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)

Growth factor administration to donors prior to bone marrow (BM) harvesting results in an enrichment of the graft for myeloid precursors. In animals, growth factor-primed BM has a higher repopulating ability than untreated BM. Ten patients received an HLA-identical sibling, allogeneic transplant using granulocyte colony-stimulating factor (G-CSF)-stimulated BM. Stimulation consisted of G-CSF at 10 microg/kg/day for 2 days prior to harvest. Patients were transplanted for various benign and malignant hematological conditions. The GVHD prophylaxis consisted of cyclosporine, methotrexate and/or prednisone. Compared to untreated historical control BM, stimulated BM infusions contained similar number of nucleated cells (mean +/- s.d.: 3.5 +/- 1.5 vs 4.0 +/- 0.9 x 10(8)/kg), CD34+ cells (mean +/- s.d.: 7.5 +/- 3.0 vs 9.4 +/- 6.7 x 10(6)/kg), and CD3+ cells (mean +/- s.d.: 129 +/- 30 vs 190 +/- 59 x 10(6)/kg) but higher numbers of granulocyte-macrophage colony-forming units (mean +/- s.d.: 20 +/- 12 vs 96 +/- 34 x 10(4)/kg). Patients receiving stimulated BM had prompt and stable engraftment of white cells and platelets. On average they attained an ANC of > or = 1 x 10(9)/l 9 days earlier and a platelet count of > or = 20 x 10(9)/l 6 days earlier than historical controls receiving unstimulated HLA-identical sibling BM. Hospitalization was shortened by a mean of 10 days and transfusion requirements were modest. None of the patients developed severe GVHD or disease relapse. Two patients died of severe VOD post-BMT and thus were unevaluable for platelet engraftment. A third patient died of TTP on day 76 post-BMT. Seven patients are alive and well 49-585 days post-BMT. Stimulated BM may provide a valuable alternative to allogeneic BM and PBSC transplants. Ideal stimulation regimens need to be investigated.
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PMID:A pilot study of allogeneic bone marrow transplantation using related donors stimulated with G-CSF. 946 75

TNF-alpha (Tumor necrosis factor-alpha) is involved in many immunological and inflammatory processes, and might be expected to play an important role in the development of BMT-related complications. Triple therapy (pentoxifylline, ciprofloxacin and prednisone) with known anti-TNF activity was tested in 37 patients undergoing a hematopoietic progenitor transplant (HPT). A control group of 16 patients with similar characteristics was selected among consecutive patients receiving a HTP in a neighboring center who did not receive anti-TNF prophylaxis. Major transplant-related complications were registered (VOD, acute GVHD, infectious episodes, renal failure and mucositis) and survival status. TNF plasma concentrations were determined by ELISA, and pentoxifylline plasma concentrations were determined by HPLC. Among patients treated with pentoxifylline (PTX), ciprofloxacin and steroids, no difference in the mean survival time was observed compared with the control group. The incidence of procedure-related death up to day +35 was 11% in the study group and 6% in the control group. In spite of a tendency to a lower incidence of mucositis there was a higher incidence of infections (positive blood cultures) in the study group (49%) than in the control group (16.7%) (P = 0.16). This difference achieved statistical significance in patients receiving an allogeneic HPT (P = 0.05). It is likely that the use of steroids in the early period after transplant increases infectious episodes and makes control of GVHD difficult. The combined administration of steroids with pentoxifylline and ciprofloxacin has not proved beneficial in preventing mucositis, renal failure, VOD or GVHD, or in improving patient survival.
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PMID:Pentoxifylline, ciprofloxacin and prednisone failed to prevent transplant-related toxicities in bone marrow transplant recipients and were associated with an increased incidence of infectious complications. 946 81

Timing of transplantation in the chronic phase of chronic myeloid leukemia (CML) and previous treatment with interferon remains controversial. We have tried to discover what influence pretreatment with interferon alpha (IFN-A) has on the results of allogeneic bone marrow transplantation for CML patients treated in a single institution. Fifty-one consecutive patients with chronic phase Ph-positive CML who received an allogeneic bone marrow transplantation from a HLA-identical familial donor were evaluated. Thirty had been treated with IFN-A (IFN+ group) prior to BMT and twenty-one had not (IFN- group). Both groups were homogeneous for clinical characteristics such as age, sex, previous chemotherapy, disease status, and time from diagnosis to transplant. No difference was found in neutrophil and platelet count recovery between the IFN+ and IFN- group. The incidence of acute and chronic GVHD, VOD and severe mucositis was not significantly different. Relapse and both overall survival and DFS were similar for both groups. No adverse effects of prior IFN exposure on the outcome of HLA-identical sibling donor BMT for chronic phase CML patients were found in this study.
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PMID:Absence of influence of prior treatment with interferon on the outcome of allogeneic bone marrow transplantation for chronic myeloid leukemia. 967 95

