Pediatric Oncology Flashcards
To prepare for College Exam
What is Tumor lysis syndrome (TLS)?
Deftn: Acute, life-threatening disease among children that is associated with the initiation of cytoreductive therapy in the treatment of malignancy.
Characteristic findings:
Raised: hyperuric acid, phosphate, K+, urea
Low: Ca+hypocalcemia, and uremia
Cplxns: cardiac arrhythmia, seizures, renal failure,
and sudden death.
What is the Diagnostic Criteria for TLS
(Cairo Bishop grading for Lab & Clinical TLS)
What is the Cairo-Bishop Grading of Clinical Tumor Lysis Syndrome (TLS)?
How do Allopurinol and Rasburicase work?
What are the CLINICAL FEATURES of TLS?
Timing:
- Within 12 to 72 > initiation of cytotoxic therapy
- Can occur < therapy (spontaneous) or extend > 72 hrs
Symptoms include:
nausea, vomiting, diarrhea, anorexia, weakness, lethargy,
hematuria, muscle cramps, tetany, and syncope.
Cplxns:
Cardiac dysrhythmias, seizures, sudden death
Pathogenesis- Hyperuricemia
Hyperuricemia with hyperphosphatemia, can lead to acute kidney injury.
Mecanism:
-Purine containing nucleic acids released
into the serum are catabolized to uric acid and, when
present in excess, surpass the renal tubular capacity for uric
acid excretion.
-Uric acid is poorly soluble in water, and the solubility is markedly reduced in the physiologically acidic environment of the distal tubules and collecting system. Thus, uric acid crystals readily precipitate when concentrated in the renal circulation, leading to renal tubule obstruction and obstructive uropathy, with compromised glomerular filtration and reduced
urine output.
How does Allopurinol work?
Allopurinol blocks uric acid synthesis leading
to accumulation of the uric acid precursors xanthine and
hypoxanthine, of which hypoxanthine is more soluble and
more easily excreted than uric acid.
How does Rasburicase work?
-Urate oxidase oxidizes uric acid to the water-soluble and
readily excreted metabolite allantoin.
- Rasburicase (urate oxidase) reduces uric acid levels without
increasing the levels of uric acid precursors, and therefore
does not risk xanthine nephropathy.
What is the role of Hyperphosphatemia and Hypocalcemia in TLS?
- Tumor cells have higher (PO4) than their normal cells
- In TLS renal tubular excretion of (PO4) becomes saturated. - excess serum phosphate
- Excess (PO4) binds to Ca+– low (Ca) + Ca PO4 deposition - - Low (Ca) Sx:
- Arrythmias, seizures, Nephrocalcinosis -renal tubulular nephrolithiasis and cause or further provoke an obstructive
uropathy.
Role of high K+ in TLS?
K+ is an ICF electrolyte regulated through renal excretion.
TLS HR K+ …cardiac dysrhythmias and sudden death.
Ca+ stabilizes the cardiac membrane, Low Ca+ exacerbates HR Ca+- induced cardiotoxicity and cardiac dysrhythmias.
HR Ca+ > 7.0 mEq/L(hyperkalemic emergency) and can be potentiated by ongoing TLS, Low Ca+, and/or renal failure
Role of Acute Renal Injury in TLS?
AKI - independent predictor of short + long-term TLS mortality
Mecnms:
Crystal-dependent and crystal-independent mechanisms.
-
Crystal-dependent mechanisms
- obstructive uropathy.
- Decreased urinary outputcan result in volume overload and cardiac failure, which can exacerbate crystal precipitation.
Urine alkalinization to > pH 6.5 not in use now
2. Crystal-independent mechanisms
-loss of autoregulation, renal vasoconstriction,
and local inflammation
-Tumor lysis–induced hypercytokinemia can result in hypotension, systemic inflammation, and multiorgan failure
What are the Risk factors in TLS?
Monitoring blood tests?
- Get baseline analyte values prior to Rx:
uric acid, electrolytes, LDH, and creatinine,
HIGH RISK: every 4 to 6 hours
INTERMEDIATE RISK: every 6-8 hours
LOW RISK: every 24 hours
N.B.
- uric acid levels may remain normal in patients with an emerging TLS ON ALLOPURINOL
- For rasburicase, laboratories must develop
protocols to collect uric acid samples in prechilled tubes that
are placed immediately on ice and kept on ice throughout
rapid transport to the laboratory for immediate run on the
instrument to prevent rapid in vitro uric acid breakdown,
and a spuriously low assay result.
Role of hydration in TLS?
- Maintaining a high urine output with adequate hydration
- most important aspect of TLS prevention and
management, because this improves renal perfusion and
glomerular filtration, and minimizes acidosis, all of which
serve to prevent the precipitation of uric acid and calcium
phosphate crystals in the renal tubules.
- intermediate-to-high risk & for established TLS: hyperhydration with NS to maintain equal
fluid balance and a high urine output.
- K+, PO4, and Ca+ should NOT be added to the hydration solution.
- Monitored Volume status to prevent volume overload, particularly in patients with renal failure or cardiac dysfunction, and diuretics may be necessary to maintain urine output.
What is the role of Allopurinol in TLS?
“Preferred prophylactic in low-to-intermediate risk patients”
- *Limitations:**
1. As it it does not break down preexisting uric acid, urate nephropathy can develop in the 3 days it takes to have a therapeutic effect. SO is NOT the preferred agent in the presence of hyperuricemia.
Furthermore, xanthine nephropathy must be considered in patients who develop TLS while receiving appropriate prophylactic therapy with allopurinol.
- allopurinol is excreted by the kidneys and must be dose reduced or discontinued in patients with renal insufficiency.
- hypersensitivity reactions have occurred. Asian populations have a higher frequency of the HLAallele, which is associated
with severe adverse cutaneous reactions with allopurinol
use.
- because allopurinol reduces purine degradation,
chemotherapeutic agents, such as 6-mercaptopurine
and azathioprine, must be dose reduced by 50% to 70%
when concurrently administered.
N.B. Any patient who develops TLS while receiving allopurinol prophylaxis should be switched to rasburicase
