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)

In clinical practice p-creatinine is used to estimate changes of GFR. Generally, it is believed that recovery of p-creatinine within 10% of initial baseline allows exclusion of relevant nephrotoxic changes. We evaluated whether recovery of GFR after discontinuation of CyA therapy can be adequately predicted by measuring p-creatinine alone. Fifty-four allogenic BMT patients were followed up by p-creatinine and classical inulin clearance (GFR) before BMT and 1, 3, 6, 12, 18, 24 months after BMT. A total of 10 patients fulfilled following three criteria: (1) 24 months total follow-up time; (2) at least 12 months follow-up after discontinuation of CyA therapy (3) no trimethoprim or cimetidine comedication at time of clearance measurement. Time after CyA withdrawal varied between 13 and 21 months (mean +/- standard deviation, 17 +/- 2 months); mean duration of CyA therapy was 8 +/- 2 months (minimum: 3 months, maximum: 11 months). After at least 12 months of CyA stop mean p-creatinine returned to baseline values. In contrast, mean GFR remained about 20% below baseline (paired sample Wilcoxon-test P < .02). Neither creatinine excretion nor body weight nor creatinine clearance changed significantly between baseline and 24 months after BMT. Follow-up of p-creatinine after CyA stop can overestimate the recovery of GFR. A 20% loss of GFR may remain unrecognized. We speculate that this phenomenon is due to tubular hypertrophy in the recovery phase.
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PMID:Plasma creatinine for the evaluation of recovery of glomerular filtration rate after discontinuation of cyclosporine A in bone marrow transplantation: results of a prospective study. 794 Aug 4

Patients with haematological malignancies undergoing allogeneic BMT were randomised to treatment with recombinant human erythropoietin (rHuEPO) (n = 25) or placebo (n = 25). rHuEPO was given at 200 U/kg daily for 4 weeks and 200 U/kg twice weekly for a further 4 weeks. The groups were similar regarding several prognostic factors. There were no differences between the two groups regarding time to engraftment, fever, hospitalisation, GVHD, infections, haemorrhages, transplant-related mortality, relapse and survival. However, more patients in the control group had a raised serum creatinine (43% vs 14%; p = 0.04). Red blood cell (RBC) transfusion requirements for the first 2 months after BMT were significantly lower in the rHuEPO group compared with the control group (5 units vs 10; p = 0.04). Time to unsupported Hb > 70 g/l was less in patients treated with rHuEPO (14 days vs 24; p = 0.03). No effect was seen on platelet engraftment or the number of transfused platelet units. Two patients in the control group compared with none in the rHuEPO group became refractory to platelet transfusions. According to the protocol the study drug was reduced (Hb > 100) or discontinued (Hb > 120) for a mean of 3.6 weeks among 11 rHuEPO patients compared with 1.9 weeks among 7 controls (p = 0.02). Seven of the treated patients compared with none of the controls reached Hb > 120 during the study period (p = 0.004). Among the rHuEPO treated patients, EPO-levels were significantly higher than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced blood transfusions requirements after allogeneic bone marrow transplantation: results of a randomised, double-blind study with high-dose erythropoietin. 801 63

Based on encouraging results of a recently published study on the clinical usefulness of oral pentoxifylline (PTX) to reduce transplant-related toxicities, prophylactic pentoxifylline was administered to 31 consecutive allogeneic BMT recipients with hematological malignancies. Patients received PTX as a continuous infusion at increasing dose levels (0.50, 0.75, 1.00 and 1.25 mg/kg/h) starting 1 day prior to the conditioning regimen. At all dose levels, PTX was well tolerated with no significant side-effects. When compared with a historical control group of 61 consecutively transplanted allogeneic BMT recipients, PTX patients did not appear to experience less gastrointestinal (moderate and severe mucositis: 100% vs 68%, p < 0.001), hepatic (hyperbilirubinemia > 1.5 mg/dl: 84% vs 30%, p < 0.001) or renal (creatinine > 1.5 mg/dl: 16% vs 27%, NS) toxicity or to have a lower incidence of GVHD > or = grade III (21% vs 22%, NS). Using i.v. PTX, we were unable to reproduce the reduction in morbidity and mortality in patients undergoing BMT which has been described for prophylactic oral PTX.
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PMID:Intravenous pentoxifylline failed to prevent transplant-related toxicities in allogeneic bone marrow transplant recipients. 827 35

