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)

Disseminated fungal infection not infrequently complicates the course of allogeneic bone marrow transplantation (allo BMT) in severely immunocompromised patients, and the prognosis of BMT patients who develop systemic fungal infection is very poor. We describe a patient who developed disseminated Candida albicans infection with liver abscess after the first allo BMT for acute myelogenous leukemia (FAB M2). The infection was successfully eradicated by the administration of miconazole and amphotericin B. However, 1 year after the first allo BMT, the patient suffered a relapse of acute myelogenous leukemia with fungal liver abscess. A second allo BMT, accelerating granulocyte recovery by recombinant human granulocyte colony-stimulating factor (rhG-CSF), was successfully performed and the fungal liver abscess resolved with a combination therapy of fluconazole and amphotericin B. The patient is alive and free of both leukemia and fungal disease more than 37 months after the first allo BMT and 25 months after the second allo BMT.
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PMID:Successful second allogeneic bone marrow transplantation in a relapsed acute myeloid leukemia patient with fungal liver abscess. 138 22

Murine fibrosarcoma cell line BMT-11 was induced with 3-methylcholanthrene and maintained in culture. Transplantation of BMT-11 into syngeneic C57BL/6 mice produced leukocytosis consisting of marked increments of neutrophils and monocytes associated with massive splenomegaly. In order to elucidate the mechanisms of this leukemoid reaction, we studied the changes occurring in hematopoietic progenitor cells in BMT-11-transplanted mice. The numbers of granulocyte-macrophage colony-forming units (CFU-GM), erythroid colony-forming units (CFU-E), erythroid burst-forming units (BFU-E), and mixed colony-forming units (CFU-Mix) in the spleen showed dramatic 216-fold, 18-fold, 64-fold, and 80-fold increases, respectively, relative to the value in the control mice 5 weeks after the BMT-11 implantation. In contrast, the levels of progenitor cells in the bone marrow remained within normal limits. The nature of the colony-stimulating factor (CSF) secreted from BMT-11 tumor cells was also studied. BMT-11-conditioned medium (BMT-11-CM), BMT-11 tumor extract, and sera from the mice bearing transplanted BMT-11 tumor contained CSF that stimulated mainly granulocyte and macrophage lineages. Furthermore, the expression of the granulocyte colony-stimulating factor (G-CSF) gene in BMT-11 cells were detected by Northern blot analysis.
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PMID:Methylcholanthrene-induced murine fibrosarcoma cell line BMT-11 secretes granulocyte colony-stimulating factor. 170 45

The hemopoietic growth factor filgrastim (r-metHu G-CSF) stimulates granulopoiesis after autologous BMT and can also be used as a peripheral blood progenitor cell (PBPC)-mobilizing agent. Rapid platelet recovery follows the addition of filgrastim-mobilized PBPC to autologous BMT. We have now studied 29 adults with malignant lymphoma, Hodgkin's disease or ALL to assess the ability of filgrastim-mobilized PBPC to rapidly and durably restore hemopoiesis without bone marrow (BM) infusion. Patients with a high yield of PBPC from three leukaphereses, defined as > 30 x 10(4)/kg GM-CFC, were eligible for PBPC transplant without BM. Patients with a low yield of GM-CFC received both PBPC and BM infusion. After filgrastim therapy 12 or 24 micrograms/kg/day by continuous sc infusion for 6 or 7 days, a high yield was obtained in 11 of 29 patients. Kinetics of recovery of both the platelet and neutrophil counts were more rapid in the high yield group than in the low yield group. The platelet count recovered to > 20 x 10(9)/l at a median of 9 days, to > 50 x 10(9)/l at 11 days and the neutrophil count to > 0.5 x 10(9)/l at 9 days in the high yield group compared with 12 days, 37 days and 10 days, respectively, in the low yield group (p = 0.028, p < 0.001 and p = 0.027). Fewer platelet transfusions were required in the high yield group (median 11 vs 29.5 units, p = 0.021).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II study of autologous filgrastim (G-CSF)-mobilized peripheral blood progenitor cells to restore hemopoiesis after high-dose chemotherapy for lymphoid malignancies. 752 4

