Use of plasma exchange for the treatment of hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) after reduced intensity conditioning allogeneic stem cell transplantation

Abstract

Hepatic veno-occlusive disease/sinusoidal obstructive syndrome (VOD/SOS) is a severe regimen-related complication of allogeneic stem cell transplantation that occurs in 10% to 60% of recipients and is characterized by a high mortality. Until recently, the therapeutic management of hepatic VOD/SOS has relied on the use of a wide spectrum of pharmacologic agents which include: heparin, ursodiol, prostaglandins and pentoxifylline, albeit with limited success. In recent years the description of promising results regarding the use of defibrotide for the prevention and management of moderate to severe hepatic VOD/SOS has been shown. However, the use of this pharmacologic agent is still under clinical investigation and not available for patients living outside of the trial-sponsoring countries. Here we describe the successful treatment of a case of severe hepatic VOD/SOS by means of plasma exchange, a procedure that is thought to alleviate liver failure by eliminating inflammatory cytokines and pro-coagulant substances circulating in the peripheral blood of affected patients. The patient was a 53 year old male undergoing allogeneic haematopoietic stem cell transplantation from a related, HLA-matched (10/10) donor due to chronic prolymphocytic leukaemia. The patient was subjected to a reduced intensity conditioning (RIC) regimen (TBI + fludarabine + ATG) and received methylprednisolone alone as GvHD prophylaxis. The patient developed clinical hepatic VOD/SOS on day +7 characterized by increased total serum bilirubin levels at the expense of direct bilirubin (reaching 25 mg/dL in less than 36 hours), jaundice, ascites, upper-quadrant pain, hepatomegaly, respiratory distress and hepatic encephalopathy, soon after the patient developed renal failure. The patient was subjected to three 3-liter plasma exchange sessions on separate days starting on day +8. On day +10, alanine amino transferase, lactic dehydrogenase and bilirubin levels achieved their maximum (1306 IU/L, 3597 IU/L and 35 mg/dL, respectively). By day +15 the bilirubins and most liver enzymes had regained their normal levels. The patient subsequently developed progressive multifocal leukoencephalopathy that culminated in the patient’s death on day +49. Our analysis allows us to conclude that hepatic VOD/SOS is an important complication of reduced intensity conditioning regimens that can be managed and overcome by an easily accessible therapeutical approach such as plasma exchange.