Oncology

Sinusoidal obstruction syndrome (SOS)/s "venoocclusive disease" (VOD)

SOS/VOD:

Sinusoidal obstruction syndrome (SOS) originally described as "venoocclusive disease" (VOD) is a serious hepatic injury that can occur following drug administration.²⁴

This syndrome can be a life-threatening complication following hemopoietic stem cell transplant.

Sinusoidal endothelial cells and hepatocytes of the hepatic acinus zone 3 become damaged by toxic metabolites resulting from the conditioning regimen.

Hepatic Lobule Organization²⁶

Yager JD Hepato and Renal Toxicology Johns Hopkins Bloomberg School of Public Health http://ocw.jhsph.edu/courses/publichealthtoxicology/PDFs/Lecture6_Yager.pdf 2008

SOS can occur following even a single infusion of drug and presents in the acute setting within 1-3 weeks of exposure.
Both chronic and subacute forms of SOS have been described and can become apparent in the weeks to years.
Diagnosis of SOS depends on clinical criteria that can include weight gain, ascites, tender hepatomegaly and jaundice.²⁴

In the context of hemopoietic stem cell transplant (HSCT), SOS/VOD is more likely to occur in the first month.²⁵
- There is a wide incidence range associated with SOS (5%-60%).
  - This range depends not only on risk factors, transplant types, conditioning regimens but also on the clinical basis used for diagnosis.
- At this time (2015) SOS is more common following allogenic HSCT a.k.a. allo-HSCT following conditioning with myeloablative protocols.
  - Here, the incidence appears around 10%-15%.²⁵
  - Other estimates suggest that about 3%-10% of patients will develop SOS, depending on the conditioning regimen intensity.²⁷
    - Peak incidence during the first month occurs at day 16.
    - Factors that increase the likelihood of SOS include:
      - Previous treatment with intensive chemotherapy protocols
      - Pretransplant hepatitis, and
      - Drug protocols involving more intense conditioning approaches.²⁷
  - The overall mortality rate of SOS is estimated at 30%. Progressive liver failure results in a "terminal hepatorenal syndrome."²⁷
  - By contrast, reduced intensity conditioning and autologous HSCT (auto-HSCT) is associated with an incidence of <5%.²⁵
Severity of SOS is highly variable. In the mild form the syndrome may resolve within a few weeks.²⁵
- In a severe presentation, which includes multiorgan failure, mortality rates may exceed 80%.

Early morphological change in SOS is noted in sinusoidal endothelial cells resulting in hepatic sinusoids zone 3 obstruction in the hepatic acinus.

Sinusoidal Obstruction Syndrome²⁴

"This biopsy was taken from a 48 year old man who developed signs of sinusoidal obstruction syndrome following bone marrow transplantation. "There is congestion and hemorrhage in zone 3 with spillage of red blood cells in between hepatocytes. "This change is associated with hepatocyte necrosis (arrow). "The central vein is not clearly seen, but the location is indicated (V). "The portal area (P) is also marked for reference."²⁴ Kleiner DE Histologic Image: Sinusoidal Obstruction Syndrome, Laboratory of Pathology National Cancer Institute. ²⁴ o

Sinusoidal Obstruction Syndrome24

"Here a central vein (V) is clearly seen. There is hemorrhage in the vein wall and narrowing of the lumen by loose connective tissue.²⁴ Kleiner DE Histologic Image: Sinusoidal Obstruction Syndrome, Laboratory of Pathology National Cancer Institute. ²⁴

Endothelial pathology following HSCT is not limited to sinusoidal lining and can result in many endothelial syndromes following transplant including “capillary leak syndrome, engraftment syndrome, transplant-associated microangiopathy or diffuse alveolar hemorrhage.”²⁵

Case example: "Mild sinusoidal obstruction syndrome after hematopoietic cell transplantation." (Case study provided by Dr. George B. McDonald from the files of the Fred Hutchinson Cancer Center)²⁴

"A 56-year-old woman with myelofibrosis and agnogenic myeloid metaplasia underwent allogenic hematopoietic cell transplantation after the conditioning regimen of oral busulfan (16 mg/kg with therapeutic drug monitoring), followed by intravenous cyclophosphamide (120 mg/kg) and prophylactic ursodiol therapy.
One week later she became jaundiced and had mild hepatic tenderness.

She gained approximately 10% of her initial body weight.

Liver enzyme levels did not change and serum creatinine was stable (0.7 to 1.0 mg/dL).

She had complications of staphylococcal bacteremia and pulmonary fungal infection and was treated for gastrointestinal graft-vs-host disease, but responded to antibiotic and antifungal therapy and was discharged 28 days after the transplant at which time her weight was back to baseline."²⁴
Laboratory Values for the Case Above²⁴

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