Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the efficacies of serum catalase (CAT), 5'-nucleotidase (5'NT), and tumor necrosis factor-alpha (TNF) as diagnostic markers of acute graft-vs-host disease (GVHD) in 28 allogeneic bone marrow transplant recipients by comparing their abilities to discriminate between GVHD-related and non-GVHD-related complications. Mean peak serum CAT concentrations for patients with GVHD-related complications (n = 17) were about fivefold higher than concentrations in patients with non-GVHD-related complications (n = 25; P = 0.003), whereas the mean peak concentrations of serum 5'NT and TNF were not substantially different. Similarly, the sensitivity and specificity of serum CAT (100% and 88%, respectively) for use as a diagnostic marker of GVHD were much better than those of serum 5'NT (88% and 24%, respectively) or serum TNF (65% and 4%, respectively). Receiver-operating characteristic plots of all possible sensitivity-specificity pairs obtained over the whole range of results also showed that serum CAT has the best diagnostic accuracy. Low specificities of serum TNF and 5'NT were caused mainly by their increase in septicemia, fungal infection, and veno-occlusive disease and after the use of granulocyte-macrophage colony-stimulating factor to stimulate donor cell engraftment. Serum CAT may prove to be a rapid and relatively noninvasive test for the diagnosis of acute GVHD.
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PMID:Serum catalase as marker of graft-vs-host disease in allogeneic bone marrow transplant recipients: pilot study. 758 45

Autologous bone marrow transplantation (AuBMT) is an accepted treatment modality for patients with high-risk or relapsed hematological malignancies. Hepatotoxicity, in particular veno-occlusive disease (VOD), is a significant complication of this therapy. The purpose of this study was to determine the clinical relevance of abnormal liver function in the patients who received high-dose cytotoxic therapy and AuBMT for hematological malignancies at Memorial Sloan Kettering Cancer Center. Medical records of 180 consecutive patients between 1984 and 1991 treated with cytotoxic chemotherapy and AuBMT for acute myelogenous leukemia, non-Hodgkin's lymphoma, and Hodgkin's disease were reviewed. Forty-six patients (26%) developed jaundice with bilirubin > 4 mg/dl. These patients had a 43% toxic death rate compared to an 11% toxic death rate in patients with lower bilirubins (p < 0.001). The main etiology of hyperbilirubinemia was VOD of the liver noted in 22 of the 180 patients (12%). Other etiologies of jaundice included hepatitis, sepsis with multiorgan dysfunction, cholecystitis, and recurrent disease. Hyperbilirubinemia of various etiologies is a significant complication of AuBMT. Several new strategies are under investigation to decrease the toxicity of intensive therapy.
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PMID:Abnormal liver function in patients undergoing autologous bone marrow transplantation for hematological malignancies. 762 20

The outcomes of 39 patients with hematological disorders who had undergone allogeneic bone marrow transplantation (BMT) from September 1986 to March 1992 were reported. The length of follow-up was six to 50 months. Twenty patients with acute leukemia, eight patients with aplastic anemia, seven patients with chronic myelogenous leukemia, two patients with non-Hodgkin's lymphoma, and two patients with myelodysplastic syndrome were included. Major complications were acute graft-versus-host disease (GVHD) (17 cases out of 36 evaluable cases; 47 percent), chronic GVHD (13/25; 52 percent), sepsis (20/41; 49 percent), interstitial pneumonitis (IP) (10/30; 33 percent), and veno-occlusive disease (VOD) of the liver (5/41; 12 percent). Acute and chronic GVHD were well managed with cyclosporin, methotrexate, and steroids. VOD of the liver seemed to be associated with the pretransplant regimen including busulfan and cyclophosphamide. The overall probability of disease free survival of 39 patients who had undergone allogeneic BMT was 0.56. This includes nine high risk cases such as HLA antigen mismatch between the donor and the recipient, and as in the second or subsequent remission or in relapsed cases. The probability of disease free survival in patients with acute leukemia, chronic myelogenous leukemia, and aplastic anemia including high risk cases was 0.55 (n = 20), 0.71 (n = 7), and 0.50 (n = 8) respectively. These results indicate that allogeneic BMT is the major therapeutic strategy for patients whose survival could not be expected by conventional chemotherapy and that drug intensification for conditioning regimen is also important.
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PMID:Allogeneic bone marrow transplantation as a therapeutic modality for hematological disorders: a report based on 39 cases. 786 58