The role of flow cytometric reticulocyte (RET) counting and the immature RET fractions (IRF) in the evaluation of hematopoietic recovery following chemoradiotherapy-induced aplasia was studied. RET counts and IRF were studied using an automated flow cytometric reticulocyte counter (Sysmex R-2000) in three groups of patients: 58 patients undergoing an autologous bone marrow transplantation (ABMT group), 28 of whom received granulocyte colony-stimulating factor (G-CSF); 28 patients undergoing an allogeneic bone marrow transplantation (BMT group); and 28 patients receiving remission-induction chemotherapy for acute leukemia (CHEMO group). To evaluate the IRF the percentages of RET fractions with middle and high fluorescence reticulocyte (MFR and HFR, respectively) were used. A rising IRF (expressed as the percentage of MFR + HFR) was the first sign of hematopoietic recovery (ABMT group, IRF 9 days versus 18 days for the absolute neutrophil count (ANC); BMT group, 15 versus 18 days; CHEMO group, 9 versus 11 days). When recovery of the ANC (> 0.5 x 10(9)/l) was compared with that of the iRF (MFR + HFR > 5%), statistically significant differences were found in all three groups. Additionally, 93.1% of the ABMT, 92% of the BMT and 91.2% of the CHEMO recovered the IRF before the ANC. In conclusion, an elevation in the percentage of IRF is the first sign of hematologic recovery in the majority of patients receiving remission-induction chemotherapy and the first sign of engraftment in those submitted to ABMT or BMT. Serial automated flow cytometric quantitative reticulocyte counting provides a useful and early measure of erythropoiesis indicative of hematopoietic reconstitution or successful bone marrow engraftment following marrow transplantation.
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PMID:Flow cytometric reticulocyte quantification in the evaluation of hematologic recovery. Spanish Multicentric Study Group for Hematopoietic Recovery. 752 98

Recombinant granulocyte colony-stimulating factor (rhG-CSF) has been shown to hasten granulocyte recovery after autologous BMT. In current protocols, rhG-CSF treatment starts 1 day after BM reinfusion. Our study retrospectively examined the effects on haematological recovery of a day 6 delayed administration. Seventy-eight patients receiving autologous BMT for malignant lymphoma (21 non-Hodgkin's lymphoma and 9 Hodgkin's disease) or solid tumors (33 breast carcinoma and 5 ovarian carcinoma) were split up into three study groups. Two groups receiving a 5 micrograms/kg/day of rhG-CSF starting either 1 day (day +1 group, n = 25 patients) or 6 days (day +6 group, n = 24 patients) after BM reinfusion were compared with 29 historical control patients. Granulocyte recovery to 0.5 x 10(9)/l was 12 days in day +6 and day +1 groups versus 16 days in control group (p < 0.005) without any difference in other hematological parameters, infectious complications or length of hospitalisation between the three groups. The day +6 administration allows elimination of a median of 7 days rhG-CSF. It has been concluded that the day +6 administration gives the same clinical benefit as day +1 administration with consequent cost reductions.
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PMID:Delayed administration of granulocyte colony-stimulating factor after autologous bone marrow transplantation: effect on granulocyte recovery. 753 61

We determined L-selectin expression and elastase levels in neutrophils obtained from patients receiving granulocyte colony-stimulating factor (G-CSF) either alone (given for increasing peripheral progenitor cells for harvest) or in combination with high-dose chemotherapy with autologous bone transplantation support (BMT). Administration of G-CSF alone for 3-5 days produced a decrease in L-selectin expression in neutrophils (25 +/- 4 versus 7 +/- 1, mean +/- SEM; mean channel fluorescence, n = 10) with no effect on neutrophil elastase activity (3.1 +/- 0.3 versus 3.4 +/- 0.6; micrograms elastase/million cells; n = 9). In contrast, in patients in the BMT group the L-selectin expression was increased (26 +/- 2 versus 38 +/- 3; n = 20) and elastase activity was markedly decreased (2.9 +/- 0.2 versus 1.4 +/- 0.2, n = 12) compared with values before BMT. The changes in L-selectin expression correlated with the ability of neutrophils to adhere to human umbilical vein endothelial cells. The decrease in the neutrophil elastase activity was not associated with an increase in the plasma elastase/alpha 1-antitrypsin complex levels, indicating that the decrease in the neutrophil elastase activity is not caused by activation of neutrophils and release of the enzyme into the plasma. Administration of G-CSF alone did not cause a decrease in the neutrophil elastase activity but increased plasma elastase/alpha 1-antitrypsin complex levels. There was no change in CR3 expression on neutrophils under any of these conditions. These observations suggest that the changes seen in neutrophils during BMT are influenced by various factors associated with BMT other than the administered cytokine alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in L-selectin expression and elastase activity in neutrophils from patients receiving granulocyte colony-stimulating factor alone or in conjunction with high-dose chemotherapy with autologous bone marrow transplantation. 753 70

