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Tumor Lysis Syndrome (TLS) Risk Assessment Tool

This tool assesses the risk of tumor lysis syndrome (TLS) based on guidelines published by Cairo et al 2010 on behalf of the TLS expert panel (1).
1. Select tumor type:


Acute lymphoblastic leukaemia (ALL)


Acute myeloid leukemia (AML)


Anaplastic large cell lymphoma (ALCL)


Burkitt lymphoma/ leukemia


Chronic lymphocyctic leukemia (CLL)


Chronic myeloid leukemia (CML)


Diffuse large B cell lymphoma (DLBCL)


Hodgkin and low-grade NHL* Low grade NHL (Non Hodgkin Lymphoma) includes:

SLL (Small lymphocytic lymphoma)

Follicular lymphoma

Marginal zone B-cell lymphoma

MALT lymphoma

Mantle cell lymphoma (non-blastoid variant)

Cutaneous T-cell lymphoma


Other high grade lymphomas Includes:

Adult T cell lymphoma/leukemia (ATL)

Peripheral T cell lymphoma

Transformed lymphoma

Mantle cell lymphoma (blastoid variant)


Solid tumors and myeloma Most solid tumors and myeloma are low risk, with the exception of solid tumors which are sensitive to chemotherapy e.g. germ cell tumors, small cell lung cancers.


White blood cell (WBC) count:
< 100x109/L
≥100x109/L
LDH:
<2x ULN
≥2x ULN
Renal function:
Normal renal function
Renal dysfunction and/or involvement
Serum uric acid, phosphate or potassium> ULN:
No
Yes
White blood cell (WBC) count:
< 25x109/L
≥25 to < 100x109/L
≥100x109/L
LDH:
<2x ULN
≥2x ULN
Renal function:
Normal renal function
Renal dysfunction and/or involvement
Serum uric acid, phosphate or potassium> ULN:
No
Yes
Stage Early: Stage I or II disease.

Advanced: Stage III or IV disease

Stage I:
Nodal involvement in a single lymph node region OR a single localized extranodal site.

Stage II:
Nodal involvement in two or more lymph node regions OR localized extranodal involvement on one side of the diaphragm.

Stage III:
Nodal involvement or extranodal involvement on both sides of the diaphragm.

Stage IV:
Diffuse or disseminated involvement of one or more extralymphatic organs OR
involvement of liver, bone marrow, lungs, CNS.
Early
Advanced
LDH:
<2x ULN
≥2x ULN
Renal function:
Normal renal function
Renal dysfunction and/or involvement
Serum uric acid, phosphate or potassium> ULN:
No
Yes
Planned treatment:
Alkylating agent only Cyclophosphamide
Targeted and/ or biological therapies Fludarabine
Rituximab
BTK inhibitors: Ibrutinib, Acalabrutinib, Zanubrutinib
Venetoclax
Renal function:
Normal renal function
Renal dysfunction and/or involvement
Serum uric acid, phosphate or potassium> ULN:
No
Yes
Patient type:
Adult
Child
LDH:
Within normal range
>ULN
Bulky disease: A nodal mass >7.5cm.
No
Yes
Stage:
I or II
III or IV
LDH:
<2x ULN
≥2x ULN
Renal function:
Normal renal function
Renal dysfunction and/or involvement
Serum uric acid, phosphate or potassium> ULN:
No
Yes
Patient type:
Adult
Child
LDH:
Within normal range
>ULN
Bulky disease: A nodal mass >7.5cm.
No
Yes
Stage:
I or II
III or IV
LDH:
<2x ULN
≥2x ULN
Renal function:
Normal renal function
Renal dysfunction and/or involvement
Serum uric acid, phosphate or potassium> ULN:
No
Yes
Tumor type:
Myeloma and most solid tumors except bulky chemo-sensitive tumors listed below.
Bulky chemo-sensitive tumors e.g. neuroblastoma, germ cell, small cell lung cancer.
Renal function:
Normal renal function
Renal dysfunction and/or involvement
Serum uric acid, phosphate or potassium> ULN:
No
Yes
Patient type:
Adult
Child
Stage:
Stage I-II
Stage III-IV
Renal function:
Normal renal function
Renal dysfunction and/or involvement
Serum uric acid, phosphate or potassium> ULN:
No
Yes
TLS risk:

Tumor lysis syndrome (TLS) risk assessment tool/ calculator

Tumor lysis syndrome is a potentially life threatening complication that may develop after initiating systemic therapy in patients with high proliferative, typically (but not exclusively) hematological malignancies.

It results from rapid cell lysis and release of toxic metabolites (potassium, phosphate, nucleic acids) into the circulation. Nucleic acids are metabolised to uric acid (hyperuricemia) and released phosphate binds to calcium causing hypocalcemia. Uric acid and calcium-phosphate deposit in renal tubules causing acute kidney injury. Electrolyte disturbances can also lead to arrhythmias and seizures.

Laboratory features of TLS:
Elevated serum uric acid (25% increase)
Elevated serum potassium (25% increase)
Elevated serum phosphate(25% increase)
Decreased serum calcium (25% decrease)

TLS is most commonly associated with highly proliferative hematological malignancies e.g. Burkitt lymphoma and acute lymphoblastic leukaemia (ALL) after initiation of systemic therapy. However, it can also occur spontaneously or after commencing corticosteroids and it may also occur in other malignancies with a high proliferation rate.

Risk assessment is crucial in identifying patients at risk of TLS so that appropriate prophylaxis can be commenced prior to systemic therapy.

This risk assessment tool is based on the recommendations of an international expert panel published in 2010(1). The risk stratification takes into account the type of malignancy, tumor burden, planned treatment and renal function and stratifies patients as low, intermediate or high risk for developing TLS. The recommended prophylaxis is guided by the TLS risk status.

The risk of developing TLS according to risk status is estimated as:
Low risk: <1%
Intermediate risk: 1-5%
High risk: >5%

It should be noted that this TLS risk stratification algorithm has not been tested in a prospective trial, but is based on detailed literature review and expert consensus.

References:
  1. Cairo MS, Coiffier B, Reiter A, Younes A, Panel on behalf of the TLSE. Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. Br J Haematol. 2010;149(4):578-586. doi:https://doi.org/10.1111/j.1365-2141.2010.08143.x
  2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/rasbsan071202LB.pdf
  3. https://www.medicines.org.uk/emc/product/1316/smpc#gref