Between October 1988 and December 1992, 167 patients with leukemia receiving marrow transplants from HLA-identical donors and conditioned with cyclophosphamide (120 mg/kg) were randomized to additional treatment with either busulfan (16 mg/kg, n = 88) or total body irradiation (TBI; n = 79). The busulfan-treated patients had an increased cumulative incidence of veno-occlusive disease of the liver, ie, 12% compared with 1% in the TBI group (P = .009). Furthermore, hemorrhagic cystitis occurred in 24% of the busulfan patients versus 8% in the TBI patients (P = .003). In patients with advanced disease beyond first remission or first chronic phase, transplantation-related mortality was 62% among the busulfan-treated patients compared with 12% among the TBI recipients (P = .002). These differences between the two groups were statistically significant in multivariate analysis. Seizures were seen in 6% of the busulfan-treated patients and were absent in the TBI group (P = .03). Grade II-IV of acute graft-versus-host disease (GVHD) was similar in the two groups, but grade III-IV and chronic disease was more common in the busulfan-treated group (P = .04). Death associated with GVHD occurred in 17% of the busulfan-treated group and 2% of the TBI group (P = .003). Patients treated with busulfan had a 3-year actuarial survival of 62%, which was worse than the 76% among those treated with TBI (P < .03). In multivariate analysis, poor survival was associated with advanced disease (P < .0001), no posttransplant septicemia (P = .0006), grade II-IV GVHD (P = .006), and busulfan treatment (P < .02). The incidence of relapse did not differ between the two groups. Relapse-free survival was also similar in the two treatment groups on analysis of data from all patients, children, patients with early disease, and those with acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia. However, in adults (P = .05) and patients with advanced disease (P = .005), leukemia-free survival was significantly better in those treated with TBI. We conclude that patients treated with busulfan have more early toxicity and an increased transplant-related mortality in patients with advanced disease. TBI is therefore the treatment of choice, especially in adults and patients with advanced disease. However, busulfan is an acceptable alternative for patients with early disease and for those in whom TBI is not feasible.
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PMID:A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group. 816 51

To assess the prevalence, risk factors, clinical causes and outcome of acute renal failure (ARF) following bone marrow transplantation (BMT), a retrospective analysis of 275 patients was undertaken. ARF was diagnosed in 72 patients (26%) and occurred in 81.9% within the first month. The three main clinical causes were multifactorial (36%), nephrotoxic (29%), and veno-occlusive disease of the liver (VOD) 15%. The prevalence was higher in allogeneic BMT (36%) than in autologous BMT (6.5%). Risk factors related to the development of ARF wee preexisting VOD and age older than 25 years. Logistic regression in allogeneic BMT confirmed this association (VOD, odds ratio 3.8; age offer than 25, odds ratio 1.9). Underlying disease, graft-versus-host disease, sepsis, conditioning therapy, and sex were not associated with ARF. Seventeen cases of ARF required hemodialysis (24%) mainly in association with VOD (70.5%). The overall morality from ARF was 45.8%, the dialyzed group having the highest mortality (88%). Survival in the ARF group was continuously worse up to 3 months and the actuarial survival at 10 years was 29.7 versus 53.2%. We conclude that ARF is a common complication mainly in allogeneic BMT and carries a grave prognosis. VOD and age were risk factors for ARF.
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PMID:Acute renal failure in patients following bone marrow transplantation: prevalence, risk factors and outcome. 854 68

