Use of Vitamin E and Glutamine in the Successful Treatment of Severe Veno‐Occlusive Disease Following Bone Marrow Transplantation

Nattakom, Thomas V.; Charlton, Angela; Wilmore, Douglas W.

doi:10.1177/011542659501000116

Cited by 35 publications

(23 citation statements)

References 14 publications

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“…12 One previous case report has shown successful treatment of long-standing severe VOD in a patient not responding to either conventional therapy or tPA. 7 In this case, l-glutamine (20 g daily) was given orally, for more than a month, whereas in our patients a short course of 8 and 10 days was given intravenously. Although in the two cases the VOD was not confirmed by liver biopsy, we believe that the diagnosis was firmly made by the combination of classical clinical signs with typical U/S Doppler studies.…”

Section: Discussionmentioning

confidence: 74%

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Glutamine and vitamin E in the treatment of hepatic veno-occlusive disease following high-dose chemotherapy

Goringe

Brown

O’Callaghan

et al. 1998

Bone Marrow Transplant

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Summary:Hepatic veno-occlusive disease (VOD) of the liver is a common complication following high-dose cytotoxic therapy for bone marrow transplantation (BMT). Liver injury is believed to occur following free radical damage to endothelial cells of the sinusoids and small hepatic veins. Glutathione the main antioxidant of the cytosol becomes depleted following chemotherapy. Animal studies have shown that glutamine infusions can maintain glutathione levels and protect against free radical injury. We present two cases of established VOD successfully treated with intravenous glutamine (as dipeptide) and oral vitamin E. Although both cases have possible confounding factors we believe that these give support to the notion that glutamine/vitamin E may have a role in the prophylaxis and treatment of VOD. Further formal trials are indicated. Keywords: veno-occlusive disease; glutamine; vitamin E; bone marrow transplantation Hepatic veno-occlusive disease (VOD) is a leading cause of morbidity and mortality following chemoirradiation therapy for bone marrow transplantation (BMT).1,2 Typically occurring within 10-20 days of the start of high-dose treatment, it presents as a triad of painful hepatomegaly, jaundice and fluid retention. Liver biopsies characteristically show subendothelial swelling, narrowing of central veins, dilatation and engorgement of sinusoids, closure of sinusoidal fenestrae and necrosis of hepatocytes in zone 3 of the acinus. A mechanism which may result in this pattern of damage is depletion of glutathione (GSH) allowing hepatocyte and/or endothelial cell injury. The centrilobular zone is relatively depleted of GSH and is the site of glutathione-dependent detoxifying enzymes. Agents used in conditioning regimes can cause GSH depletion, eg BCNU, TBI and bulsulphan, Currently treatment of VOD has largely consisted of supportive measures designed to maintain intravascular volume and decrease interstitial oedema. Other treatments used with various measures of success have included recombinant tissue plasminogen activator (tPA), heparin, prostaglandin E, ursodeoxycholic acid and pentoxifylline. Despite these treatments the outcome remains fairly dismal, with no clear role for tPA where mortality still occurs in 20-50% of cases. Therefore, interest is turning to methods of maintaining high glutathione levels (the main antioxidant of hepatic cytosol). Glutamine becomes the rate limiting factor in hepatocyte production of glutathione during periods of catabolic stress. Standard intravenous hyperalimentation regimes do not provide glutamine supplementation; the amino acid itself is unstable in solution and this has led to the recent development of dipeptides such as glycyl-lglutamine and alanyl-l-glutamine which are stable in solution and are hydrolyzed rapidly to l-glutamine.Recently, dipeptiven (Fresenius, Runcorn, UK) which is a 20% solution of the dipeptide alanyl-l-glutamine, has become available. There is some suggestion that the addition of vitamin E is also helpful in combination with glutamine.7 Havi...

