OBJECTIVES
Present a case Hepatic Sinusoidal
Obstruction Syndrome (HSOS) on a post
STEM Cell Transplant patient
Discuss current issues in the diagnosis,
prevention and management of HSOS
GENERAL DATA
JM
32/M
Guam
Single
American
Prosecution Lawyer
CHIEF COMPLAINT
For stem cell transplant
REVIEW OF SYSTEMS
General: no weight loss/gain, no heat/cold intolerance
Eyes: no blurring of vision, color blindness, discharge,
lacrimation, redness
Ears: no deafness, tinnitus, otorrhea, otalgia
Nose: no nasal obstruction, stuffiness, rhinorrhea
Mouth/Throat: no oral sores, tooth ache, sore throat
Respiratory/Cardiovascular: no cough, colds, difficulty of
breathing, phlegm production, chest pain, palpitations
Gastrointestinal: no abdominal pain, BM changes, vomiting,
melena, hematochezia
Skin/Musculoskeletal: no muscle pains, joint pains
Nervous: no change in sleeping pattern, involuntary
movements, seizures, dizziness disturbance of smell, vision,
paresthesias, difficulty chewing, facial weakness, difficulties in
speech and swallowing, paralysis, muscle wasting
FAMILY HISTORY
No thyroid disease, rheumatologic
condition, HPN, DM, blood dyscrasia
PHYSICAL EXAM
General: Conscious, coherent, not in distress, comfortable in bed
Vital signs: BP 122/71 mm Hg, HR 71 RR 18cpm T 37.5, O2 99% at
room air
74.6 kg 176 cm BMI 24.08
Skin: Warm moist skin, no ecchymosis/skin changes, no pallor, no
jaundice
HEENT: Pink palpebral conjunctiva, anicteric sclerae, tonsils not
enlarged, non hyperemic posterior pharyngeal wall, Neck veins are not
engorged, thyroid not enlarged, non tender, no bruits, no CLADS
Chest: Symmetrical chest expansion
Heart: Adynamic precordium, regular rhythm; no heaves, lifts or thrills;
apex beat at the 5th intercostal space, MCL; no murmurs, distinct S1 and
S2
Abdomen: Abdomen flat, normoactive bowel sounds, soft, no
direct and indirect tenderness, no mass, no hepatosplenomegaly, no
CVA tenderness
Extremities: Pulses full and equal, no ROM limitations, no pedal edema
SALIENT FEATURES
SUBJECTIVE
Dx case of preB ALL s/p
Hyper CVAD
No intake of supplements
or other drugs
No skin lesion
Non smoker, denies illicit
drug use
No rheumatologic disease,
no thyroid disease, no
blood dyscrasia, no DM, no
HPN
OBJECTIVE
32 yo Male
BP 122/71 HR 71 RR 18 T 36.8
74.6 kg 176 cm BMI 24.08
Abdomen soft non tender
No hepatosplenomegaly
No pedal edema
WORKING DIAGNOSIS
Pre B ALL in remission
Baseline Laboratories
CBC: 10.3/ 32.4/ 3.42/ 3640/ 68-20-1-9-2/
164000/95-30-32
Blood Chemistry: Crea 0.63 UA 6.1 BUN
9 K 4 Mg 1.6 TB 0.49 CB 0.10 UB 0.39
ALP 89 TP 6.3 Alb 3.6 Glob 2.7
CXR: Interval regression of RLL linear
densities
12LECG: NSR, NSSTTWC
WA CT Scan: Liver not enlarged;
Complications
Graft Rejection
Hospital Acquired Infections
Elevated Bilirubin
Hemorrhagic Cystitis
Graft Rejection
D0 received stem cells from his father.
No untoward incident noted.