Peripheral blood progenitor cell (PBPC) autografts have a number of advantages over autologous bone marrow transplantation (ABMT) as haematopoietic support after high-dose chemotherapy in patients with breast cancer. These may include less contamination by tumour cells, reduced morbidity and mortality and additional dose escalation of chemotherapy. A dose-escalation study is described using recombinant granulocyte colony-stimulating factor (G-CSF; filgrastim) primed PBPC support and post-infusion filgrastim for patients with high-risk or metastatic breast cancer. The regimen involved the use of cyclophosphamide, thiotepa and carboplatin at five dose levels. The main problem to emerge was organ toxicity induced by chemotherapy or sepsis. Patients receiving higher levels of chemotherapy were therefore allocated or not to an additional regimen involving pentoxifylline, ciprofloxacin and dexamethasone in an attempt to inhibit tumour necrosis factor alpha (TNF-alpha) which is believed to be one of the principal mediators of chemotherapy-related organ toxicity. The incidence of bilirubin elevations, weight gain > 5% and veno-occlusive disease (VOD) was lower in patients receiving the 'anti-TNF' therapy. The simultaneous use of PBPC support and 'anti-TNF' therapy therefore allows a substantial increase in chemotherapy dosage. Further studies with larger patient numbers are required to show whether this decreased toxicity also produces increased patient survival.
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PMID:High-dose chemotherapy for breast cancer: clinical advantages of autologous peripheral blood progenitor cells (PBPC) compared with autologous bone marrow transplantation (ABMT). 875 Jan 43

We investigated the nature of hemostatic alterations occurring after bone marrow transplantation. In 45 patients, we evaluated the coagulation parameters, naturally occurring anticoagulants and thrombomodulin at days +15 and +22 after conditioning therapy. It was observed that endothelial cell damage is a central pathogenetic mechanism in some BMT complications. The increased plasma level of thrombomodulin after conditioning therapy is therefore discussed as a marker of endothelial cell injury. At day +15 a significant increase of fibrinogen from 276.1 mg/dI to 389.1 mg/dI was observed, while the natural anticoagulants all decreased significantly. Eleven patients with clinical complications related to endothelial damage had a significant thrombomodulin increase which, in uncomplicated patients, remained unchanged or resulted in lower than baseline values. Analysis of the data shows a strong correlation between clinical findings, reflecting endothelial cell injury and thrombomodulin increase when the increment is > or = 30%. We found a significant elevation in thrombomodulin in 70% of clinical complications related to endothelial cell damage namely: septicemia, GVHD, VOD. There were four cases (or 9%) of false positive data, and only two (or 4.5%) of false negative results. We therefore propose thrombomodulin assessment as a valid parameter to monitor chemotherapy toxicity-related complications.
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PMID:Increased plasma level of vascular endothelial glycoprotein thrombomodulin as an early indicator of endothelial damage in bone marrow transplantation. 886 50

Autologous and allogeneic bone marrow grafting both require cytoreductive therapy but only the allogeneic procedure requires immunosuppressive agents. Allogeneic bone marrow transplantation has been reported to be associated with a high incidence of both renal failure and veno-occlusive disease (VOD) of the liver, the combination of which is associated with a high morbidity and mortality. There is less known about the frequency and severity of these complications in patients undergoing autologous bone marrow transplantation. In the present study renal, hepatic and other complications were examined in 232 patients with Stages II/III and IV breast cancer who were treated with high-dose chemotherapy and autologous hematopoietic cell support with either marrow or peripheral blood progenitor cells. The post-treatment severity of the renal dysfunction was classified as follows: Grade 0, normal renal function [< 25% decrement in glomerular filtration rate (GFR)]; Grade 1. mild renal dysfunction (> 25% decrement in GFR but < a twofold increase in serum creatinine); Grade 2, > twofold rise in serum creatinine but no need for dialysis; Grade 3 > than twofold rise in serum creatinine and need for dialysis. There were 102 patients (44%) who were classified as Grade 0 and 81 patients (35%) who were classified as Grade 1 renal dysfunction. Severe renal dysfunction (Grades 2 and 3) was observed in 49 of the 232 patients (21%). This severe renal dysfunction of 21% compares with a previously reported 53% incidence of severe renal dysfunction for allogeneic bone marrow transplantation. Similarly, the frequency of hepatic VOD was less (4.7% or 11 of 232 patients) in this autologous bone marrow transplant study as compared to a reported incidence of hepatic VOD ranging from 22 to 53% in large series of allogeneic bone marrow transplant patients. The severe renal dysfunction (Grades 2 and 3) in the present autologous hematopoietic cell support study correlated most significantly with sepsis, liver and pulmonary dysfunction. The major fall in GFR occurred during chemotherapy but before hematopoietic cell support, thus primarily incriminating the cytoreductive therapy rather than the hematopoietic cell support. The only significant effect of different chemotherapy protocols was, at four weeks, the Taxol-treated group had a significantly lower creatinine clearance as compared to the BCNU treated group.
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PMID:Renal function in high dose chemotherapy and autologous hematopoietic cell support treatment for breast cancer. 887 80