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Section: Discussionmentioning

confidence: 74%

“…There is some suggestion that the addition of vitamin E is also helpful in combination with glutamine. 7 Having observed no cases of VOD in a previous BMT study, 8 we decided to treat established VOD with the combination of alanyl-l-glutamine and vitamin E.…”

mentioning

confidence: 99%

Glutamine and vitamin E in the treatment of hepatic veno-occlusive disease following high-dose chemotherapy

Goringe

Brown

O’Callaghan

et al. 1998

Bone Marrow Transplant

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“…However severe adverse effects limits its routine use. There are anecdotal reports on the successful use of charcoal hemofiltration [77] , N-acetylcysteine [78] and glutamine/vitamin E [79,80] . Defibrotide, the most promising dr ug currently available for the treatment of VOD, is a single-stranded polydeoxyribonucleotide with anti-ischemic, anti-thrombotic and thrombolytic properties.…”

Section: Treatmentmentioning

confidence: 99%

Hepatic venous outflow obstruction: Three similar syndromes

Bayraktar

Seren²,

Bayraktar³

2007

WJG

116

110

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Our goal is to provide a detailed review of venoocclusive disease (VOD), Budd-Chiari syndrome (BCS), and congestive hepatopathy (CH), all of which results in hepatic venous outflow obstruction. This is the first article in which all three syndromes have been reviewed, enabling the reader to compare the characteristics of these disorders. The histological findings in VOD, BCS, and CH are almost identical: sinusoidal congestion and cell necrosis mostly in perivenular areas of hepatic acini which eventually leads to bridging fibrosis between adjacent central veins. Tender hepatomegaly with jaundice and ascites is common to all three conditions. However, the clinical presentation depends mostly on the extent and rapidity of the outflow obstruction. Although the etiology and treatment are completely different in VOD, BCS, and CH; the similarities in clinical manifestations and liver histology may suggest a common mechanism of hepatic injury and adaptation in response to increased sinusoidal pressure.

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“…[1][2][3][4] To date, no medical therapy has proven effective for the treatment of veno-occlusive disease. [5][6][7][8][9][10][11][12][13][14][15] Even with a recent shift to a low-intensity conditioning regimen (e.g., fludarabinecontaining regimens), veno-occlusive disease continues to be a concern. [16][17][18][19] Preventive strategies to decrease hepatic sinusoidal injury and subsequent thrombosis have not been convincing.…”

Section: Introductionmentioning

confidence: 99%

Use of prophylactic anticoagulation and the risk of hepatic veno-occlusive disease in patients undergoing hematopoietic stem cell transplantation: a systematic review and meta-analysis

Imran

Tleyjeh

Zirakzadeh

et al. 2006

Bone Marrow Transplant

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Hepatic veno-occlusive disease is a serious regimenrelated toxicity in patients undergoing hematopoietic stem cell transplantation. We performed a systematic review and meta-analysis of the literature on the effect of anticoagulation in preventing veno-occlusive disease. Several databases and online journals were searched for randomized controlled trials and cohort studies. Twelve studies (2782 patients) were eligible. Anticoagulation prophylaxis was associated with a statistically nonsignificant decrease in risk of veno-occlusive disease (pooled relative risk (RR), 0.90; 95% confidence interval (CI), 0.62-1.29). Results of one of three randomized controlled trials may have been affected by delayed introduction of anticoagulation. A second trial enrolled patients who received conventional chemoradiotherapy for early-stage disease (RR, 0.18; 95% CI, 0.04-0.78). The third trial was a pilot study with a small sample size (RR, 0.74; 95% CI, 0.53-1.04). Significant heterogeneity and methodologic weaknesses preclude drawing a meaningful conclusion from the pooled analysis. Despite some limitations, results of two of three eligible randomized controlled trials suggest that prophylactic anticoagulation may help prevent veno-occlusive disease. However, a large randomized controlled trial is needed for confirmation. Additionally, in future studies, owing to the wide spectrum of severity of veno-occlusive disease, outcomes such as 100-day mortality should strongly be considered.

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Use of Vitamin E and Glutamine in the Successful Treatment of Severe Veno‐Occlusive Disease Following Bone Marrow Transplantation

Cited by 35 publications

References 14 publications

Glutamine and vitamin E in the treatment of hepatic veno-occlusive disease following high-dose chemotherapy

Glutamine and vitamin E in the treatment of hepatic veno-occlusive disease following high-dose chemotherapy

Hepatic venous outflow obstruction: Three similar syndromes

Use of prophylactic anticoagulation and the risk of hepatic veno-occlusive disease in patients undergoing hematopoietic stem cell transplantation: a systematic review and meta-analysis

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