During the first month after bone marrow transplantation, approximately 15% of patients develop acute renal failure (ARF). This usually occurs in the setting of hepatic veno-occlusive disease (VOD). Prior clinical data have suggested that this form of ARF has a hemodynamic basis, analogous to the hepatorenal syndrome (HRS). If so, then proximal tubular injury would not be expected. To directly test this hypothesis, enzymuria (N-acetyl-beta-D-glucosaminidase [NAG]) was quantitated in the following groups of patients within the first 35 days after BMT: (1) VOD+ARF (serum creatinine level > 1.5 mg/dL; N = 10); (2) VOD with relatively normal renal function (serum creatinine level < 1.5 mg/dL; N = 11); and (3) patients without hepatic or renal complications (BMT controls; N = 12). For comparison, NAG was also quantitated in the following groups of non-BMT patients: (1) toxic/ischemic acute tubular necrosis (ATN) (N = 10); (2) jaundice without azotemia (N = 5); and (3) HRS (N = 6). Urine samples from eight healthy subjects established normal NAG concentrations (2.5 +/- 0.5 microU/mg urinary creatinine; mean +/- SE). All non-BMT patients with ATN had markedly elevated NAG levels (61 +/- 12; P < 0.001), validating the test as a marker of tubular damage. NAG concentrations were significantly elevated in all of the control BMT patients (24 +/- 3; P < 0.01), and the presence of VOD was associated with further striking increments (approximately 50 times normal). However, the degree of enzymuria was virtually identical for VOD patients with (125 +/- 27) and without (122 +/- 17) ARF. Jaundice in a non-BMT setting was associated with only mild NAG elevations (11 +/- 2). However, striking enzymuria was noted in all HRS patients (61 +/- 20), equaling the levels seen with ATN. The following conclusions were derived: (1) subclinical tubular injury, as defined by enzymuria, appears to be ubiquitous after BMT; (2) VOD dramatically increases the extent of enzymuria; (3) the degree of enzymuria in VOD patients is not correlated with renal dysfunction, implying that the associated ARF has a large hemodynamic component; and (4) HRS and ATN manifest comparable degrees of enzymuria, suggesting that substantial tubular damage exists in both of these forms of ARF.
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PMID:Marked enzymuria after bone marrow transplantation: a correlate of veno-occlusive disease-induced "hepatorenal syndrome". 874 94

Fifteen allogeneic BMT patients in a phase II study were given foscarnet 60 mg/kg twice daily for 14 days as pre-emptive therapy against CMV disease. CMV infection was diagnosed by a leukocyte-based nested PCR. All 15 patients were evaluable for toxicity. One patient did not fulfill the inclusion criteria of two consecutively positive CMV PCR tests and therefore was not evaluable for efficacy. Thus, 14 of 15 patients were evaluable for development of CMV disease. None of the patients developed CMV disease and all 14 assessable patients had a negative CMV isolation at the end of therapy. None of the 15 patients had to discontinue therapy due to toxicity. Six patients reported mild gastrointestinal disturbances, three patients headaches, and three patients mild urethritis or hemorrhagic cystitis. Serum-electrolyte disturbances were common including abnormal magnesium, potassium and calcium levels. Two patients developed mild serum-creatinine increases requiring adjustment of the foscarnet dosage according to protocol. We conclude that a dosage of foscarnet of 60 mg/kg given twice daily seems to be safe and effective in preventing CMV disease in allogeneic BMT recipients. A study comparing foscarnet and ganciclovir is indicated.
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PMID:Foscarnet for pre-emptive therapy of CMV infection detected by a leukocyte-based nested PCR in allogeneic bone marrow transplant patients. 887 18

In a retrospective analysis, 79 allogeneic bone marrow recipients treated with AmBisome prophylactically or because of proven or suspected invasive fungal infection (IFI) were evaluated in 92 episodes. The median duration of treatment was 14 (range 1-112) days. The mean maximum dose given was 1.64 +/- 0.8 mg kg-1 day-1 and the mean total dose was 1.29 +/- 2.28 g. The overall incidence of reported adverse events was 194, of which none had a serious outcome. In six cases, the drug was withdrawn as a result of toxic or allergic reactions: dyspnoea and flush (3), urticaria (1), cholecystitis (1) and disorientation (one case, probably not related to AmBisome). No anaphylactoid reactions were seen. Laboratory findings, including low serum potassium (48% of the episodes), increased serum creatinine (38%) and increased serum sodium levels (7%), caused no major clinical problems. Thirteen cases of verified IFI were evaluated regarding the efficacy of AmBisome. Survival or cure of the mycotic infection occurred in 5/13 patients (38%). Two patients were treated with AmBisome (3.6 and 3.3 mg kg-1 day-1) because of verified IFI before BMT. One died of IFI. The other died of venoocclusive disease of the liver (VOD) without histological evidence of active IFI. We found a significant (P < 0.05) reduction in autopsy-proven IFI, 12/199 (6%) compared to the period when only conventional doses of amphotericin B were used, 26/227 (11%).
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PMID:Safety and efficacy of liposomal amphotericin B in allogeneic bone marrow transplant recipients. 890 28

