Avoiding hepatic veno-occlusive disease: what do we know and where are we going?

Abstract

Summary:Hepatic venocclusive disease (V0D) is a common toxicity associated with myeloablative chemotherapy or chemoradiotherapy used to prepare patients for stem cell transplantation. A sizable proportion of patients who develop VOD die. It is clear that injury to endothelial cells and hepatocytes in zone 3 of the liver acinus is the initial event in the pathogenesis of VOD. What are less clear are the mechanisms of injury and whether this knowledge can be exploited. This manuscript will briefly review some recent data and discuss how that information has influenced clinical practice. Bone Marrow Transplantation (2001) 27, 1113-1120. Keywords: veno-occlusive disease; stem cell transplantation; toxicity VOD is characterized by a syndrome of jaundice, fluid retention and painful hepatomegaly and occurs in up to half of patients who receive ablative preparative therapy. 1 As many as half of patients with VOD die, usually of multiorgan failure. Signs of VOD usually present around the day of transplant, 2 although well described 'late onset VOD' has been reported. 3,4 Fluid retention and hepatomegaly are usually the first manifestations and typically present on or around the day of transplant. Jaundice develops later, around day 6. 2 The rate of rise in bilirubin and weight is also faster for patients whose illness is likely to be severe vs those who are likely to have self-limited disease. Furthermore, fewer than 20% of patients with mild VOD and 48% with severe VOD develop ascites. 2 These observations led to the development of a model p ϭ 1/(1 ϩ e Ϫz ) which would predict which patients with VOD were likely to die. 5 In this model, z ϭ ␤ 0 ϩ ␤ 1 (in total serum bilirubin) ϩ ␤ 2 (percent weight gain). The intercepts ␤ 0 , ␤ 1 and ␤ 2 change as day relative to transplant increases. 5 For

Successful treatment of hepatic veno-occlusive disease after myeloablative allogeneic hematopoietic stem cell transplantation by early administration of a short course of methylprednisolone

“…3,10,11 The course of VOD ranges from a mild reversible one to a severe syndrome associated with multiorgan failure. [1][2][3][4] Treatment is usually supportive, as approximately half of the patients with uncomplicated VOD ultimately recover spontaneously. 12 The precise sequence of events leading to the development of VOD is unknown.…”

“…[1][2][3][4] VOD is an important regimen-related toxicity observed after hematopoietic stem cell transplant (HSCT). [1][2][3][4][5][6][7][8][9] VOD is usually diagnosed based on clinical findings.…”

“…[1][2][3][4] VOD is an important regimen-related toxicity observed after hematopoietic stem cell transplant (HSCT). [1][2][3][4][5][6][7][8][9] VOD is usually diagnosed based on clinical findings. 3,10,11 Patients who meet all the criteria for VOD but have confounding causes of liver dysfunction, or meet only one of the criteria for VOD (jaundice or fluid retention), are considered to have liver dysfunction of uncertain etiology.…”

In children and adolescents, the pharmacodynamics of high-dose busulfan is dependent on the second alkylating agent used in the combined regimen (melphalan or thiotepa)

“…6,7 In addition, we have shown that busulfanthiotepa (BU TTP) is an effective salvage therapy for relapsed medulloblastoma in children. 8,9 Hepatic veno-occlusive disease (HVOD) 10,11 is the most severe and frequent extrahematological toxicity associated with high-dose busulfan in both adults and children. 12,13 Over the last 15 years, tremendous efforts have been expended to evaluate whether drug monitoring and dose adjustment could reduce the incidence and severity of busulfan-containing high-dose chemotherapy.…”

Enfermedad veno-oclusiva hepática, colitis ulcerosa idiopática y trombosis portal: Comunicación de un caso clínico

“…El tratamiento de la EVOH propiamente tal es complejo y están en estudio marcadores que ayuden a un diagnóstico precoz, junto a un manejo de mayor eficacia antitrombótica con el uso de tPA, antitrombina III o defibrotide 18 . Se ha ensayado el manejo profiláctico con ácido ursodeoxicólico, heparina continua y de bajo peso molecular en los pacientes que requieren trasplante alogénico de médula ósea 19,20 . En nuestro paciente, el tratamiento anticoagulante estándar fue motivado precozmente por la trombosis portomesentérica e indujo una evolución favorable del compromiso postsinusoidal, probablemente en relación a la estasia con microtrombosis que se describió histológicamente a ese nivel, mostrando el hígado con volumen y flujo más normal, sin hipertensión portal al 5º mes.…”