A multicentre, randomised vehicle-controlled single-blind dose ranging trial of intravenous recombinant granulocyte colony-stimulating factor (rhuG-CSF) administration after BMT has been performed in 121 patients with non-myeloid malignancies. All the doses of rhuG-CSF used (2-20 micrograms/kg/day) resulted in significant acceleration of neutrophil recovery, and a dose-response effect was apparent (p < 0.05). At the 20 micrograms/kg/day dose of rhuG-CSF the median time taken to achieve a neutrophil count of > 0.5 x 10(9)/1 was reduced from 19 to 13 days (p < 0.001) and the time to achieve a neutrophil count > 1.0 x 10(9)/1 on the first of 3 consecutive days, from 26 to 14 days (p < 0.001). There was a trend to less antibiotic use in the rhuG-CSF recipients and the median time in hospital was markedly reduced by 11-15 days (p < 0.01). There was no toxicity in this study attributable to rhuG-CSF.
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PMID:Randomised vehicle-controlled dose-finding study of glycosylated recombinant human granulocyte colony-stimulating factor after bone marrow transplantation. 768 52

Granulocyte colony-stimulating factor (G-CSF) has been shown to be effective in accelerating neutrophil recovery after BMT. In this single centre study, we have examined the effect of delaying the start of treatment with G-CSF (5 micrograms/kg) until 8 days after BM infusion in a cohort of 17 patients with malignant lymphomas undergoing autologous BMT. In comparison with historical controls, neutrophil recovery to > 0.5 x 10(9)/l was shortened from 22 to 14 days (p < 0.01). Patients receiving G-CSF required iv antibiotics for a median 13 days (control 17, p < 0.05) and were discharged a median 28 days post-ABMT (control 32.5, p = NS). Patients received G-CSF for a median of 10 days only. Although these results require confirmation in a randomised trial they suggest that G-CSF administration could be delayed until 8 days after BMT without compromising efficacy and with an accompanying reduction in treatment costs.
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PMID:Efficacy of delayed granulocyte colony-stimulating factor after autologous BMT. 768 2

The use of hematopoietic growth factors (HGFs) in the allogeneic transplant setting has sometimes been avoided for fear of stimulating leukemic cell growth and intensifying graft-vs.-host disease (GVHD). However, neither an increase in relapse rate nor an aggravation of GVHD has been routinely described when HGFs are used after allogeneic bone marrow transplantation (allo-BMT). Early outcomes after HLA-matched allo-BMT in 26 patients with hematologic malignancies treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) from the day of transplantation were analyzed. Results were compared to those from a series of 38 patients treated earlier with an identical approach, but not scheduled to receive HGFs after transplantation. All patients received a preparative regimen consisting of etoposide, cyclophosphamide, and total-body irradiation and GVHD prophylaxis with cyclosporine and a short course of methotrexate (MTX). The analysis has shown that the duration of neutropenia was significantly decreased in the group of patients treated routinely with HGFs (median 17 vs. 20 days; p < 0.001). These patients also required fewer days of intravenous antibiotic therapy (median 20 vs. 34 days; p < 0.001), had fewer positive blood and tissue cultures (median 2 vs. 12 and 13 vs. 28; p = 0.02 and p = 0.05, respectively), needed fewer packed red blood cell transfusions (median 7 vs. 11; p < 0.03), and were discharged earlier from the hospital (median 33.5 vs. 39 days; p < 0.001). The use of HGFs was not associated with an increase in acute GVHD or early leukemic relapse. No side effects were attributable to the simultaneous administration of MTX and HGF during the neutropenic period. A trend toward better 100-day actuarial survival for patients treated with rhG-CSF or rhGM-CSF did not reach statistical significance. A decrease in the number of early deaths from fungal or bacterial infections was found in the cytokine-treated group (p = 0.05). These data suggest that the early use of rhG-CSF or rhGM-CSF after HLA-matched allo-BMT in hematologic malignancies accelerates engraftment, reduces hospitalization time, and improves outcome, without increasing acute GVHD or early relapse. Because MTX-based prophylaxis regimens are associated with prolonged neutropenia, the routine use of HGFs after transplantation may be particularly useful in regimens including MTX.
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PMID:Hematopoietic growth factors after HLA-identical allogeneic bone marrow transplantation in patients treated with methotrexate-containing graft-vs.-host disease prophylaxis. 854 38

The successful use of granulocyte transfusions in a patient undergoing volunteer unrelated donor BMT for very severe aplastic anemia complicated by presumed fungal infection is described. Granulocytes were obtained by leukapheresis of normal volunteer donors stimulated by granulocyte colony-stimulating factor. The yields of granulocytes obtained by this method were sufficient to produce sustained neutrophil increments in the recipient throughout the transplant course. In vitro studies indicated that granulocytes were functionally normal, a finding which was supported clinically by the rapid resolution of infection, even in the setting of immunosuppression post-transplantation. This demonstrated the potential value of granulocyte transfusions in high-risk BMT.
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PMID:Multiple granulocyte transfusions facilitating successful unrelated bone marrow transplantation in a patient with very severe aplastic anemia complicated by suspected fungal infection. 854 74


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