Tumor Lysis

Syndrome
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 BACKGROUND

Tumor Lysis An oncological emergency, which can

Syndrome ultimately lead to death

■ May cause life-threatening acute kidney injury, arrhythmias, and neurologic

complications
■ It occurs most frequently after initiation of chemotherapy for hematological
neoplasms
■ Despite the low risk and scarcity of these tumors, following therapy, TLS is
more likely to develop, especially in gastric, lung, and breast cancer
patients

Infante, et al (2021); Howard (2019); Rahmani et al (2019)

TUMOR LYSIS SYNDROME

01. Definition &

05. Diagnosis &
Epidemiogy
Classification
02. Risk Factors &
06. Management
Etiology
07. Prognosis
03. Pathophysiology

04. Clinical
Manifestations
 DEFINITION EPIDEMIOLOGY
■ The prevalence varies among
different malignancies, used
■ A hemato-oncologic emergency anticancer therapies, and
■ Characterized by: prophylactic procedures
Hyperuricemia ■ Commonly associated with
Hyperkalemia hematological malignancies
Hyperphosphatemia
Hypocalcemia, and ■ The incidences of TLS in acute
Metabolic acidosis leukemia, NHL, and chronic
leukemia are 14%, 4%, and 2%,
respectively

Matuszkiewicz-Rowinska J dan Malyszko J (2020); Alakel et al., (2017); Hajjar, et al (2022); Belay, Yirdaw and Enawgaw (2017)
TUMOR LYSIS SYNDROME

01. Definition &

05. Diagnosis &
Epidemiogy
Classification
02. Risk Factors &
06. Management
Etiology
07. Prognosis
03. Pathophysiology

04. Clinical
Manifestations
 RISK FACTORS & ETIOLOGY
■ Hematologic malignancies:
Burkitt lymphoma, ALL, AML, acute lymphoblastic lymphoma, T cell
non-Hodgkin lymphoma, diffuse large B cell lymphoma
■ Solid tumors:
Lymphosarcoma; small cell lung cancer; metastatic medulloblastoma;
germ cell tumors; ovarian, prostate, pancreatic, brain, breast, kidney,
colon, rectum, liver, biliary tree cancers; soft tissue sarcoma; thymoma;
metastatic melanoma
■ Chemotherapy

Webster and Kaplow (2021)

 RISK FACTORS & ETIOLOGY

■ Hematologic malignancies, solid tumors

■ Advanced age
■ Pre-existing renal dysfunction (↑ Cr, ↓GFR, oliguria, anuria)
■ Elevated lactate dehydrogenase levels (2x ULN)
■ Increased uric acid levels
■ Cancer treatment modalities (chemotherapy, total body irradiation,
monoclonal antibodies, tyrosine kinase inhibitors, proteasome inhibitors,
chimeric antigen receptor T cells, proapoptotic agent, corticosteroids,
thiazide diuretics, levodopa, alcohol)

Webster and Kaplow (2021)

 Risk factors and diagnosis of Tumor Lysis Syndrome

Puri et al (2020)
 Durani and Hogan (2020)

Risk stratification of TLS by tumour type and disease burden

(A) Acute lymphoblastic leukemia (D) Aggressive lymphoma
(B) Acute myeloid leukemia (E) Indolent lymphoma
(C) Solid tumor (F) Chronic lymphocytic leukemia
Chronic myeloid leukemia and multiple myeloma are very rarely associated with
tumor lysis syndrome and thus not included.
TUMOR LYSIS SYNDROME

01. Definition &

05. Diagnosis &
Epidemiogy
Classification
02. Risk Factors &
06. Management
Etiology
07. Prognosis
03. Pathophysiology

04. Clinical
Manifestations
 PATHOPHYSIOLOGY
TLS occurs due to a burst of
tumor cells leading to a large
release of potassium, phosphate,
and nucleic acids into circulation

