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)

A 25-year-old woman with AIDS was submitted to HLA-identical allogeneic BMT after cytoablation with busulphan and cyclophosphamide and combined anti-HIV-1 therapy with zidovudine, IFN-alpha 2 and anti-HIV-1-specific T cell clones. Marrow engraftment occurred after 18 days and tests for HIV-1 were negative after 30 days but the hematologic reconstitution of the patient was poor. A second BM infusion from the same donor was ineffective and treatment with GM-CSF only induced a transient increase of the blood cell count, suggesting iatrogenic damage to the BM microenvironment. The development of ARDS led to the death of the patient 10 months after transplantation. Post-mortem investigation did not reveal any active infections and PCR on autopsy tissues was negative for HIV-1.
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PMID:Allogeneic bone marrow transplantation combined with multiple anti-HIV-1 treatment in a case of AIDS. 813 53

A 29-year-old male patient presented with acute liver failure from non-A, non-B and non-C hepatitis, necessitating orthotopic liver transplantation. After operation he developed progressive pancytopenia on the basis of aplastic anemia, which was probably hepatitis associated. After therapy with GM-CSF had failed, he underwent allogeneic BMT from his HLA genotypically identical brother following a conditioning regimen of CY 50 mg/kg x 4 and 500 cGy total lymphoid irradiation. He engrafted promptly but transfusion dependency did not resolve until CMV viremia was treated with ganciclovir. The patient is alive and well 2 years after BMT.
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PMID:Successful allogeneic bone marrow transplantation in an adult with aplastic anemia following orthotopic liver transplantation for non-A, non-B, non-C hepatitis. 827 44

GM-CSF has been used successfully in autologous BMTs, and more recently in patients undergoing allogeneic BMT, for acute or chronic leukemia. We report two patients with hepatitis-related aplastic anemia who received recombinant human GM-CSF following HLA-identical sibling allogeneic BMTs. Both patients were conditioned with CY 200 mg/kg given over 4 days and received GM-CSF at 250 micrograms/m2 beginning 6 h after marrow infusion and continuing daily until the absolute neutrophil count was > 1.0 x 10(9)/l for 2 days. Both patients had prompt engraftment, achieving an absolute neutrophil count of > 0.5 x 10(9)/l on day 13. Neither patient had side-effects attributable to the GM-CSF although one patient developed severe acute GVHD after the cessation of GM-CSF therapy. Our experience suggests that GM-CSF can be safely used in aplastic anemia patients undergoing BMT and that GM-CSF may be useful to decrease the incidence of graft failure associated with less intensive conditioning regimens.
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PMID:Use of recombinant GM-CSF following allogeneic BMTs for aplastic anemia. 840 68

We evaluated patients presenting with large and recurrent sterile serosal effusions following bone marrow transplants. From a review of the Minnesota BMT Database from 1974 to 1993, seven patients with unexplained multiple effusions involving two or more of the pleural, pericardial or peritoneal cavities were identified. Patients with veno-occlusive disease (VOD), infections, cardiac insufficiency, tumor relapse and GM-CSF toxicity were excluded. All had onset following engraftment and six occurred before day 100. Unexplained multiple effusions were observed in recipients of allogeneic transplants but not autologous transplants and were found only in patients with acute and/or chronic GVHD. Five of seven patients also had cytomegalovirus (CMV) disease. Multiple effusions appear to be part of the presentation of severe acute or chronic GVHD, often in association with CMV disease in patients who receive allogeneic donor marrow.
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PMID:Unexplained effusions: association with allogeneic bone marrow transplantation and acute or chronic graft-versus-host disease. 1456

Hematopoietic growth factors like G-CSF or GM-CSF have been shown to shorten the period of severe neutropenia after HD chemotherapy and autologous BMT, and are now widely used to mobilize hemopoietic stem cells into peripheral blood. In order to evaluate the possibility of delaying G-CSF administration after transplantation of G-CSF mobilized blood stem cells (BSC), we randomized 35 cancer patients to receive CSF at day 1 (group 1, n = 19) or at day 6 (group 2, n = 16) after transplantation and here we present their hematological reconstitution. BSC collection was performed by apheresis after G-CSF priming for 5 or 6 days (600 micrograms daily subcutaneously). Hematological recovery is comparable between the two groups: a median of 10 (range 7-16) vs 11 (range 9-18) days to reach an ANC > 0.5 x 10(9)/1 in group 1 (G-CSF day 1 after transplant) vs group 2 (G-CSF day 6 after transplant, P = NS). Median time to reach an unsupported platelet count of 25 x 10(9)/1 was 14 days in the two groups (range 8-110 and 10-40 respectively, P = NS); patients received less G-CSF after transplantation in group 2. No difference appeared in terms of transfusion support, number of days of fever of i.v. antibiotic treatment. Patients' hospital stay was the same in the two groups. Our data suggest that delaying G-CSF administration after infusion of mobilized blood cells is not detrimental to hematological recovery, while it lowers the overall cost of the procedure.
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PMID:Administration of G-CSF can be delayed after transplantation of autologous G-CSF-primed blood stem cells: a randomized study. 872 50

