Superior vena cava syndrome (SVCS)

Hyperleukocytosis
Tumor lysis syndrome

obstruction/compression of superior vena cava

may coexist with tracheal compression (superior
mediastinal syndrome)

Children: high risk due to thin wall & small

intraluminal diameters of SVC
Susceptible to external compression

many adjacent lymph nodes sandwiching the vena

cava and the adjacent thymus

prominent in pediatric patient.

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Intrinsic causes:
vascular thrombosis, e.g., following catheterization

Extrinsic causes: malignant anterior mediastinal

tumors:
Hodgkin lymphoma

Non-Hodgkin lymphoma
Teratoma or other germ cell tumor
Thyroid cancer
Thymoma

Most commonly caused by:

mediastinal mass
thrombosis: can develop at during therapy

Respiratory findings:
cough, hoarseness,

dyspnea, orthopnea, and chest pain;

Central nervous system findings:

headache,
visual impairment,
lethargy,

irritability and anxiety

Signs include:

swelling,
plethora,
cyanosis of the face, neck, upper extremities;
edema of the conjunctivae;
distended neck and chest wall veins;
diaphoresis;
wheezing & stridor;
pulsus paradoxus

complete blood count & peripheral smear

bone marrow aspirate
biopsy
thoracentesis: therapeutic & diagnostic
biopsy of a superficial node
tumor markers -HCG & alpha-fetoprotein

Supportive care:
Avoid : (to prevent respiratory arrest)
Supine position
Stress
Sedation

Patient may have to be intubated

Diagnosis should be made quickly in the least

invasive manner:
chest radiograph /CT (if tolerated)
blood test: Complete blood count, LDH, uric acid,

-fetoprotein, -hCG
Echocardiogram, if no evidence of mass on
radiograph
Determine anesthesia risk. If high risk, perform
the least invasive technique with local anesthesia

Therapy:
Do not wait tissue diagnosis
empiric treatment as a life-saving measure

Radiotherapy
Steroids

Prednisolone 60 mg/m2/day (2 mg/kg/day) or

methylprednisolone 48 mg/m2/day (1.6 mg/kg/day)

divided into 2 daily doses

Biopsy as soon as possible specific

chemotherapy

Definition:
total leukocyte count >100,000/L

Epidemiology:
913% of children with acute lymphocytic

leukemia (ALL)
522% of children with acute myeloid leukemia
(AML)
More common in chronic myeloid leukemia (CML)

blasts in microcirculation:
sludge tissue oxygenationtissue ischemia
High metabolic rate of blasts and cytokines
production contribute to tissue hypoxia.
Thrombi in pulmonary circulation: vascular
damage pulmonary hemorrhage and edema.
blasts in cerebral circulation: risk of cerebral
hemorrhage and cerebrovascular ischemia.

Complications:
metabolic disturbances (tumor lysis

syndrome/TLS) : in ALL
hyperviscosity-associated symptoms more
frequent in AML
(Myeloblasts are larger, less deformable & more
adherent to vasculature than lymphoblasts)
leukostasis /thrombosis more prevalent in AML

Symptoms :
Cardiopulmonary : dyspnea, hypoxia, and right

ventricular heart failure

CNS : blurred vision, sudden deafness, confusion,
stupor
Genitourinary: oliguria, anuria, priapism.
Vascular : DIC, retinal hemorrhage, myocardial
infarction, renal vein thrombosis.

Aggressive hydration:
Volume 24 x maintenance (2-3L/m2/day or more)

Use 5% Dx saline

Diuresis: maintain urine output >2 mL/m/hour

Furosemide 0.51 mg/kg
Mannitol 0.5 g/kg (if patient has oliguria

unresponsive to hydration and furosemide)

Uric acid reduction

Allopurinol 300 mg/m2/day or 10 mg/kg/day PO

(max dose 800 mg/day)

or 200 mg/m2/day IV (max dose 600 mg/day)

Leukocyte reduction
Leukopheresis or exchange transfusion (for

infants) if the patient is symptomatic

Monitoring:
Signs & symptoms of complication (leukostasis,

TLS)
Check complete blood count/12-24 hour
Blood gas analysis/day or if necessary
Electrolyte: Na, K, Cl, P, Ca, Mg/day
Diuresis and fluid balance/6 hour

Rapid release of intracellular metabolites

(Phosphat, K, uric acid) from necrotic tumor
cells > excretory capacity of kidneys

