Tumor Lysis Syndrome OL

8/20/2019 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



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Respiratory findings:

cough, hoarseness,

dyspnea, orthopnea, and chest pain; Central nervous system findings:

headache,

visual impairment,

lethargy,

irritability and anxiety



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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



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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


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


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, &acute 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]

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Tumor Lysis Syndrome OL