Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.1.1.69 (BMT)
2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A uniquely low incidence and death rate of interstitial pneumonia after allogeneic bone marrow transplantation for haemopoietic malignancy is described. Deduced from the comparison with results from a multicenter study, we conclude, that a) reduction of the dose rate to less than 5 rad/min, b) exclusion of CMV pos platelet donors and c) application of a CMV hyperimmune globulin are effectful means to reduce this most often deathly complication after BMT for haemopoietic malignancy.
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PMID:Interstitial pneumonia as a cause of early mortality in allogeneic bone marrow transplantation: the Viennese experience. 248 Mar 9

After marrow transplantation, major histocompatibility complex (MHC)-unrestricted natural killer (NK) lymphocytes are among the first cells to appear in the circulation. After T-cell-depleted bone marrow transplantation (TD-BMT), these cells have an activated pattern of target cell killing; they also secrete lymphokines including gamma-interferon (gamma-IFN), interleukin-2 (IL-2), and tumor necrosis factor (TNF) and may have a significant role as a primary defense against viral reactivation and in the elimination of residual host malignancy. We studied 43 patients with hematologic malignancy, treated by allogeneic TD-BMT, autologous nondepleted BMT, or chemotherapy alone to investigate (a) the mechanisms underlying the generation of these activated killer cells, (b) the range of conditions under which they are produced, and (c) their surface phenotype. We showed that gamma-IFN-secreting activated killer cells with the capacity to kill MHC-nonidentical NK-resistant targets are generated 4 to 6 weeks after either allogeneic TD-BMT or autologous BMT but do not appear after treatment with chemotherapy. Production therefore is not owing to T-cell depletion per se or to host donor alloreactivity, nor is it caused by stimulation by alloantigens contained in blood product support since no significant difference exists between allograft and chemotherapy patients in the number of units of blood platelet support given in the posttreatment period. Because most patients had no evidence of stimulation from virus reactivation/infection, the phenomenon of activation therefore appears to represent posttransplant immune disregulation following repopulation of the host immune system with lymphoid subsets derived exclusively from blood and marrow. Activated killing is predominantly mediated by the CD16+ CD3- subset, but substantial activity remains in the CD16- CD3+ cell fraction. Monoclonal antibodies (MoAbs) that block interaction with class-I MHC molecules at the level of target cell (W6/32 anti-HLA class I) or effector cell (CD8) do not inhibit killing by CD16- CD3+ cells. Activated killer cells may contribute to the lower risk of relapse after marrow transplantation as compared with intensive chemotherapy.
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PMID:Endogenously generated activated killer cells circulate after autologous and allogeneic marrow transplantation but not after chemotherapy. 249 37

In a retrospective analysis, patients with acute myelogenous leukemia (AML), treated in first complete remission (CR) with chemotherapy or with allogeneic or autologous bone marrow transplantation were compared with respect to their leukemia-free survival from CR. Two hundred and thirty-six patients treated with chemotherapy according to the EORTC AML-5 and AML-6 trials were included. The data of the transplanted patients were taken from two EBMT registries; 453 with an allogeneic and 182 with an autologous BMT. The very different sources of the data (trials and registries) forced us to be cautious in our conclusions. However, for the patient cohorts analyzed in the present study, BMT patients tended to have a better leukemia-free survival than chemotherapy patients. This was especially the case for the allogeneic BMT after 6 months of transplant.
Eur J Cancer Clin Oncol 1989 Mar
PMID:Treatment of acute myelogenous leukemia. An EBMT-EORTC retrospective analysis of chemotherapy versus allogeneic or autologous bone marrow transplantation. 259 45

