoxin (Xomazyme) was used as second-line therapy for GVHD. Presentation with PTLD occurred at median day 90.5 (range 34-282) post BMT. Five of the eight patients had a rapidly progressive course characterized by fever, lymphadenopathy, lung and liver involvement and died within 3-8 days. PTLD was an incidental finding at post mortem examination in two patients. The remaining patient had localized disease and recovered. Pathological analysis revealed two morphological patterns; diffuse large B cell lymphoma (DLBC lymphoma, five patients) and polymorphous B cell hyperplasia (PBCH, three patients). EBV expression was positive in all eight cases and monoclonality was demonstrated in seven cases. In multivariate analysis, T cell depletion of the allograft (P=0.0001, relative risk (RR)=30.5), anti-T cell therapy for GVHD (P=0.006, RR=12.7) and acute GVHD grades 3-4 (P=0.04, RR=7.7) were the significant factors for development of PTLD. In conclusion, we have identified two forms of PTLD after BMT: one is characterized by disseminated disease with a rapidly progressive and often fulminant course and the other by localized, relatively indolent disease. Morphology, EBV positivity and clonality do not appear to correlate with the clinical course. The major risk factors for development of PTLD after BMT are ex vivo T cell depletion of the allograft and in vivo anti-T cell therapy for GVHD.
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PMID:Lymphoproliferative disorders following allogeneic bone marrow transplantation: the Vancouver experience. 984 95

A 38-year-old man with refractory follicular lymphoma underwent allogeneic BMT from an HLA-identical sibling donor. He had generalized lymphadenopathy, hepatosplenomegaly and lymphoma infiltration of the marrow, all of which disappeared within 3 months following transplantation. Six months post-transplant, progressive hepatomegaly developed in the absence of splenomegaly and lymphadenopathy, and he died from hepatic failure. Autopsy disclosed diffuse large B cell lymphoma of the liver, into which the follicular lymphoma had transformed. Future issues to be investigated should include the optimal timing of allogeneic BMT for low-grade lymphomas.
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PMID:Histologic transformation of follicular lymphoma after allogeneic bone marrow transplantation. 1101 52

The goal of the current study was to determine whether whole bone marrow cells or splenic CD8(+) T cells from C57BL/6 (H-2(b)) donor mice, which are tolerant to BALB/c (H-2(d)) alloantigens, are capable of mediating graft anti-tumor activity against a BALB/c B-cell lymphoma after injection into irradiated BALB/c hosts. The experimental results show that high doses of splenic CD8(+) T cells mixed with T cell-depleted bone marrow cells from C57BL/6 non-tolerant (normal) donors eliminate the BCL(1) B-cell lymphoma cells and induce lethal graft-versus-host disease (GVHD). CD8(+) T cells from tolerant donors simultaneously lose both their ability to induce GVHD and their anti-tumor activity. Whole bone marrow cell transplants from normal donors eliminated BCL(1) tumor cells without inducing GVHD, and bone marrow cells from tolerant donors failed to eliminate the tumor cells. The infused BCL(1) tumor cells expressed an immunogenic tumor-specific idiotype antigen disparate from host alloantigens, indicating that recognition of the tumor-specific antigen alone was insufficient to elicit graft anti-tumor activity from unimmunized allotolerant donor splenic CD8(+) T cells or whole bone marrow cells. We conclude that CD8(+) T cells from unimmunized normal donor mice require alloantigen recognition to mediate their anti-tumor activity following allogeneic BMT.
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PMID:Alloantigen recognition is critical for CD8 T cell-mediated graft anti-tumor activity against murine BCL1 lymphoma after myeloablative bone marrow transplantation. 1760 12

Hematopoietic SCT (HSCT) has become a curative therapeutic strategy for several malignant and nonmalignant diseases. We report the comprehensive results of the first 10 years of experience in HSCT from the two major BMT units in Lebanon: Makassed University Hospital and the American University of Beirut Medical Center. The median and the 5-year overall survival (OS) were 97 months and 58%, respectively, for the 84 patients who received allogeneic HSCT, and 60 months and 50%, respectively, for the 228 patients who received autologous BMT. The results for myeloablative allogeneic transplantation were as follows: AML (n=28, 5-year OS 58%, 5-year disease-free survival (DFS) 48%), CML (n=9, 5-year OS 66%, 5-year DFS 52%), ALL (n=13, 2-year OS 10%, 2-year DFS 10%), thalassemia (n=10, 5-year transfusion-free survival 67%). The results for autologous HSCT were as follows: diffuse large B-cell lymphoma (DLBCL) in relapse (n=37, 5-year OS 68%, 5-year progression-free survival (PFS) 65%), Hodgkin's lymphoma (n=55, 5-year OS 55%, 5-year PFS 36%), and first-line multiple myeloma (n=71, 5-year OS 53%, 5-year PFS 24%). For allogeneic transplanted patients, the cumulative TRM was 23% and the incidence of acute GVHD was 23%. For autografted patients, TRM was 2.6%. These results indicate that despite the relatively low socioeconomic status of the Lebanese population, both allogeneic and autologous HSCT are feasible with outcomes similar to developed countries.
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PMID:Hematopoietic stem cell transplantation in Lebanon: first comprehensive report. 1872 16