11/14/24, 10\:39 AM Tumour Lysis Syndrome

Tumour Lysis Syndrome

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Tumour lysis syndrome (TLS)\: oncological emergency due to rapid breakdown of malignant cells, leading to signi
electrolyte imbalances; common in lymphoproliferative malignancies post-treatment.
Common triggers\: initiation of chemotherapy (especially cell cycle phase-speci
therapy, and radiotherapy; occurs 12-72 hours post-treatment.
Pathophysiology\: rapid cell breakdown releases intracellular contents (uric acid, phosphate, potassium) overwhelming
homeostasis, causing hyperuricaemia, hyperphosphataemia, hypocalcaemia, and hyperkalaemia.
Risk factors\: poorly di
growing solid tumours (hepatocellular carcinoma, small cell lung cancer, breast cancer), age, large tumour burden, high
LDH, extensive bone marrow involvement, pre-existing renal impairment, dehydration, nephrotoxic agents.
Symptoms\: vague and non-speci
output, syncope, chest pain, palpitations.
Examination
tachycardia;
Investigations\: ECG (arrhythmias), urine pH (uric acid crystals), FBC (leukocytosis), U&Es (renal impairment, electrolyte
abnormalities), bone pro
Diagnosis\: laboratory TLS (two or more\: uric acid ≥476 micromol/L, potassium ≥6 mmol/L, phosphate ≥1.45 mmol/L,
calcium ≤1.75 mmol/L) and clinical TLS (lab TLS plus creatinine ≥1.5x upper limit, arrhythmia, seizure, sudden death).
Risk strati
Low risk\: regular blood tests,
Intermediate risk\: blood tests 1-2 times daily, IV hydration, allopurinol or rasburicase for hyperuricaemia.
High risk\: blood tests 3-4 times daily, IV hydration, rasburicase for hyperuricaemia.
Management of TLS\:
General\: IV
Electrolyte management\:
Hyperuricaemia\: IV rasburicase.
Hyperkalaemia\: calcium gluconate, glucose/insulin infusion.
Hyperphosphataemia\: phosphate binders (rarely used).
Hypocalcaemia\: IV calcium gluconate for symptomatic cases, anticonvulsants for seizures.
Complications\: acute kidney injury, cardiac arrhythmias, seizures, lactic acidosis.
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Introduction

Tumour lysis syndrome (TLS) is an oncological emergency that occurs when malignant cells rapidly break down,
releasing their contents into the bloodstream. This causes signi
and can be life-threatening if not recognised and treated.
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It most commonly occurs in patients with lymphoproliferative malignancies after initiation of treatment.

Aetiology

TLS most commonly occurs after the initiation of chemotherapy, particularly in regimes that include cell cycle phase-
speci
1
It typically occurs between 12-72 hours after treatment is given. TLS has also been known to occur with other treatments
such as corticosteroids, hormonal therapy and radiotherapy, but this is less common.
Cancer cells typically have a high turnover rate, producing large amounts of nucleic acids (broken down to uric acid) and
phosphate. When chemotherapy is started, these cells can break down rapidly, releasing the intracellular contents,
which quickly overwhelm the body's normal homeostatic response.
This release results in several metabolic and electrolyte abnormalities\:
Hyperuricaemia
Hyperphosphataemia
Hypocalcaemia (secondary to hyperphosphataemia)
Hyperkalaemia
Spontaneous TLS can also occur, particularly in high-grade haematological malignancies, which naturally have a very
high cell turnover rate, but this is rare.

Risk factors

Patients with certain malignancies are more at risk of TLS\:
2
Poorly di
Leukaemia\: particularly acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) and transformed chronic
myeloid leukaemia (CML)
Fast-growing solid tumours (e.g. hepatocellular carcinoma, small cell lung cancer, breast cancer)
Other risk factors include\:
2
Age
Large tumour burden
LDH >1,500 IU
Extensive bone marrow involvement
High tumour sensitivity to chemotherapy
Speci
interferon, corticosteroids, tamoxifen)
Pre-existing renal impairment
Dehydration
Concurrent use of nephrotoxic agents

Clinical features

History

Symptoms of TLS are vague and non-speci
electrolyte disturbances found in TLS\:
Nausea and vomiting
Confusion
Muscle cramps and tetany
Diarrhoea
Lethargy
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Reduced urine output
Syncope
Chest pain
Palpitations
The history may identify risk factors for TLS.

Clinical examination

There are no speci
electrolyte disturbances\:
Lymphadenopathy\: due to the underlying malignancy
Splenomegaly\: due to the underlying malignancy
Peripheral oedema\: due to renal failure
Trousseau's sign\: due to hypocalcaemia
Chovstek's sign\: due to hypocalcaemia
Tachycardia\: due to cardiac arrhythmias

Investigations

Investigations are used to diagnose TLS and assess for complications. Investigations are also used to monitor patients at
risk of TLS, especially before or during treatment.

Bedside investigations

Relevant bedside investigations include\:
ECG\: performed if hyperkalaemia, hyperphosphataemia or hypocalcaemia develop to check for arrhythmias
Urine pH\: performed in the presence of hyperuricaemia; if urine pH \< 5, there is an increased risk of precipitation of uric
acid crystals, which may cause obstruction

Laboratory investigations

Relevant laboratory investigations include\:
Full blood count\: patients with leukocytosis are at increased risk of TLS as it correlates with tumour burden
Urea & electrolytes\: to identify renal impairment and electrolyte abnormalities (e.g. hyperkalaemia)
Bone pro\: to identify hyperphosphataemia and hypocalcaemia.
Uric acid\: raised uric acid is a risk factor for developing TLS and a feature of TLS (hyperuricemia)
LDH\: raised LDH is a risk factor for TLS.