Laboratory TLS
abnormal serum values

present within 3 days before or 7 days after

instituting chemotherapy

Clinical TLS
laboratory TLS + 1 of the following:
increased serum creatinine (1.5 times normal)
cardiac arrhythmia/sudden death
seizure

Cairo-Bishop definition of laboratory tumor lysis syndrome

Element

Value

Uric acid

8 mg/dL

Change from
baseline
25 % increase

Potassium

6 mEq/L

25 % increase

Phosphorus
Calcium

6.5 mg/dL
7 mg/dL

25 % increase
25 % decrease

Coiffier B, et al. J Clin Oncol 2008; 26:2767

Monitoring
intensive supportive care + cardiac monitoring

urine output and fluid balance

frequent serial measurement of electrolytes (Ca,

P, Na, K, Mg) creatinine, and uric acid

IV hydration
Urinary alkalinization
Hypouricemic agents

Goal:
improve renal perfusion and glomerular filtration,
induce a high urine output to minimize the likelihood of uric

acid or Ca phosphate precipitation in the tubules.

2008 International Expert Panel recommendation:

2-3 L/m2/day (or 200 mL/kg/day in children weighing 10 kg)
Maintain urine output 80 -100 mL/m2/hour (2 mL/kg/hour, or 4-

6 mL/kg/hour if 10 kg).
Diuretics can be used to maintain urine output.
Loop diuretics (furosemide) appear preferable because they not
only induce diuresis, but may also increase potassium secretion.

Hydration fluid:
Initial: 5% Dx saline

Patients with hyponatremia or volume depletion:

isotonic saline

IV hydration
Urinary alkalinization
Hypouricemic agents

Urinary alkalinization:
Target: urine pH 6.5 - 7.0

increase uric acid solubility, diminishing the

likelihood of uric acid precipitation in the tubules

but promoting Ca phosphate deposition if pH >7.5
started when serum uric acid level is high and
discontinued when hyperphosphatemia develops
Use bicnat 20-40 mEq/500 mL hydration fluid
Check urine pH every 6 hour

IV hydration
Urinary alkalinization
Hypouricemic agents

Allopurinol
hypoxanthine analog, inhibits xanthine oxidase, blocks the metabolism
of hypoxanthine and xanthine to uric acid.
decreases the formation of new uric acid
reduces the incidence of obstructive uropathy
Limitations :
Allopurinol does not reduce serum uric acid concentration before
treatment is initiated.
preexisting hyperuricemia (serum uric acid 7.5 mg/dL), rasburicase is
preferred
Risk of xanthinuria, deposition of xanthine crystals in renal tubules, &
acute kidney injury

Dose and administration

50 - 100 mg/m2/ 8 hours (max300 mg/m2/day)
or 10 mg/kg/day in divided doses
IV allopurinol: 200 - 400 mg/m2/day, (max 600 mg/day)

Dose reductions:
reduce by 50 % in acute kidney injury
reduce by 65-75% in patients being treated with

mercaptopurine

Treatment is initiated 24-48 hours before induction

chemotherapy.
Continued for up to 3-7 days afterward

Electrolyte abnormalities
Hyperkalemia
can cause sudden death due to cardiac dysrhythmias.
limit K & P intake during the risk period for TLS.
Measure serum potassium every 4-6 hours,
continuous cardiac monitoring,
Glucose + insulin or beta-agonists, & calcium gluconate
If needed, hemodialysis and hemofiltration effectively
removes potassium.

Electrolyte abnormalities
Symptomatic hypocalcemia
calcium at the lowest doses required to relieve symptoms.
Do not give Ca until hyperphosphatemia is corrected
Except: severe symptoms of hypocalcemia (eg, tetany or
cardiac arrhythmia) should be considered for calcium
replacement regardless of the phosphate level.
Asymptomatic hypocalcemia do not require treatment.
Hyperphosphatemia
aggressive hydration & phosphate binder therapy

Renal replacement therapy (dialysis):

Severe oliguria or anuria

Persistent hyperkalemia
Hyperphosphatemia-induced symptomatic

hypocalcemia

References:
Lanskowsky. Manual of Pediatric Hematology and Oncology, 5 ed.

2011
Chan. Andersons Pediatric Oncology. 2005
Lewis MA et al. Oncologic Emergencies: Pathophysiology,
Presentation, Diagnosis, and Treatment CA Cancer J. Clin 2011;61:287314
Coiffier B, et al. J Clin Oncol 2008; 26:2767

Contact:
Dr. H.A Sjakti, SpA(K)
Email: sjakti@ikafkui.net