2. TUMOR LYSIS SYNDROME
Tumor lysis syndrome (TLS) describes the clinical
and laboratory sequelae that result from the rapid
release of intracellular contents of dying tumor
cells.
It is the single most common oncologic
emergency and a frequent source of inpatient
consultation for nephrologists.
Usually occurs in patients with bulky, rapidly
proliferating, and treatment-responsive tumors
3. Pathophysiology
The rapid release of intracellular ions and
metabolic products into systemic circulation
causes
Hyperuricemia
Hyperkalemia
Hyperphosphatemia
Hypocalcemia
4.
5. Hyperuricemia :results from rapid release and
catabolism of intracellular nucleic acids.
Hyperphosphatemia :results from the rapid
release of intracellular phosphates from
malignant cells.
Hypocalcemia :Hyperphosphatemia can lead to
the development of acute renal failure after
precipitation with calcium to form calcium
phosphate crystals in renal tubules during tumor
lysis syndrome.
Hyperkalemia :results from the kidneys’ inability
to clear the massive load of intracellular
potassium released by lysed tumor.
8. ECG of Hypocalcemia: Prolonged ST segment
and prolonged QTc interval (QTc 537 ms).
9.
10. Cairo-Bishop definition
In 2004, Cairo and Bishop defined a classification
system for tumor lysis syndrome.
Laboratory tumor lysis syndrome: abnormality in two
or more of the following, occurring within three days
before or seven days after chemotherapy.
uric acid > 8 mg/dL or 25% increase
potassium > 6 meq/L or 25% increase
phosphate > 4.5 mg/dL or 25% increase
calcium < 7 mg/dL or 25% decrease
Clinical tumor lysis syndrome: laboratory tumor lysis
syndrome plus one or more of the following:
increased serum creatinine (1.5 times upper limit of
normal)
cardiac arrhythmia or sudden death
seizure
11. Risk Factors
Cancer-Related Risk factors
Large burden of tumour
Neoplastic infiltration of the bone marrow, liver, spleen,
kidneys
Tumour with high mitotic rate
Tumour highly chemosensitive
Haematologic malignancy
Patient-Related Risk Factors
Pre-existing nephropathy
Hyperuricemia
Hypotension
Dehydration
Nephrotoxins (drugs, contrast)
Exogenous potassium or phosphorus intakes
12. Incidence of tumor lysis syndrome in
various malignancies
Burkitt lymphoma
High
diffuse large-B cell lymphoma
Intermediate
ALL WBC count, with .100,000 cells/mm3
highest risk
AML: WBC count .75,000 cells/mm3
High
AML: WBC count 25,000–75,000 cells/mm
Intermediate
AML: WBC count ,25,000 cells/mm
Low
13. Prevention
Identication of patients at risk for the development of
tumor lysis syndrome is the most important in
management so that prophylactic measures may be
implemented before the initiation of therapy
TLS risk stratification model
1- Assessment for evidence of laboratory or clinical
TLS at diagnosis
2- Risk assessment based on malignant disease
type
3- Adjustment of TLS risk based on renal function
14. Prevention
Low risk Adequate hydration
Urine output goals listed
Monitor for signs and symptoms of TLS
Low threshold for intravenous fluids
Consider allopurinol on individual basis
Intermediate
risk
Aggressive hydration + allopurinol prophylaxis (or
febuxostat) up to 7 days
Urine output goals listed
Monitor for signs and symptoms of TLS (starting 8 h after
treatment initiation, laboratory tests every 8–12 h)
High risk Aggressive hydration + rasburicase prophylaxis
Urine output goals listed
Monitor for signs and symptoms of TLS (starting 4–6 h after
treatment initiation, laboratory tests every 6–8 h)
Consider “preventive” admission to intensive care unit,
especially in case of pre-existing cardiac or renal
dysfunction
15. Hydration : Patients with intermediate to high risk should
receive 2–3 L/m2 intravenous (i.v.) crystalloids
Urine output should be maintained within the range of 80–
100 ml/m2/h
Alkalinisation of urine not recommended in the prevention
or treatment of TLS calcium phosphate precipitation the
solubility of xanthine and hypoxanthine significantly
decreases at these pH values.
Xanthine Oxidase Inhibitors : Allopurinol ,Feboxistat
Treatment is generally initiated 24–48 hours before the
start of chemotherapy, if possible.
It is continued for up to 3–7 days after the last day of
chemotherapy
The advised dose of allopurinol in adults is 200–400
mg/m2 daily divided in 1–3 oral doses, with a maximum
16. Feboxstat vs allopurinol
Conclusion: In the largest adult trial carried out in TLS
prevention, febuxostat achieved a significant superior sUA
control with one fixed dose in comparison to allopurinol with
comparable renal function preservation and safety profile.
17. Rasburicase
Rasburicase is a recombinant urate oxidase that is
responsible for the enzymatic conversion of uric acid
to allantoin, which is 5–10 times more soluble than
uric acid.
The initially advised dose in preventive settings was
0.15–0.20 mg/kg i.v. once daily during five days
Single fixed dose of 3 mg rasburicase was shown to
be effective to prevent TLS in the majority of high-risk
adults (Coutsouvelis et al, 2013)
In comparison with generically available allopurinol,
rasburicase is significantly more expensive (up to
$3,600 per 7.5-mg vial)
18. Rasburicase
The antitumour treatment has to start 4–24 hours
after the first administration of rasburicase
No dose adjustments are necessary for renal or
hepatic dysfunction.
The main toxicities are hypersensitivity syndrome,
headache and gastrointestinal complaints.
Fatal haemolysis result when patients with glucose-
6-phosphate dehydrogenase (G6PD) deficiency are
treated with rasburicase .
The use of allopurinol is contraindicated when
rasburicase is used in the treatment or prevention of
TLS, as it can reduce the effectiveness of this
treatment.
19.
20. Treatment
A high level of suspicion, rapid recognition and
prompt treatment are critical in the effective
treatment of this dangerous oncological emergency.
Antitumour therapy should be delayed if possible in
patients at high risk for the development of TLS,
until prophylactic measures are initiated.
Once laboratory or clinical TLS is diagnosed,
nephrotoxic- and uric acid-increasing drugs should
be avoided, and the dose of the medications should
be adjusted to the renal dysfunction if needed
21. Treatment
1- Fluid balance: vigorous hydration high
urine output.
Dose: 3 l/m2 every 24 h UOP > 100 ml/m2/h.
Balanced or isotonic solutions……. no
potassium is added to the hydration fluid.
Diuretics: If UOP remains low after achieving
optimal state of hydration
22. 2- Management of hyperuricaemia:
Rasburicase: the drug of choice at a dose of 0.2 mg/kg daily
given as a 30-minute infusion.
Allopurinol: only with G6PD deficiency or allergy to
rasburicase.
3- Management of hyperphosphataemia and hypocalcaemia.
Phosphate binders: given despite lack of studies that show
the efficacy.
Asymptomatic hypocalcaemia should not be treated ??
Symptomatic hypocalcaemia (arrhythmia, seizure or tetany)
calcium gluconate
4- Hyperkalaemia: Standard measures to reduce potassium
levels.
• Potassium ≥7 mmol/l dialysis is likely to be required
23. Renal replacement therapy
Severe oliguria
Anuria in the absence of hypovolaemia
Significant fluid overload