Diagnosis

There are two sets of diagnostic criteria for TLS\: laboratory TLS and clinical TLS.
Laboratory TLS is de
cancer treatment\:
Uric acid ≥476 micromol/L (≥8 mg/dL) or 25% increase from baseline
Potassium ≥6 mmol/L or 25% increase from baseline
Phosphate ≥1.45 mmol/L or 25% increase from baseline
Calcium ≤1.75 mmol/L or 25% decrease from baseline
Clinical TLS is diagnosed in patients who meet the criteria for laboratory TLS and at least one of the following\:
Increase in serum creatinine ≥1.5 times the upper limit of normal
Cardiac arrhythmia
Seizure
Sudden death
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Management

Risk strati

Risk strati
measures can be implemented.
The aim is to prevent TLS from developing and identify patients with TLS early so appropriate management can be
started.
Table 1. Risk strati
Low risk Intermediate risk High risk
Solid tumours
Early-stage Burkitt’s
lymphoma, with LDH \< 2
times the upper limit of
normal
Certain high-grade non-
Hodgkin’s lymphoma (e.g.
di
lymphoma)
Chronic leukaemias
Early-stage
lymphoblastic lymphoma
with LDH \< 2 times the
upper limit of normal
ALL with WCC > 100 x
9
10 /L OR WCC \< 100 x
9
10 /L and LDH > 2 times
the upper limit of normal
Multiple myeloma
ALL with WCC \< 100 x
9
10 /L and LDH \< 2 times
the upper limit of normal
AML with WCC > 100 x
9
10 /L
Hodgkin’s lymphoma
9
AML with WCC 25 x 10 /L
9
– 100 x 10 /L OR WCC \<
9
25 x 10 /L and LDH > 2
times the upper limit of
normal
Low proliferating non-
Hodgkin’s lymphoma
CLL with WCC >50 x
9
10 /L and/or treated with

agents
After a patient's level of risk has been established, preventative measures can be implemented.
Low risk
Regular monitoring of blood tests (U&Es, bone pro
Monitor
Consider allopurinol if hyperuricaemia is present before starting chemotherapy treatment (300mg for 7 days, to start 2
days before chemotherapy treatment)
Intermediate risk
Regular monitoring of blood tests (U&Es, bone pro
treatment and daily after that
Intravenous hydration with normal saline for two days before treatment (aim to maintain urine output 100 mL/m²/hour)
Allopurinol should be given to patients with hyperuricemia; if allopurinol does not reduce serum uric acid, consider
rasburicase
High risk
Regular monitoring of blood tests (U&Es, bone pro
Intravenous hydration with normal saline for two days before treatment (aim to maintain urine output 100 mL/m²/hour)
Rasburicase should be given to patients with hyperuricaemia
Management of TLS3
If TLS develops, then early recognition and escalation of management are essential. Early liaison with intensive care is
required, as patients may require renal replacement therapy.
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General management of TLS includes\:
Intravenous
Observations should be monitored at least 4-6 hourly, including
Daily weights
Blood tests every 6 hours after diagnosis of TLS
ECG at baseline, consider cardiac monitor if hyperkalaemia/hypocalcaemia
Management of electrolyte abnormalities includes\:
Hyperuricaemia\: intravenous rasburicase for 3-7 days (use maximum dose allopurinol if rasburicase contraindicated)
Hyperkalaemia\: calcium gluconate for cardiac protection, followed by a glucose/insulin infusion
Hyperphosphataemia\: phosphate-binding agents can be considered but are rarely used
Hypocalcaemia\: symptomatic hypocalcaemia should be treated with IV calcium gluconate; seizures can be managed
with anticonvulsant medication according to local guidelines

Complications

Complications of TLS include\:
Acute kidney injury\: due to calcium phosphate deposition and uric acid
Cardiac arrhythmias\: due to hyperkalaemia and/or hypocalcaemia
Seizures\: due to hypocalcaemia and/or hyperphosphataemia
Lactic acidosis\: due to chemotherapy-induced cell death and AKI

References

BMJ Best Practice. T u m o u r L y s i s S y n d r o m e . Published 2023. Available from\: [LINK]
Life in The Fast Lane. T u m o u r L y s i s S y n d r o m e . Published 2020. Available from\: [LINK]
British Journal of Haematology. G u i d e l i n e s f o r t h e m a n a g e m e n t o f t u m o u r l y s i s s y n d r o m e i n a d u l t s a n d c h i l d r e n w i t h
h a e m a t o l o g i c a l m a l i g n a n c i e s o n b e h a l f o f t h e B r i t i s h C o m m i t t e e f o r S t a n d a r d s i n H a e m a t o l o g y . Published 2015. Available
from\: [LINK]

Related notes

Anal Cancer and Anal Intraepithelial Neoplasia (AIN)
Brain Tumours
Breast Cancer
Hypercalcaemia of Malignancy
Laryngeal Cancer

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Contents

Introduction
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Aetiology
Risk factors
Clinical features
Investigations
Diagnosis
Source\: geekymedics.com
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