The syndrome of hepatic veno-occlusive disease after marrow transplantation

Abstract

The clinical syndrome of VOD is a frequent cause of nonrelapse mortality among patients receiving high-dose cytoreductive regimens. Patients likely to develop VOD have existing liver dysfunction, evidence of infection before conditioning, tend to receive more intensive preparative regimens, and often receive marrow from alternative donors. Therapeutic drug monitoring of busulfan and pharmacokinetic dose adjustments appear to be useful in reducing the incidence of VOD in patients receiving this agent. Data are contradictory as regards whether pharmacologic prophylaxis is effective. Patients who will develop severe VOD are characterized by a rapid increase in serum bilirubin as well as weight. Supportive management of these patients should attempt to preserve respiratory as well as renal function, sometimes a very difficult task. Treatment with recombinant tissue plasminogen activator has promise. However, given its potential for toxicity, a prospective randomized trial should be performed. Hopefully, as more data regarding the molecular and cellular mechanisms of this illness are elucidated, more thoughtful prevention strategies will be developed. This will be necessary, particularly as newer, more intensive preparative regimens are being developed, as access to alternative donors increases, and as more diseases will be treated with this approach.

Earlier defibrotide initiation post‐diagnosis of veno‐occlusive disease/sinusoidal obstruction syndrome improves Day +100 survival following haematopoietic stem cell transplantation

“…VOD/SOS develops via a progressive cascade of pathophysiological events that generate a prothrombotic-hypofibrinolytic state (Kumar et al, 2003;Palomo et al, 2010;Carreras & Diaz-Ricart, 2011;Richardson et al, 2013;Fan & Crawford, 2014). The initial toxic injury occurs to sinusoidal endothelial cells and hepatocytes in zone 3 of the liver acinus, causing endothelial cell activation, which in turn both triggers and supports an inflammatory response (Bearman, 1995;Carreras & Diaz-Ricart, 2011). The injured sinusoidal endothelial cells round up and slough off the endothelial wall, compromising its integrity, and permitting extravasation of blood into the space of Disse, which leads to thrombosis and extraluminal compression of the sinusoidal vessels (Carreras & Diaz-Ricart, 2011;Fan & Crawford, 2014).…”

Plasminogen activator inhibitor‐1 is an independent diagnostic marker as well as severity predictor of hepatic veno‐occlusive disease after allogeneic bone marrow transplantation in adults conditioned with busulphan and cyclophosphamide

“…Veno-occlusive disease (VOD) of the liver is a frequent and often fatal complication of bone marrow transplantation (BMT) (Baglin, 1994;Bearman, 1995). Endothelial damage, induced by high-dose chemoradiation therapy, is believed to be the key event in the pathogenesis of VOD (Bearman, 1995). Endothelial injury triggers the coagulation cascade, induces thrombosis of the hepatic venules, and eventually leads to fibrous obliteration of the affected venules (Shulman et al, 1987).…”

“…VOD occurs in up to 54% of patients who undergo BMT (Bearman, 1995). Published case-fatality rates for VOD after BMT vary widely from 0 to 67% (Bearman, 1995).…”

“…However, a diagnosis of VOD usually depends on clinical criteria because of a high frequency of false negative liver biopsy results (Shulman et al, 1980) and a risk of bleeding from a percutaneous liver biopsy in thrombocytopenic patients. Many disorders may mimic or be confused with VOD in the early period of BMT (Bearman, 1995;Carreras et al, 1998). Aside from serum bilirubin level, no laboratory parameter has been standardized as a diagnostic marker of VOD.…”

“…Aside from serum bilirubin level, no laboratory parameter has been standardized as a diagnostic marker of VOD. Furthermore, severity of VOD is defined retrospectively, based on the clinical outcome (Bearman, 1995). If any single parameter or combination of parameters can serve as diagnostic markers or severity predictors of VOD, they can be used as guidance for early therapeutic intervention.…”