Abnormal liver function before allogeneic BMT has been associated with VOD. Hepatitis G virus/GB virus C (HGV) is a recently discovered virus suggested to be a cause of non-A, non-B, non-C, non-D and non-E hepatitis. The aim of this retrospective study was to analyze the risk for liver complications and time to engraftment in patients infected with HGV. Fifty patients transplanted in 1995 were examined with RT-PCR for HGV on samples collected before, and between 3 and 6 months after BMT. Seven patients had HGV detected before BMT. No patient became infected during or early after the BMT. There were no differences in either pre- or post-transplant liver function abnormalities, VOD, or time to neutrophil engraftment in patients who did or did not have HGV detected before BMT. We conclude that the importance of HGV infection for the development of post-transplant complications is limited.
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PMID:Detection of hepatitis G virus/GB virus C after allogeneic bone marrow transplantation. 973 75

Factors that enhance hypercoagulability following BMT may have a pathogenetic role in VOD. To investigate the relevance of hemostatic parameters for the development of VOD, we prospectively measured protein C, protein S, antithrombin III (AT III), von Willebrand factor, and factor VIII in 50 consecutive patients undergoing allogeneic BMT. Each parameter was determined before conditioning, on day 0 of BMT and weekly for 3 weeks, and patients were monitored prospectively for the occurrence of VOD. VOD occurred in 26 patients at median post-BMT day 8.5 (range, day -2 to 17). Thirteen patients had mild, 10 had moderate and three had severe VOD. No coagulation parameters were significantly different at the baseline or on day 0 of BMT between patients with no/mild VOD and moderate to severe VOD. On day 7 and thereafter, levels of protein C and AT III were significantly lower in patients with moderate to severe VOD when compared to patients with no/mild VOD. Levels of protein C and AT III decreased before the clinical onset of VOD in patients with moderate to severe VOD. Early post-BMT reduction of these parameters may indicate the development of moderate to severe VOD.
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PMID:Relevance of proteins C and S, antithrombin III, von Willebrand factor, and factor VIII for the development of hepatic veno-occlusive disease in patients undergoing allogeneic bone marrow transplantation: a prospective study. 982 16

High-dose busulphan is an important component of many BMT conditioning regimens. High-dose busulphan therapy is associated with an increased risk of acute toxicity such as CNS toxicity and veno-occlusive disease (VOD). The toxicity was reported to correlate with a high AUC (area under the curve) during therapy. An intravenous form of busulphan would overcome the problems caused by inter-individual variability and bioavailability of busulphan and most probably minimize the problems with dose adjustment during therapy. The liposomal form of busulphan is an attractive alternative for intravenous administration of busulphan. In the present study, we compared the myeloablative effect of liposomal busulphan (LB) with that of the oral administration form and busulphan dissolved in organic solvent (Bus/DMSO) in mice. The pharmacokinetics of LB and Bus/DMSO were described by one compartment model while the oral data were fitted to one compartment model with first order absorption. The bioavailability of LB was 0.86+/-0.02 compared to that obtained after the oral administration (0.40-0.74). Myelosuppression was determined using the colony-forming unit granulocyte-macrophage assay (CFU-GM) on days 1, 3, 6 and 9 after the conditioning regimen. LB resulted in significant myelosuppression from day 1 to day 9. The decrease in CFU-GM after conditioning regimen with LB was not significantly different from that observed after oral busulphan. Moreover, the administration of liposomes only to the mice did not affect the bone marrow. No side-effects of the liposomal formulation were observed. We suggest that the novel form of busulphan is a promising drug for clinical use.
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PMID:Liposomal busulphan: bioavailability and effect on bone marrow in mice. 982 21