Oral mucous membrane lesions were studied in 54 children below 12 yr of age treated with allogeneic bone marrow transplantation mainly because of hematological malignancies. Sixty-two percent of the children exhibited a wide range of oral side effects during therapy. Lesions observed during the first 2 wk prior to engraftment of the donor marrow were related to the chemo- and radiotherapy given. Oral ulcerations were seen in 34% of the children. Children given methotrexate as graft-versus-host disease (GVHD) prophylaxis exhibited oral ulcerations significantly (P less than 0.05) more often than those given cyclosporin. Oral lesions related to acute GVHD were only observed in two patients. Reactivating herpes simplex virus infection was seen in 35% of the children who were seropositive prior to BMT. An extensive oral candidiasis was observed in 15% of the patients. All six children with a chronic GVHD exhibited changes in the oral mucosa 2-4 yr after transplantation such as erythma of the mucous membranes, tongue atrophy and also lichenoid changes in the buccal mucosa.
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PMID:Oral mucous membrane lesions in children treated with bone marrow transplantation. 266 86

Nine children with poor prognosis neuroblastoma have been treated by continuous infusion of IL-2 and autologous LAK cells, as described previously by West et al. in adult patients. Six patients were in relapse after high-dose chemotherapy and autologous BMT and three presented with primary refractory disease after conventional therapy. Although patients were very young (median age 6 years; average weight 17 kg), infusion of IL-2, cytapheresis and reinjection of LAK cells appeared feasible with the usual and transient complications observed with IL-2. Haematological toxicity, although reversible, was more important than usually described and due to the presence of bone-marrow metastases in 8 of the 9 patients. Life-threatening toxicity was observed in only one of the admission centres and was probably due to the rapid reinjection of a very large number of activated cells. Two patients presenting with very active disease after high-dose chemotherapy and autologous or allogeneic BMT received IL-2 alone, at 120 days and at 90 days after the graft. The reactivation of grade-II GVHD was the major complication in the patient treated after an allograft, whereas no BMT-related toxicity was observed in the patient treated after the autologous BMT. Immunological modifications induced by IL-2 were very different between these patients. As expected, a preferential outgrowth of NK cells with both NK and LAK activity was observed in the patient treated just after the autograft. In contrast, in the patient treated after an allograft and in the 9 patients in relapse, T lymphocytes remained the major mononuclear cell population with a very large excess of CD8+ T cells. All patients progressed after the first induction cycle with the exception of the only patient treated after autologous BMT who reached a very good partial remission with disappearance of the local tumor and bone metastases. Although very preliminary, these data clearly show that the efficacy of IL-2 largely depends on the patient's immunological status with the optimal effect being observed when IL-2 is given in the first few months following an autograft.
Cancer Treat Rev 1989 Jun
PMID:A phase-II study of adoptive immunotherapy with continuous infusion of interleukin-2 in children with advanced neuroblastoma. A report on 11 cases. 267 Feb 9

Recipients of both allogeneic and autologous BMT demonstrate clinically significant immune deficiency involving T and B lymphocytes. While quantitative aspects of the immune system generally return to normal in the first 3 to 4 months, there is a prolonged delay in the recovery of qualitative immune functions. T-cell proliferation is impaired immediately after transplantation and recovers after more than 1 year. There is a documented defect in IL-2 producing cells post-BMT, but PHA-stimulated T cells are TAC+. Therefore, addition of IL-2 in vitro may normalize the T-cell proliferation defect. NK and LAK activities normalize very early post-BMT. In the light of these data, the clinical assessment of rIL-2 administration on the immunological reconstitution of ABMT patients and as consolidative immunotherapy is being investigated.
Cancer Treat Rev 1989 Jun
PMID:Immune reconstitution after bone-marrow transplantation. 267 Feb 11

Recovery of B-cell number and function was studied in 23 patients with hematological malignancies treated with high-dose chemoradiotherapy followed by autologous bone marrow transplantation (auto-BMT) in relation to the presence or absence of cytomegalovirus (CMV) infection. B cells recovered rapidly after auto-BMT and specific antibodies to herpes viruses remained nearly unchanged. Both were independent of the CMV status of the patients. However, the capacity of peripheral blood B cells to differentiate in vitro into cytoplasmic immunoglobulin (Ig)-positive cells (plasma cells) on pokeweed mitogen stimulation in the presence of normal T-cell help was significantly better in CMV-negative patients than in CMV-positive patients after auto-BMT, but was decreased in both groups. Serum Ig levels were, in contrast, higher in CMV-positive patients than in CMV-negative patients after auto-BMT.
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PMID:Influence of cytomegalovirus infection on the recovery of humoral immunity after autologous bone marrow transplantation. 304 Apr 53