Serial CBC monitoring started due to
decreasing counts (RBC, WBC, PC)
Given routine irradiated PRBS and platelet
transfusion
Started on GCSF
Graft Rejection
D+13 still pancytopenic
HLA antibody to class I and II NEGATIVE
GCSF increased from 300 to 600 mcg daily
Tacrolimus was increased to 3 tabs BID
still neutropenic and noted to be septic
Graft Rejection
D+19 pegfilgrastim 6mg SQ every 5
days
D+41 remains pancytopenic and
requires PRBC and platelet transfusion
developed pseudomonas infection
Platelets do not seem to be responding
adequately
Assessment:
Pre B ALL s/p 5 cycle chemo
s/p BMA Failed Engraftment;
s/p Haploid HSCT (6/11)
On interim
D+70
O2 sats noted to be ranging from 86% to 92%
Still febrile at 39-40C
Started on O2 via NC with increase in O2 demand warranting
use of BIPAP
Assessment:
1. Sepsis secondary to
a. Bacteremia (Pseudomonas
aeruginosa 8/20, 8/16, 8/14, 8/10, 8/2;
Enterococcus faecium 8/12;
Enterococcus faecium BNLAR 8/10;
Pseudomonas and Stenotrophomonas
maltophilia)
b. HAP
2. Impending Respiratory Failure sec to
HAP
Elevated Bilirubin
Noted progressive increase in weight D-1 74.6kg -> D+18 83kg
D+10 - abdominal pain progressive until referred to pain service D+18
D+58
Bilirubin 1st noted to be elevated (0.49 to 4.91)
WA UTZ showed hepatosplenomegaly, mild fatty liver changes
D+60
further increase in bilirubin (4.91 to 6.3)
Referred to GI service; A> Drug induced hepatitis
Reffered to hepatologist ; A> Hepatic sinusoidal obstruction syndrome
D+73
hepatosplenomegaly, with interval increase in size
26.5 cm (24.0)
Assessment:
Obstructive jaundice secondary to
Hepatic Sinuisoidal obstruction
syndrome sec to HSCT vs cholestasis
secondary to sepsis
HSOS Pathogenesis
typically occurs in hematopoietic cell transplantation
begin with injury to the hepatic venous endothelium
preexisting liver disease increases the risk of developing
SOS
chronic hepatitis more susceptible to the cytoreductive regimen
abnormally express adhesion molecules and procoagulant factors
HSOS Pathogenesis
High power view of a reticulin stain of a
liver biopsy from a patient with sinusoidal
obstruction syndrome. There is prominent
perivenular fibrosis
Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients.
McDonald GB, Hinds MS, Fisher LD, Schoch HG, Wolford JL, Banaji M, Hardin BJ, Shulman HM, Clift RAAnn Intern Med.
HSOS Prevention
Minimizing exposure to hepatotoxic agents
avoid medications, supplements, and other substances that are commonly
associated with liver injury
Iron chelation for patients with liver dysfunction due to iron overload
Consider the preparative regimen
Pt. cirrhosis who receive myeloablative conditioning
Reduced intensity conditioning protocols like in those using busulfan
HSOS Prophylaxis
variability in the use of pharmacologic prophylaxis for SOS among
transplant centers
Allogeneic HCT
- UDCA (12 mg/kg daily, divided in two doses) is started from the
day preceding the preparative regimen and continued for
the first
three months of transplantation
Autologous HCT
- Heparin (100 units/kg per day by continuous intravenous infusion)
is started on the first day of the preparative regimen and
continued until hematopoietic engraftment
BCSH/BSBMT guideline: diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following
haematopoietic stem cell transplantation. Dignan FL, Wynn RF, Hadzic N, Karani J, Quaglia A, Pagliuca A, Veys P, Potter MN. Br J
HSOS Treatment
Supportive care is a key factor in the management of all
patients with SOS.
Daily weights and measures of fluid intake and output are critical to
maintaining euvolemia
Minimizing exposure to hepatotoxic agents
Pain Control
Paracentesis - for ascites that is associated with discomfort or
pulmonary compromise
HSOS Treatment
Supportive care is a key factor in the management of all
patients with SOS.
Daily weights and measures of fluid intake and output are critical to
maintaining euvolemia
Minimizing exposure to hepatotoxic agents
Pain Control
Paracentesis - for ascites that is associated with discomfort or
pulmonary compromise
HSOS Treatment
Defibrotide
treatment of adults and children with SOS with renal or
pulmonary dysfunction following hematopoietic cell
transplantation
20 to 30 percent of patients are expected to be alive beyond day
+100
6.25mg/kgis administered intravenously every six hours and
continued for a minimum of 21 days may be extended for a
maximum of 60 days
most common toxicities are hypotension, diarrhea, nausea,
vomiting, and epistaxis
no phase III randomized trials evaluating the use ofdefibrotidefor
the treatment of patients with SOS
HSOS Treatment
Liver transplantation
successfully performed in small numbers of patients with SOS
majority of patients not capable of undergoing such a rigorous surgical
procedure
patients at risk for recurrent malignancy are low-priority candidates for liver
transplant
BCSH/BSBMT guideline: diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following
haematopoietic stem cell transplantation. Dignan FL, Wynn RF, Hadzic N, Karani J, Quaglia A, Pagliuca A, Veys P, Potter MN. Br J
Summary
HSOS is a formidable challenge both for patients
undergoing HSCT and for their physicians.
HSOS contributes considerably to transplantationrelated morbidity and mortality.
A high clinical index of suspicion is needed to
correctly and consistently identify patients with
HSOS
Prophylactic interventions are very critical
Therapeutic agents such as defibrotide still under
trial