One hundred and forty children with hematologic malignancies undergoing allogeneic BMT were reviewed in order to clarify the incidence, onset time, and risk factors for veno-occlusive disease (VOD) of the liver. Thirty-eight patients (27.1%) developed VOD diagnosed according to the Seattle clinical criteria. Seventeen patients developed VOD within 20 days of transplantation (early-onset) and in 21 patients developed after day 20 (late-onset) including eight patients with histological confirmation. Late-onset VOD occurred from day 21 to day 508 (median day 39). Moderate or severe VOD developed in 11 early-onset and 13 late-onset patients. Death occurred in eight early-onset and 10 late-onset patients. Serum albumin and cholinesterase levels prior to the start of pretransplant conditioning were significantly lower in early-onset VOD than in late-onset VOD. Multivariate analysis showed that low serum albumin levels (< or =3.7 g/dl) prior to the start of pretransplant conditioning was most strongly associated with the development of VOD. Donor mismatch (other than HLA-matched relatives), use of minocycline, and a long interval (> or =13 months) between diagnosis and BMT were also significantly associated with the development of VOD. In contrast, use of fosfomycin was associated with a decreased risk. Our data suggest that hepatic function reserve is important in the development and onset time of VOD. Veno-occlusive disease of the liver is a complication which may occur a long time after transplantation.
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PMID:Veno-occlusive disease of the liver after allogeneic bone marrow transplantation in children with hematologic malignancies: incidence, onset time and risk factors. 989 23

Allogeneic BMT is treatment of choice for acute leukaemias(AL) and chronic granulocytic leukaemia (CGL). In the period form 1989 till 1997 36 allogeneic BMT have been performed for patients with AML, ALL and CGL using HLA matched related donors in University Medical Centre Ljubljana. The procedure was successful in 80% of patients with CGL and in 50% of patients with AL. The most frequent cause of death in CGL patients was CMV pneumonitis, relapse in patients transplanted for ALL, while in patients transplanted for AML beside relapse we observed four deaths due to complications of BMT ( acute GVHD, VOD, thrombotic thrombocytopenic purpura, liver failure due to hepatitis).
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PMID:Allogeneic BMT for acute leukemia and chronic granulocytic leukemia in University Medical Centre Ljubljana-Slovenia. 991 41

A 30-year-old woman developed veno-occlusive disease of the liver during an allogeneic BMT for acute leukemia. Treatment with recombinant human tissue plasminogen activator and heparin resulted in an incomplete and transient response followed by progressive disease. The patient was then given defibrotide (DF), a mammalian tissue-derived polydeoxyribonucleotide developed for the treatment of a number of vascular disorders, which has thrombolytic and anti-thrombotic properties. No significant bleeding or other major toxicities were observed during treatment and she made a full recovery. At 6 months after the onset of VOD her liver function tests and color flow Doppler ultrasound scan are normal. Our experience supports the preliminary results already obtained with DF. Its efficacy should be evaluated in a prospective randomized fashion.
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PMID:Defibrotide as salvage therapy for refractory veno-occlusive disease of the liver complicating allogeneic bone marrow transplantation. 1023 Nov 51

Interleukin 10 (IL-10) is a potent inhibitor of proliferative T cell responses toward alloantigens, and suppresses the production of pro-inflammatory cytokines which are important in cellular activation and recruitment to sites of inflammation. Because of these properties, we hypothesized that high IL-10 production in patients prior to BMT may predict a better outcome. To investigate this, peripheral blood mononuclear cells (PBMNC) were obtained from 58 recipients (11 autologous, 25 related donor (RD), and 22 unrelated donor (URD)), prior to conditioning therapy. PBMNC were cultured for 24 h in the presence and absence of lipopolysaccharide (LPS) and culture supernatants were assayed for IL-10 using an ELISA method. Spontaneously produced and LPS-stimulated IL-10 levels were correlated with the development of transplant-related complications (TRC) including grade II-IV acute GVHD, veno-occlusive disease, idiopathic pneumonia syndrome and multi-organ dysfunction syndrome, and with death before day 100. For the autologous group, there were no TRC and only one death prior to day 100; therefore, no statistical comparisons to IL-10 levels could be made. In the RD group, 36% developed one or more TRC and 24% died before day 100; however, there were no statistically significant associations between spontaneous or LPS-induced IL-10 levels. In URD patients 41% developed TRC and 55% died prior to day 100. In this group, higher levels of spontaneous IL-10 production were associated with a lower overall occurrence of TRC (P = 0.03) and early death (P = 0.04). Our data would indicate that higher levels of IL-10 production prior to URD BMT may predict fewer TRC, as well as early deaths. The hypothesis that high IL-10 production prior to BMT may decrease complications following URD BMT warrants further testing.
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PMID:High spontaneous IL-10 production in unrelated bone marrow transplant recipients is associated with fewer transplant-related complications and early deaths. 1038 51


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