Endothelial damage is thought to be a contributing factor in the pathogenesis of Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndromes (TTP/HUS). The present studies measured two markers of endothelial cell stimulation and/or activation [von Willebrand Factor (vWF:Ag) and thrombomodulin (TM)] in patients with TTP/HUS disorders and compared them to controls. The patient groups consisted of adults with TTP/HUS, with (n = 13) and without (n = 14) peak Cr levels >2.0 mg/dl. Additionally, 52 patients with Bone Marrow Transplant-associated Thrombotic Microangiopathy (BMT-TM) following allogeneic BMT were evaluated. Both vWF:Ag and TM were elevated in all patient groups compared to controls. TTP/HUS patients with peak Cr >2.0 mg/dl had higher TM levels (P < 0.001) than did those with peak Cr levels below 2 mg/dl. However, thrombomodulin/ creatinine (TM/Cr) ratios did not differ in these two groups nor did they differ from controls. BMT-TM pts had higher vWF:Ag levels and higher TM/Cr ratios than controls and TTP/ HUS, P < 0.001. The median TM/Cr ratio in BMT-TM was 91 (range = 34-229) compared to 38 (range = 29-50) in controls, P < 0.001 and 38 (range = 6 to 156) in TTP/HUS, P < 0.001. Additionally both TM (P < 0.001) and TM/Cr (P < 0.02) were higher in patients with Grades 3 and 4 BMT-TM compared to those with Grade 2 BMT-TM. These results suggest that endothelial cell activation occurs in TTP/HUS and BMT-TM. Since TM/Cr ratios were higher in BMT-TM compared to TTP/HUS, these findings suggest that the mechanism of elevated TM in BMT-TM cannot be explained solely by altered renal excretion. Taken together, these findings strongly indicate a role of endothelial cell damage in BMT-TM.
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PMID:Plasma von Willebrand Factor Antigen (vWF:AG) and thrombomodulin (TM) levels in Adult Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndromes (TTP/HUS) and bone marrow transplant-associated thrombotic microangiopathy (BMT-TM). 894 57

Nocardiosis has rarely been described after BMT. When the doses of immunosuppressive therapy were tapered, a 46-year-old BMT recipient developed chronic graft-versus-host disease (GVHD) and immunosuppresive drugs were increased. Sixteen days later the patient developed nocardiosis diagnosed by lung biopsy. Trimethoprim/sulfamethoxazole (TMP/SMZ) was initiated but the doses were reduced because of rising creatinine levels. Skin and cerebral dissemination of nocardiosis was observed and TMP/SMZ doses were increased. After 4 months, the brain lesion was unaltered despite resolution of pulmonary lesions. Clinical improvement was observed after drainage of the brain abscess.
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PMID:Clinical features and successful recovery from disseminated nocardiosis after BMT. 901 36

The knowledge of renal function in the course of BMT is poor. We prospectively investigated glomerular and tubular function in 42 children who underwent BMT because of malignancy. Seventeen children were transplanted autologously. Investigations were performed before and immediately after the conditioning regimen. Inulin and creatinine clearance, albuminuria, urine excretion of alpha 1-microglobulin, beta-N-acetylglucosaminidase, alanine-aminopeptidase, intestinal alkaline phosphatase, and Tamm-Horsfall-Protein as well as sodium- and phosphatreabsorption were measured. The patients were classified regarding use of total body irradiation (tTBI) in the conditioning regimen. BEFORE CR: Glomerular filtration rate (GFR) was not influenced by the underlying diagnosis or previous treatment. Mean GFR was elevated compared with the reference group. Microalbuminuria was elevated in 15% of patients, and mean levels were higher than in the reference group. Proximal tubular dysfunction was indicated by an elevated excretion of alpha 1-MG in 54%, of beta-NAG in 66%, of AAP in 40%, and of IAP in 47%. Fractional sodium excretion was abnormal in 21%, phosphate reabsorption in 5% and THP-excretion in 7% of the patients. AFTER CR: Creatinine clearance was not affected by CR. After CR alpha 1-MG, beta-NAG, FENa, AAP, and IAP were increased compared with values before CR. TP/Clcr was decreased. Excretion of THP was not altered by CR. In patients without fTBI there was a greater increase in alpha 1-MG excretion and decrease in phosphate reabsorption after CR compared with patients conditioned with fTBI. We conclude that significant proximal tubular dysfunction is present in about 50-60% of patients before and in nearly all alter CR. Distal tubular function was less severely affected. Severity of nephrotoxicity after CR did not correlate with pre-existing abnormalities.
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PMID:Renal function after conditioning therapy for bone marrow transplantation in childhood. 907 24

The use of conventional amphotericin B is limited by toxicity, side-effects, drug interactions and the need for large infusion volumes, especially for infants. Use of liposomal amphotericin B (AmBisome) in 15 paediatric BMT patients with primary immunodeficiency (PID) was therefore studied. Adverse clinical reactions to AmBisome and biochemical profiles were monitored daily for 2 weeks before, during and after each treatment episode. Fungal cultures were obtained weekly and when patients were pyrexial. There were 18 treatment episodes. Mean daily dose was 5 mg/kg (2-6 mg/kg). Mean duration of treatment was 25 days (5-90 days). Clinical reactions to AmBisome were observed in one infant who had a pyrexia of 38 degrees C. One of the 15 infants had a significant increase in creatinine level while on concomitant nephrotoxic therapy. Four developed mild hypokalaemia on AmBisome which resolved with increased potassium supplementation. AmBisome was well tolerated and without significant renal or hepatic toxicity in severely ill immunodeficient infants receiving multiple nephrotoxic and hepatotoxic drugs such as cyclosporin, vancomycin and foscarnet.
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PMID:Liposomal amphotericin (AmBisome) is safe in bone marrow transplantation for primary immunodeficiency. 920 17


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