Significant amount of damage to

the systemic circulation of the
human body

Pathophysiology and clinical manifestations of Tumor Lysis Syndrome

Rahmani, et al (2019)
 Hyperuricemia High levels of
uric acid

■ The proximal renal tubules Precipitation of uric acid crystals

normally are responsible Micro-obstruction
for clearing uric acid
Reduced GFR
■ Humans lack the enzyme Higher vascular resistance in
to break down uric acid peritubular capillaries
into the much more soluble Increase the release of
compound allantoin proinflammatory cytokines
Increase use of nitric oxide (NO)
■ Kidneys can quickly
become saturated with
high levels of uric acid
kidney injury

Greguska C (2021)
 Hyperphosphatemia & Hypocalcemia
Hyperphosphatemia
■ Cancer cells may contain
up to 4x the phosphorus
concentration found in Phosphorus binds
normal cells extracellular calcium

■ High levels of Hypocalcemia

phosphorus in the Calcium phosphate
bloodstream  the body crystals in body tissues
attempts to compensate
with renal elimination
Worsen
kidney injury

Greguska C (2021)
 Hypekalemia

Intracellular potassium Patients with TLS

concentrations that can be
as high as 120 mEq/L are Normal condition
released from a lysing
The acute efflux of
tumor cell
potassium may
The liver, muscles, GI overwhelm normal
tract, and kidneys mechanisms
work together to
remove excess
potassium from the Systemic end-
body organ effects

Greguska C (2021)
TUMOR LYSIS SYNDROME

01. Definition &

05. Diagnosis &
Epidemiogy
Classification
02. Risk Factors &
06. Management
Etiology
07. Prognosis
03. Pathophysiology

04. Clinical
Manifestations
 CILINICAL MANIFESTATIONS
Laboratory finding Possible clinical manifestations

Hyperkalemia Cardiac dysrhythmia, muscle cramps, anorexia,

fatigue, paresthesias, sudden cardiac death

Hyperuricemia Hematuria, oliguria, anuria, edema, hypertension,

flank pain, lethargy, somnolence, AKI, and renal
failure
Hyperphosphatemia AKI, hypocalcemia, nausea, vomiting, lethargy,
seizures
Hypocalcemia Muscle cramps, paresthesias, tetany, cardiac
dysrhythmias, hypotension, hallucinations, altered
mental status, seizures

Greguska C (2021)
TUMOR LYSIS SYNDROME

01. Definition &

05. Diagnosis &
Epidemiogy
Classification
02. Risk Factors &
06. Management
Etiology
07. Prognosis
03. Pathophysiology

04. Clinical
Manifestations
 Cairo-Bishop Classification of Laboratory and Clinical Tumor Lysis
Syndrome

Halfdanarson, T.R., Hogan, W.J. and Madsen, B.E. (2017)

 Severity grading criteria for clinical TLS

Durani and Hogan (2020)

TUMOR LYSIS SYNDROME

01. Definition &

05. Diagnosis &
Epidemiogy
Classification
02. Risk Factors &
06. Management
Etiology
07. Prognosis
03. Pathophysiology

04. Clinical
Manifestations
 Algorithm to guide prophylaxis and treatment of tumor lysis syndrome
based on risk stratification

Sury (2019)
 Preventive strategies
■ Close monitoring for patients at high risk of developing TLS or suffering
from TLS, during the first 48-72 hours of chemotherapy:
- Serum electrolyte levels
- Uric acid
- Creatinine and urea nitrogen
(every 4-6 hours)
■ Correct hypovolemia if present
■ Avoid the administration of nephrotoxic drugs and agents able to block
the tubular reabsorption of uric acid
■ Potassium and phosphorus should be eliminated from the diet and
intravenous (IV) fluids

Attinà, Tepedino and Ruggiero (2021); Mirrakhimov et al. (2015)

