Download Complications of Hematopoietic Stem Cell Transplant

Hepatic Veno-occlusive
disease/Sinusoidal obstruction
syndrome
Kristin Wessel, MD
Pre-test
1.
2.
3.
Which of the following chemotherapeutic agents used for conditioning is associated with increased risk for
VOD?
a)
Fludarabine
b)
Cyclophosphamide
c)
Busulfan
d)
Cisplatin
Which of the following is NOT evaluated as part of the criteria for VOD?
a)
Weight
b)
Hepatomegaly
c)
Bilirubin
d)
ALT/AST
What is the mortality rate of VOD?
a)
10%
b)
20%
c)
30%
d)
50%
e)
70%
Pre-test
4. What initial imaging study should you order when you suspect VOD?
a)
Abdominal XR
b)
CT
c)
Ultrasound
d)
MRI
5. A patient in which of the following periods surrounding transplant is at greatest risk for developing VOD?
a)
Conditioning through day +30
b)
Day +30 to day +50
c)
Day +50 to day +100
d)
After day +100
VOD/SOS: Epidemiology
 Potentially life-threatening complication of HSCT
 Incidence in pediatrics 11-31%
 3rd leading cause of death in pediatric HSCT patients
during post-transplant period
 Mortality rate up to 50%
 Usually develops by 30 days post-transplant, but can
occur later
VOD/SOS: Pathogenesis
 Damage to sinusoidal endothelial cells and
hepatocytes secondary to toxicity from conditioning
regimen and alloreactivity in the case of allogeneic
HSCT
 Damage to sinusoidal endothelial cells
 Inciting event cytokine release  collagen production 
cellular debris accumulates in Space of Disse  venular
narrowing and obstruction
 Pro-thrombotic state also contributes to obstruction
 Damage to hepatocytes in zone 3 (centrilobular zone)
 Conditioning regimen toxic metabolites  glutathione
depletion  hepatocyte necrosis
VOD/SOS: Risk factors

Allogenic HSCT > Autologous HSCT

Myeloablative conditioning regimen (MAC)

Conditioning regimen including busulfan, especially in combination with
cyclophosphamide

Immunosuppression, especially with cyclosporine

Pre-existing liver disease

Second HSCT

High-dose TBI

Poor performance status (Karnofsky score <90)

Pediatric-specific risk factors: Primary HLH, adrenoleucodystrophy, osteopetrosis,
thalassemia major, auto-HSCT in neuroblastoma, younger age (<1-2 years)
VOD/SOS: Diagnosis
Modified Seattle Criteria
 At least 2 of the following,
occurring within 20 days of
transplantation:
 Serum bilirubin >34 umol/L
(>2 mg/dl)
 Hepatomegaly with right
upper quadrant pain
 >2% weight gain from
baseline due to fluid
retention
Baltimore Criteria
 Serum bilirubin >34 umol/L
(>2 mg/dl) within 21 days of
transplantation AND at least
2 of the following:
 Hepatomegaly
 >5% weight gain from
baseline
 Ascites
VOD/SOS: Diagnosis
 As treatment for VOD/SOS is mainly supportive, early
detection is critical
 Patients require strict monitoring from start of
conditioning to at least day +40 including daily weights
(at least) and strict I/O
 Pay attention to non-specific complaints of abdominal
pain and discomfort
VOD/SOS: Diagnosis
 Determine severity: Seattle criteria
 Mild: No adverse effects of liver disease, AND no
medications required for diuresis or hepatic pain, AND all
symptoms, signs and laboratory features reversible
 Moderate: Adverse effects of liver disease present, AND
sodium restriction/diuretics required, OR medication for
hepatic pain required, AND all signs, symptoms and
laboratory features reversible
 Severe: Adverse effects of liver disease present, AND
symptoms, signs and laboratory features not resolved by
day +100, OR death
VOD/SOS: Treatment
 Prevention
 Reversal/reduction of risk factors when possible
 Ursodiol or low-dose heparin
 Defibrotide: reduced incidence of VOD/SOS shown in
prospective phase III RCT
 Supportive care: fluid restriction, cautious use of
diuretics
Recap: What residents need to
do on the floor
 Knowing where your patient is in relation to transplant is
important is key. If they are anywhere between conditioning
through day +40, this is a high risk window
 Order daily weights and strict I/O
 Bilirubin must be monitored daily
 If a patient meets the criteria for VOD, let your fellow or
attending know immediately. Keep in mind the mortality rate
is 50%
 Order liver U/S when suspecting VOD. Ascites may be
present. Reversal of flow is a late sign.
References
 Mohty, M et al. Sinusoidal obstruction syndrome/veno-occlusive
disease: current situation and perspectives—a position statement
from the European Society for Blood and Marrow Transplantation
(EBMT). Bone Marrow Transplantation (2015), 1-9.
 Barker, CC et al. Incidence, survival and risk factors for the
development of veno-occlusive disease in pediatric hematopoietic
stem cell transplant recipients. Bone Marrow Transplantation (2003),
32, 79-81.
 Lee et al. Hepatic veno-occlusive disease after hematopoietic stem
cell transplantation: incidence, risk factors and outcome. Bone
Marrow Transplantation (2010), 45, 1287-1293.
 Cefalo et al. Hepatic veno-occlusive disease: a chemotherapy-related
toxicity in children with malignancies. Pediatric Drugs (2010)