Twenty-five patients with hematologic malignancies were treated with busulfan (16 mg/kg) and cyclophosphamide (50 mg/kg x 3 days) as conditioning for bone marrow transplantation using marrow from serologically matched, DR locus genotypically identical unrelated donors. Previous studies of BuCy2 as conditioning for UD-BMT have reported a graft failure rate of up to 21% suggesting it may be insufficiently immunosuppressive in this setting. We elected not to use BuCy4 as it may have a higher incidence of extramedullary toxicity. In addition the patients received GM-CSF (500 mg/m2) from day 0, cyclosporine and short-course methotrexate (15 mg/m2 x 1, then 10 mg/m2 x 3) as GVHD prophylaxis and prophylactic ganciclovir at engraftment if either they or their donor were CMV antibody positive. The median age of the 25 patients was 41 years and the most common diagnosis was CML (76%). Seven patients were considered poor risk and eight males were recipients of marrow from female donors. Sixteen patients survive at a median of 435 days from transplant. The actuarial overall and disease-free survivals at 1 year in this group of older patients were 62 +/- 20% and 57 +/- 20% and 100-day survival was 70%. The engraftment rate was 100%; there have been no instances of secondary graft failure. Fifteen patients (60%) developed grade II-IV GVHD and 12 of 16 (75%) developed some chronic GVHD but only half of these were extensive. The performance status of survivors is good (median of 90); seven of 12 eligible patients are back at work. This study demonstrates that UD-BMT can be successfully performed in very closely HLA-matched older patients using a chemotherapy-only protocol and that low rates of severe acute GVHD can be achieved without T cell depletion.
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PMID:Unrelated donor bone marrow transplantation without T cell depletion using a chemotherapy only condition regimen. Low incidence of failed engraftment and severe acute GVHD. 872 53

G-CSF and GM-CSF have been shown in each clinical setting to reduce the duration of neutropenia, with the exception of the scant data available in the unrelated bone marrow transplant setting. These growth factors also have been shown to have no leukemogenic effect during the observation periods of the trials discussed. In MDS, one major randomized trial has demonstrated a reduction in incidence of infection. This has not yet been demonstrated in AML and allogeneic BMT. Data from ongoing and future trials will be helpful in elucidating their effect on treatment-related morbidity and overall survival.
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PMID:Clinical use of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in neutropenia associated with malignancy. 881 4

Rejection after allogeneic BMT for aplastic anemia is a complication with a high risk of mortality. We describe a patient who, following a second episode of rejection after a second BMT entered a third durable remission subsequent to treatment with ALG, donor lymphocyte infusions, GM-CSF, and erythropoietin. Therapy was well tolerated. At 5 years after rejection treatment, his hematopoiesis is of complete donor origin as determined by analyses of short tandem repeats. Thus, donor lymphocyte infusions can be considered as a therapy option for marrow rejection after allogeneic BMT for aplastic anemia.
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PMID:Rejection of the second allogeneic graft in a patient with severe aplastic anemia reversed by antilymphocyte globulin and donor lymphocyte infusions. 897 92

Since the early 80s, the EORTC Leukemia Group has included 3947 patients in 8 consecutive phase III studies on acute myelogenous leukemia, with stratification according to the age groups. Some of these patients were included by other cooperative groups (GIMEMA, HOVON), within intergroup studies. The main hypotheses tested by randomization were intensive chemotherapy consolidation, allogeneic and autologous bone marrow transplantation in the younger patients. In patients aged 60 years or more, a wait and see policy followed by a palliative chemotherapy was compared to an immediate conventional induction treatment, mitoxantrone was compared to daunorubicin, and, during remission, a low dose Ara-C maintenance treatment to no maintenance. The main results can be summarized as follows: Allogeneic BMT, and, relatively, autologous BMT do better than intensive chemotherapy consolidation with regards to the disease-free survival, but not for the overall survival after remission. In the elderly, an immediate induction and a low-dose Ara-C maintenance treatment are preferable to the other options tested. Mainly in patients aged more than 45, the supplementary toxicity of more intensive chemotherapy consolidation, with high dose Ara-C, counter balanced the increased anti-leukemic effect. Finally the trials randomizing GM-CSF during induction yielded disappointing results. The EORTC LCG is currently studying the relative value of various intercalating agents during induction, and of the G-CSF as well, and, during remission the autologous peripheral stem cells compared to bone marrow transplantation.
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PMID:The EORTC trials for acute myelogenous leukemia. EORTC Leukemia Cooperative Group. European Organisation of Research and Treatment of Cancer. 897 88

Allograft recipients are often unwell with significant organ dysfunction by the time delayed or failed engraftment is diagnosed. We attempted to identify factors associated with graft failure, or death due to infection, hemorrhage or graft failure in 712 patients undergoing allogeneic BMT. Low leukocyte counts between days 12 and 22 were strongly associated with subsequent graft failure or death. In multivariate analysis, a leukocyte count of < or = 0.2 x 10(9)/l on day 16 was the most powerful predictor of graft failure or death. Transplants from HLA-mismatched and unrelated donors were also associated with increased risk of both, and T cell depletion with increased risk of graft failure. On the basis of these findings, it may be possible to define graft failure in functional terms as early as 2 weeks after BMT rather than at 3 or 4 weeks. The use of growth factors can then be limited to patients most likely to benefit from them, and it may be possible to salvage patients at risk of complications of low counts early before their clinical condition deteriorates. We suggest that patients with leukocyte counts of 0.2 x 10(9)/l or less 14-16 days after BMT should be started on G-CSF or GM-CSF even if they are clinically well, and consideration should be given to a second infusion of cells.
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PMID:Early identification of patients at risk of death due to infections, hemorrhage, or graft failure after allogeneic bone marrow transplantation on the basis of the leukocyte counts. 905 Dec 45


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