Cilastatin, an inhibitor of the tubular brush border enzyme dehydropeptidase-I, is added in a fixed combination to imipenem. Cilastatin has been demonstrated in different animal models and in one clinical trial, to reduce the nephrotoxicity associated with cyclosporin A. To evaluate a possible nephroprotective effect of cilastatin following allogeneic BMT we conducted a retrospective analysis of 104 patients transplanted in our BMT Unit from January 1991 to January 1995. Imipenem/cilastatin (I/C) was used in a non-randomized manner in 64 patients during this period. Acute renal failure (ARF) was diagnosed in 32 patients (30%). ARF was not associated with gender, sepsis, conditioning regimen, underlying disease, bilirubin, or age. VOD occurred in 12/32 (37.5%) of patients with ARF whereas it occurred in only 7/72 (9.7%) of patients without ARF (P < 0.0007). ARF was not correlated with use of aminoglycosides, vancomycin, ciprofloxacine, ceftazidime or amphotericin-B. However, 13 patients of 64 exposed to I/C (20.3%) developed ARF vs 19 of 40 patients (47.5%) who were not exposed to I/C (P < 0.003; OR 0.28). Stratified analysis and multiple logistic regression confirmed the I/C nephroprotective action. The mean cyclosporin A levels in the I/C group were significantly decreased (208.6 +/- 64.9) vs the non-I/C group (265 +/- 118). We conclude that these results suggest I/C may counteract acute cyclosporin A nephrotoxicity following BMT and further prospective clinical trials are needed to confirm if routine administration of cilastatine confers benefit in the BMT setting.
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PMID:Nephroprotective effect of cilastatin in allogeneic bone marrow transplantation. Results from a retrospective analysis. 889 92

Successful allogeneic peripheral blood progenitor cell (PBPC) transplantation has recently been reported by several transplant centers. This is a first report describing allogeneic PBPC transplantation in five patients using related pediatric donors between the ages of 4 and 13 years. Donors underwent 3 or 4 days of rhG-CSF treatment (6 micrograms/kg q 12 h) for stem cell peripheralization prior to PBPC collection, which was performed by continuous-flow apheresis on day 4 or 5. Venous access was exclusively by ante-cubital veins. A median of 2.2 times (range 1.4-3.6) the donor's total blood volume (TBV) was processed per procedure. In cases where the donor's TBV was < 2 liters, the blood cell separator was primed with human serum albumin (HSA-5%), and anticoagulation was performed using a combination of heparin (pre-apheresis bolus + continuous infusion (CI)) and/or ACD-A (CI at a reduced rate). The median number of CD34+ cells collected per kg of donor body weight (b.w.) and per liter of donor blood processed during each procedure was 128 x 10(4) (range 58 x 10(4)-314 x 10(4)). Between one and two aphereses were sufficient to collect a safe CD34+ cell engraftment dose of 3 or 4 x 10(6)/kg of recipient b.w. Two PBPC recipients were parents, and three were siblings. After freezing and thawing, the median number of CD34+ cells per kg of recipient b.w. thawed and transfused was 8.5 x 10(6) (range 3.2 x 10(6)-9.7 x 10(6)). The time to PMN > 1000/microliters was between 10 and 16 days (four out of five evaluable patients), and platelets > 20000/microliters were reached between day 13 and 14 post-transplantation (three out of five evaluable patients). Two out of three evaluable patients developed grades one and three acute GVHD, and one out of three developed chronic GVHD. Two patients died of sepsis and VOD at day 10 and 19, respectively. Two adult patients are alive and in cytogenetic and molecular remission of CML at +339 and +227 days post-allotransplantation. One 3-year-old girl with hemophagocytic lymphohistiocytosis is in remission at +304 days post-transplantation. Using pediatric donors for allogeneic PBPC transplantation appears to be safe, yields a sufficient amount of progenitors for prompt engraftment, and results in clinical outcome similar to adult PBPC allotransplantation.
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PMID:Allogeneic peripheral blood stem cell transplantation using normal patient-related pediatric donors. 893 41


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