Hepatic Venoocclusive Disease: A Major Complication of Hematopoietic Stem Cell Transplantation in Cancer Patients

DeLeve, Laurie D.

doi:10.1177/030089160108700224

Cited by 8 publications

(8 citation statements)

References 19 publications

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“…Yet, one major concern was high TRM caused by additive cytotoxicity of these two alkylators, which play an important role in the development of organ damage or hepatic VOD by depleting glutathione in hepatocytes contributing to cellular damage. [17][18][19] In particular, specific metabolites of cyclophosphamide are known to be associated with increased transplantation-induced mortality after conditioning, especially combined with busulfan. 1,20 Like cyclophosphamide, fludarabine also has a potent immunosuppressive effect without increasing toxicity of busulfan.…”

Section: Discussionmentioning

confidence: 99%

New myeloablative conditioning regimen with fludarabine and busulfan for allogeneic stem cell transplantation: comparison with BuCy2

Chae

et al. 2007

Bone Marrow Transplant

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A regimen of busulfan and cyclophosphamide (BuCy2) is regarded as the standard myeloablative regimen for SCT. This study evaluated the hypothesis that fludarabine can replace cyclophosphamide for myeloablative allogeneic SCT. Ninety-five patients underwent allogeneic SCT from HLA-identical donors, following BuCy2 (n ¼ 55) or busulfan þ fludarabine (BF, n ¼ 40). The efficacy of fludarabine compared to cyclophosphamide was retrospectively evaluated. The BF group exhibited a shorter duration until engraftment (P ¼ 0.001), lower incidence of acute and chronic GVHD (Po0.001 and P ¼ 0.003, respectively), and non-relapse mortality (NRM) (P ¼ 0.039). Furthermore, the event-free survival and overall survival were significantly higher for the BF group compared to the BuCy2 group (P ¼ 0.004 and 0.002, respectively). After adjusting for age, the risk status of disease, GVHD prophylaxis and donor type, the BF regimen was found to be an independent favorable risk factor for event-free survival (hazard ratio (HR), 0.181; 95% confidence interval, 0.045-0.720; P ¼ 0.016) and overall survival (HR, 0.168;; P ¼ 0.026). The replacement of cyclophosphamide with fludarabine for myeloablative conditioning seems to be more effective in terms of short-term NRM, and GVHD compared to BuCy2 regimen in allogeneic transplantation.

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Section: Discussionmentioning

confidence: 99%

New myeloablative conditioning regimen with fludarabine and busulfan for allogeneic stem cell transplantation: comparison with BuCy2

Chae

et al. 2007

Bone Marrow Transplant

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“…12 In GO-related VOD, sinusoidal obstruction and fibrosis are especially marked, and thus the term sinusoidal obstructive syndrome (or SOS) has been proposed for this variant, but the mechanism of GO's toxicity on the liver is yet to be elucidated. 3,17 Calicheamicin is a cytotoxic enediyene antibiotic. Once internalized in cells it binds to DNA in the minor groove, causing DNA double-strand breaks and cell death.…”

Section: Discussionmentioning

confidence: 99%

Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation

Wadleigh

Richardson

Zahrieh

et al. 2003

Blood

291

179

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“…6,7 Low glutathione (GSH) levels in hepatocytes (intrinsic or drug-induced) may contribute to such cellular damage. 8 Plasma levels of the cytoreductive agents commonly used in the conditioning regimen, busulfan (Bu) and cyclophosphamide (Cy) and/or its metabolites, have been associated with increased risk of HVOD. 9,10 The association between elevated Bu levels and HVOD has been attributed to Bu-mediated depletion of hepatic GSH, which in turn predisposes hepatocytes to injury from ensuing Cy exposure.…”

Section: Introductionmentioning

confidence: 99%

Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation

Srivastava

Balasubramanian

Shaji

et al. 2004

Blood

156

118

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Hepatic venoocclusive disease (HVOD) in bone marrow transplantation (BMT) is attributed to toxicity of cytoreductive agents, especially busulfan and cyclophosphamide, in the conditioning therapy. Busulfan, as well as the metabolites of cyclophosphamide, are conjugated with glutathione (GSH), catalyzed by enzymes of the glutathione S-transferase (GST) family. To assess the impact of polymorphisms of the GST genes, GSTM1 and GSTT1, on the risk of HVOD, we evaluated 114 consecutive patients with ␤-thalassemia major undergoing BMT. There was a significantly increased incidence of HVOD in patients with the GSTM1-null genotype compared with those with the GSTM1-positive genotype (46.5% vs 18.3%; P ‫؍‬ .001). Pharmacokinetic analysis in these patients showed that the clearance of busulfan was higher and first-dose steady-state concentration was lower among those with HVOD (0. 403

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Hepatic Venoocclusive Disease: A Major Complication of Hematopoietic Stem Cell Transplantation in Cancer Patients

Cited by 8 publications

References 19 publications

New myeloablative conditioning regimen with fludarabine and busulfan for allogeneic stem cell transplantation: comparison with BuCy2

New myeloablative conditioning regimen with fludarabine and busulfan for allogeneic stem cell transplantation: comparison with BuCy2

Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation

Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation

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