 Hyperhydration
■ Hydration is recommended for all patients at risk of TLS
■ Hydration should start immediately following the patient’s admittance to
the ward and continued up to 2-3 days after chemotherapy (contain no
potassium, calcium and phosphate)
■ Dose: ≥ 3 L/m2/day (200 ml/kg/day in children up to a weigh of 10 kg)
■ Maintain a urinary flow of 100 ml/m2/hour (3 ml/kg/hour in children ≤
10 kg), with a specific urine weight at ≤1,010
■ In patients without acute obstructive uropathy and/or hypovolemia,
diuretics may also be required (mannitol with a dose of 0,5mg/kg or
furosemide with a dose of 0,5-1 mg/kg)

Attinà, Tepedino and Ruggiero (2021)

 Alkalinization of urine

■ Alkaline urine facilitates the excretion of uric acid released during TLS
■ It is controversial for two reasons:
- Alkaline urinary pH promotes precipitation of calcium phosphate at
the renal level and other organs  ↑ risk of renal insufficiency
- Alkalinization also significantly reduces the solubility of xanthine,
facilitating the formation and precipitation of xanthine crystals 
↑ risk of kidney failure

Attinà, Tepedino and Ruggiero (2021)

 Hyperuricemia

■ Allopurinol is an analogue of xanthine which prevents the formation of

uric acid through the inhibition of xanthine oxidase
Recommended dose: 200-400 mg/m2/day in adult patients, 200 mg/
m2/day in children, divided in 1-3 doses, maximum dose: 600 mg/day

■ Rasburicase catalyzes enzymatic oxidation of uric acid to allantoin (5-

10 times more soluble than uric acid at urinary level)
Recommended dose: 0.2 mg/kg/day, once a day by IV infusion of 30
minutes in 50 ml of 0.9% NaCl solution
Duration of treatment: 5-7 days

Attinà, Tepedino and Ruggiero (2021)

 Hyperkalemia

■ Hyperkalemia can cause life-

threatening symptoms  emergent
hemodialysis is appropriate
■ In the absence of severe symptoms,
management of hyperkalemia is based
on whether the patient can produce
urine and whether they can safely
tolerate volume expansion

Sury (2019)
 Hyperphosphatemia & hypocalcemia
■ Administration of IV fluids increases
renal perfusion, glomerular filtration,
and urine output  ↑ phosphaturia
■ If fluids are not an option,
management should focus on
preventing further increases in serum
phosphorus levels  restrict dietary
phosphorus and utilizing oral
phosphate binders
■ Any additional calcium will likely be
chelated  ↑ calcium phosphate
deposition
Sury (2019)
 Hemodialysis &
renal replacement therapy

■ If intermittent hemodialysis is utilized for extracorporeal

clearance, rebound hyperkalemia or hyperphosphatemia might develop
 continuous renal replacement therapy is the best modality for solute
removal
■ For life-threatening hyperkalemia, early hemodialysis is recommended
■ For severe hyperphosphatemia, continuous renal replacement therapy
might also be the best treatment modality

Sury (2019)
TUMOR LYSIS SYNDROME

01. Definition &

05. Diagnosis &
Epidemiogy
Classification
02. Risk Factors &
06. Management
Etiology
07. Prognosis
03. Pathophysiology

04. Clinical
Manifestations
 PROGNOSIS

■ Life threatening

■ When not recognized early enough and aggressively treated, it is linked to a

significantly increased risk for poor outcomes

■ Overall in-hospital mortality ranging in different series from 21 to 32%

■ The highest reported rates in AML patients during induction therapy: 79%

Matuszkiewicz-Rowinska dan Malyszko (2020)

 CONLUSION

1. TLS is a hemato-oncological emergency, characterized by

hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and
metabolic acidosis
2. TLS is often associated with haematological malignancies due to high
rates of cell turnover and sensitivity to cytotoxic therapy
3. The clinical manifestations of TLS generally occur 12–72 hours after the
initiation of chemotherapy
4. Measures used for the prevention and treatment of TLS include IV
hydration, urine alkalinization, hypouricemic agents (allopurinol and
rasburicase), correction of electrolyte abnormalities and HD/RRT
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