Tumor Lysis Syndrome OL
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Transcript of Tumor Lysis Syndrome OL
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Superior vena cava syndrome (SVCS)
Hyperleukocytosis
Tumor lysis syndrome
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obstruction/compression of superior vena cava may coexist with tracheal compression (superior
mediastinal syndrome)
Children: high risk due to thin wall & smallintraluminal diameters of SVC
Susceptible to external compression many adjacent lymph nodes sandwiching the vena
cava and the adjacent thymus
prominent in pediatric patient.
http://www.webmd.com/pain-management/guide/whats-causing-my-chest-pain
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Escolarship.org Nejm.com
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Intrinsic causes:
vascular thrombosis, e.g., following catheterization
Extrinsic causes: malignant anterior mediastinaltumors:
Hodgkin lymphoma
Non-Hodgkin lymphoma
Teratoma or other germ cell tumor
Thyroid cancer
Thymoma
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Most commonly caused by:
mediastinal mass
thrombosis: can develop at during therapy
http://www.webmd.com/pain-management/guide/whats-causing-my-chest-pain
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Respiratory findings:
cough, hoarseness,
dyspnea, orthopnea, and chest pain; Central nervous system findings:
headache,
visual impairment,
lethargy,
irritability and anxiety
http://www.webmd.com/pain-management/guide/whats-causing-my-chest-pain
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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
http://www.webmd.com/pain-management/guide/whats-causing-my-chest-pain
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complete blood count & peripheral smear
bone marrow aspirate
biopsy thoracentesis: therapeutic & diagnostic
biopsy of a superficial node
tumor markers ß-HCG & alpha-fetoprotein
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Supportive care:
Avoid : (to prevent respiratory arrest)
▪
Supine position▪ Stress
▪ Sedation
Patient may have to be intubated
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Diagnosis should be made quickly in the least
invasive manner:
chest radiograph /CT (if tolerated) blood test: Complete blood count, LDH, uric acid,
α-fetoprotein, β-hCG
Echocardiogram, if no evidence of mass onradiograph
Determine anesthesia risk. If high risk, performthe least invasive technique with local anesthesia
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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 specificchemotherapy
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Definition:
total leukocyte count >100,000/µL
Epidemiology: 9–13% of children with acute lymphocytic
leukemia (ALL)
5–22% of children with acute myeloid leukemia(AML)
More common in chronic myeloid leukemia (CML)
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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 cerebralhemorrhage and cerebrovascular ischemia.
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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
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Symptoms :
Cardiopulmonary : dyspnea, hypoxia, and right
ventricular heart failure CNS : blurred vision, sudden deafness, confusion,
stupor
Genitourinary: oliguria, anuria, priapism.
Vascular : DIC, retinal hemorrhage, myocardialinfarction, renal vein thrombosis.
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Aggressive hydration:
Volume 2–4 x maintenance (2-3L/m2/day or more)
Use 5% Dx ¼ saline Diuresis: maintain urine output >2 mL/m/hour
Furosemide 0.5–1 mg/kg
Mannitol 0.5 g/kg (if patient has oliguriaunresponsive to hydration and furosemide)
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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 (forinfants) if the patient is symptomatic
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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
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Rapid release of intracellular metabolites
(Phosphat, K, uric acid) from necrotic tumor
cells > excretory capacity of kidneys
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Laboratory TLS
≥ abnormal serum values
present within 3 days before or 7 days afterinstituting chemotherapy
Clinical TLS
laboratory TLS + ≥ 1 of the following:
▪ increased serum creatinine (≥1.5 times normal)
▪ cardiac arrhythmia/sudden death
▪ seizure
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Element Value Change frombaseline
Uric acid ≥8 mg/dL 25 % increase
Potassium ≥6 mEq/L 25 % increase
Phosphorus ≥6.5 mg/dL 25 % increase
Calcium ≤7 mg/dL 25 % decrease
Cairo-Bishop definition of laboratory tumor lysis syndrome
Coiffier B, et al. J Clin Oncol 2008; 26:2767
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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
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IV hydration
Urinary alkalinization
Hypouricemic agents
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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.
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Hydration fluid:
Initial: 5% Dx ¼ saline
Patients with hyponatremia or volume depletion:isotonic saline
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IV hydration
Urinary alkalinization
Hypouricemic agents
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Urinary alkalinization:
Target: urine pH 6.5 - 7.0
increase uric acid solubility, diminishing thelikelihood of uric acid precipitation in the tubules
but promoting Ca phosphate deposition if pH >7.5
started when serum uric acid level is high anddiscontinued when hyperphosphatemia develops
Use bicnat 20-40 mEq/500 mL hydration fluid
Check urine pH every 6 hour
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IV hydration
Urinary alkalinization
Hypouricemic agents
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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 ispreferred
Risk of xanthinuria, deposition of xanthine crystals in renal tubules, ´ kidney injury
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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 inductionchemotherapy.
Continued for up to 3-7 days afterward
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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 effectivelyremoves potassium.
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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 calciumreplacement regardless of the phosphate level.
Asymptomatic hypocalcemia do not require treatment. Hyperphosphatemia
aggressive hydration & phosphate binder therapy
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Renal replacement therapy (dialysis):
Severe oliguria or anuria
Persistent hyperkalemia Hyperphosphatemia-induced symptomatic
hypocalcemia
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References: Lanskowsky. Manual of Pediatric Hematology and Oncology, 5 ed.
2011
Chan. Anderson’s Pediatric Oncology. 2005 Lewis MA et al. Oncologic Emergencies: Pathophysiology,
Presentation, Diagnosis, and Treatment CA Cancer J. Clin 2011;61:287-
314
Coiffier B, et al. J Clin Oncol 2008; 26:2767
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Contact:
Dr. H.A Sjakti, SpA(K)
Email: [email protected]