Neurologic complications are extremely common after bone marrow transplantation and occur in well over half of all patients. Approximately 6 per cent of BMT recipients die as a direct result of neurologic problems. Metabolic encephalopathy, the most common clinical syndrome, is usually due to multiple organ failure. The second most common complication is CNS infection with fungi and viruses. Cerebrovascular disorders are the third most common neurologic problem, and most are related to underlying endocarditis (either infectious or nonbacterial thrombotic endocarditis). Less common neurologic complications include side effects of drugs, recurrence of malignancy, and treatment-induced leukoencephalopathy. Neurologic involvement due to GVHD appears to be limited to rare neuromuscular syndromes. No evidence of CNS involvement from GVHD has been detected.
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PMID:Neurologic complications of bone marrow transplantation. 304 47

Bone marrow transplantation is impossible without effective support with blood components during the period of pancytopenia before graft function appears. We analyzed 39 patients with leukemia and three patients with severe aplastic anemia with regard to the pre- and postgrafting requirements for RBC and PLT transfusions. Overall a median of eight RBC and four PLT concentrates were necessary in all 42 patients after allogeneic BMT (ranges, 1-32 RBC and 1-11 PLT units). Requirements were identical irrespective of the underlying disease (ALL, AML, CML, SAA). Transfusion need for RBC and PLT concentrates increased in patients over 30 years old and with a major red blood group AB0 barrier between marrow donor and recipient. The presence of grade II-IV GvHD increased RBC requirements significantly, but not PLT requirements. In addition these patients were dependent on RBC transfusions for significantly longer periods. Only one patient required therapeutic granulocyte transfusions. In a CMV-negative patient with a CMV-negative marrow donor, who died of veno-occlusive disease, cytomegalovirus was transmitted inadvertently by a seropositive PLT concentrate in his final course. Our transfusion strategy included frozen deglycerolized RBC concentrates and single donor PLT concentrates, collected mainly from the marrow donor by a cell separator. All blood products were irradiated in vitro with 1500 cGy before transfusion. An optimal transfusion policy starting before BMT can contribute to successful bone marrow transplantation.
Recent Results Cancer Res 1988
PMID:Hematological support in patients undergoing allogenetic bone marrow transplantation. 305 Dec 11

An artificial mixture of breast cancer cell line cells (T-47D) and normal human marrow cells was used to investigate optimal approaches for autologous BMT. The experiments were designed to test the applicability of chemocytotoxic agents, a dye-mediated photolytic agent and SBA for in vitro purging in autologous BMT of patients with advanced malignancies. Treatment with high concentration of etoposide (VP-16) (10 to 80 micrograms/ml) resulted in a maximal depletion of 1.5 log, whereas more efficient tumor cell eradication (2.5 log) was achieved by 30-min incubation with 100 micrograms/ml4HC. Photosensitization by exposure for 90 min to daylight in the presence of MC-540 could remove only 1 log of T-47D cells. The chemocytotoxic treatment with 4HC was chosen to follow initial tumor cell separation by SBA bound to polystyrene magnetic beads that had previously been shown to bind to several cancer cell types while sparing marrow progenitor cells. Artificial mixtures containing 10 to 14% T-47D cells in fresh normal BM cells were subjected to SBA-magnetic beads, and the SBA-negative fraction was further treated with 4HC. The combined two-step procedure resulted in a consistent tumor cell depletion of greater than 4 logs. The purging procedure appears acceptable for clinical marrow purging prior to cyropreservation and autotransplantation in patients with documented BM involvement of neoplastic cells sensitive to 4HC with positive binding to SBA such as breast cancer.
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PMID:Combination of magnetic and chemocytotoxic cancer cell depletion for autologous bone marrow transplantation. 306 Apr 42


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