Biopsy Proven Late-Onset Sinusoidal Obstruction Syndrome Successfully Treated With Defibrotide

Case Report

Ann Hematol Oncol. 2015;2(4): 1031.

Biopsy Proven Late-Onset Sinusoidal Obstruction Syndrome Successfully Treated With Defibrotide

Jamali H1, Ferreira J2, Ahmad I1, Cohen S1, Lachance S1, Kiss T1 and Roy J1*

1Blood and Marrow Transplant Program, Division of Hematology and Oncology

2Division of Pathology; Hôpital Maisonneuve-Rosemont and Université de Montréal, Montréal, Québec, Canada

*Corresponding author: Jean Roy, Division of Hematology-Oncology, Hôpital Maisonneuve-Rosemont, 5415 de l’Assomption, Montréal, Québec, Canada H1T 2M4

Received: February 26, 2015; Accepted: March 10, 2015; Published: March 12, 2015


We report an unusual case of a patient who developed a biopsyproven Sinusoidal Obstruction Syndrome (SOS) more than 4 months after a nonmyeloablative allogeneic sibling transplant. The patient responded to defibrotide treatment with clear improvement in liver function and normalization of radiologic findings. Although a few cases of late-onset SOS have been reported in the literature, we describe, to the best of our knowledge, the first case of late-onset SOS successfully treated with defibrotide after allogeneic hematopoietic stem cell transplantation.

Keywords: Sinusoidal Obstruction Syndrome; Veno-Occlusive Disease; Allogeneic Transplant; Late Complications


Despite decreasing incidence, sinusoidal obstruction syndrome (SOS; formerly veno-occlusive disease, VOD) remains one of the most serious complications after Hematopoietic Stem Cell Transplantation (HSCT) [1-4]. Characterized by a triad of painful hepatomegaly, hyperbilirubinemia and otherwise unexplained fluid retention, SOS typically occurs within 21 days of transplant. However, SOS has been observed later and should be included in the differential diagnosis of liver abnormalities beyond 3 weeks of transplant [5,6]. We describe the outcome of an allogeneic transplant recipient presenting with clinical signs of SOS more than 4 months after transplant; diagnosis was proven by biopsy and liver function recovered with defibrotide treatment.

Case Presentation

The patient was a 67 year old male initially diagnosed with stage IV follicular lymphoma. He was first treated with six cycles of chlorambucil and prednisone with partial response. Disease progression occurred approximately 2 years later; he then received 6 cycles of rituximab, cyclophosphamide, vincristine and prednisone (R-CVP). Two months after the last cycle, disease progressed clinically and radiologically; an inguinal lymph node biopsy revealed transformation into diffuse large B-cell lymphoma. The patient then received 2 cycles of salvage chemotherapy including rituximab, etoposide, methylprednisolone, arabinoside-C, prednisone (R-ESHAP regimen), followed by a nonmyeloablative allogeneic stem cell transplant from a matched sibling donor. Cytomegalovirus (CMV) status of both donor and recipient were positive and there was no ABO mismatch. All CT scans were normal prior to transplant.

Conditioning regimen consisted of ibritumomab tiuxetan (Zevalin®), fludarabine and cyclophosphamide as part of an experimental protocol. The patient received a peripheral blood stem cell graft containing 5.3 x 106 CD34+ cells/kg. Graft-Versus-Host Disease (GVHD) prophylaxis included tacrolimus and mycophenolate mofetil. Platelet and neutrophil engraftment occurred promptly. On day +30, the patient developed mild hepatic cytolysis, with Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) values less than twice the upper limit of normal with normal bilirubin. CMV reactivation was identified by polymerase chain reaction assay and rapidly controlled with valganciclovir.

On day +90 after allogeneic HSCT, the patient was hospitalized for respiratory infection. Shortly after admission, he developed abdominal discomfort with an erythematous skin rash involving 60% of his body surface. Upper gastro-intestinal endoscopy revealed a bulboduodenitis macroscopically compatible with upper gastrointestinal GVHD but biopsy was not performed due to refractory thrombocytopenia (15 x 109/L). Initiation of oral prednisone 1 mg/kg led to rapid skin improvement and hospital discharge.

On day +114, the patient was readmitted for abdominal pain without diarrhea and rapid worsening of liver function tests. There were no signs of GVHD clinically and abdominal exam was unremarkable. ALT and AST increased up to 725 and 808 U/L (both normal <40 U/L) respectively, with a bilirubin up to 257 μmol/L (normal <21 μmol/L). At that time, an abdominal ultrasound showed a normal size homogeneous liver, a patent portal vein with normal blood flow, no biliary tract dilatation and absence of ascites. The abdominal CT scan was also unremarkable. Bone marrow biopsy showed a cellularity of 50% with no lymphoma infiltration. Because of high clinical suspicion of acute GVHD, the patient was treated with ursodeoxycholic acid, intravenous steroids and mycophenolate mofetil. Tacrolimus was discontinued due to probable microangiopathic anemia with secondary thrombocytopenia. The patient’s clinical condition improved and bilirubin level decreased to 80 μmol/L. A repeat abdominal CT scan revealed distal small bowel thickening with trace amount of ascites.

Two weeks later, on day +133, the patient complained of progressive abdominal discomfort and swelling; weight increased from 75 to 80 kg (a 7% increase). Physical examination revealed new onset of enlarged abdominal girth without right upper quadrant tenderness and lower limb peripheral edema. An abdominal Magnetic Resonance Imaging (MRI) showed both homogeneously enlarged liver (18 cm) and spleen (13 cm) with moderate ascites. There were no radiologic signs of nodular regenerative hyperplasia. A liver Doppler ultrasound showed a large amount of ascites, hepatomegaly and patent portal and hepatic veins with signs of revascularization of the para-umbilical vein suggesting portal hypertension. There were no signs of right cardiac failure or pulmonary hypertension on echocardiogram.

On day +161, the patient’s clinical condition was stable on furosemide, prednisone and mycophenolate mofetil with a weight of 68 kg. However, liver function tests worsened, with elevated levels of AST (66 U/L), ALT (105 U/L) and bilirubin (144 μmol/L; conjugated 120) but without renal dysfunction. A trans-jugular liver biopsy was performed and pathologic examination revealed a mild portal lymphocytic infiltrate with bile duct damage along with lobular subacute cholestasis suggestive of toxic drug reaction or, less likely, GVHD. Terminal hepatic veins were the site of mild fibrous intimal obliteration and associated sinusoidal and liver cell plate congestion consistent with SOS (Figure 1,2). Finally, the hepatic parenchyma showed regenerative nodules without fibrosis compatible with Nodular Regenerative Hyperplasia (NRH).

Citation: Jamali H, Ferreira J, Ahmad I, Cohen S, Lachance S, Kiss T and Roy J. Biopsy Proven Late-Onset Sinusoidal Obstruction Syndrome Successfully Treated With Defibrotide. Ann Hematol Oncol. 2015;2(4): 1031. ISSN:2375-7965