Late onset veno-occlusive disease following high-dose chemotherapy and stem cell transplantation

Abstract

Summary:The original definition of hepatic veno-occlusive disease (VOD), which is still widely accepted, includes onset of the clinical syndrome before day +20 following highdose chemotherapy (HDC) and stem cell transplantation (SCT). We retrospectively identified four patients following HDC and SCT presenting with late onset VOD occurring at day +24, day +27, day +34 and day +42 post SCT. All patients had moderate VOD, with successful resolution of the VOD before day +100 with optimal supportive therapy. Common risk factors for VOD shared by all four patients included an older age (median age: 60 years), and use of a busulphan-containing regimen. Mean and maximum bilirubin levels for all patients during the VOD syndrome were 2.02, 1.76, 5.09, 2.87 mg/dl and 2.5, 2.2, 8.9 and 4.1 mg/dl, respectively, which correlated well with duration of VOD. All patients encountered platelet transfusion-dependent thrombocytopenia during VOD. Ursodeoxycholic acid was used as VOD prophylaxis beginning at a mean of 33 days prior to onset of VOD. As the cellular target of hepatic VOD is as yet unidentified, it is uncertain whether ursodiol or other common characteristics of patients with late onset VOD influence the pathogenesis and natural history of this disease. We believe that the uncommon clinical entity of late onset VOD, a potentially fatal regimen-related toxicity, should not be ignored as a diagnosis of liver disease after 3 or more weeks following HDC and SCT. Keywords: late onset VOD; high-dose chemotherapy; peripheral blood stem cell transplantation; ursodeoxycholic acid; VOD risk factors Hepatic veno-occlusive disease (VOD) is the leading cause of regimen-related morbidity and mortality in the first 2 months following high-dose chemotherapy (HDC) and bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT) 1 with an incidence ranging from 0% to 70%. 2 VOD was originally defined as a clinical syndrome occurring by day +20 following SCT with at least two of the following features: jaundice, tender hepatomegaly and ascites or unexplained weight gain. 3 In the absence of histological confirmation, the combination of all three clinical features has been reported to have a specificity of 92% and sensitivity of 56%. 2,4 It is now clear that VOD can develop in patients beyond day +20, thus necessitating that a time limit be omitted from the diagnostic criteria for VOD. 1,2,5 The entity of late onset VOD is not well described. Beyond the third and fourth weeks post SCT, the main differential diagnoses of liver injury include infective causes, acute GVHD, drug-related insults and recurrent disease. 6 Given that severe VOD is associated with a mortality approaching 100% by day +100 with no truly effective therapeutic options, 1,3,5,7 early detection and institution of appropriate supportive measures are vital. VOD must not be ignored as a diagnostic consideration beyond 3 to 4 weeks post SCT in patients with clinical or biochemical liver dysfunction and/or weight gain. Here, we review the clinical ...

Transjugular intrahepatic portosystemic shunt for the treatment of sinusoidal obstruction syndrome in a liver transplant recipient and review of the literature

“…In agreement with other authors, 16,27,28 we believe that when there is no response to medical treatment, prompt TIPS placement should be contemplated. When multiorgan failure ensues, the window of opportunity may close.…”

“…In patients who have undergone SCT and are receiving cyclophosphamide, SOS occurs within 10 to 20 days, whereas with other regimens, SOS appears later. 16 In LT recipients, the interval before SOS is longer (a mean of 9 weeks after the procedure). 17 Posttransplant ascites is a serious clinical dilemma, and persistent ascites can be indicative of venous outflow obstruction syndrome; therefore, SOS should be excluded.…”

“…Similarly, a body weight increase greater than 20% was associated with a dismal prognosis. 16 Prognostic models for LT patients with SOS have not been validated, and additional studies are needed.…”

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

“…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.…”

Noncirrhotic Portal Hypertension

“…With other regimens, it may occur later. 141 After liver transplantation, VOD occurs over wide intervals, with a mean of 9 weeks after the transplant surgery. 142 Viral infections, graft versus host disease, sepsis, heart failure, and tumoral infiltration of the liver need to be excluded.…”