Tumor lysis syndrome resident survival guide
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Twinkle Singh, M.B.B.S. [2]
Definition
Tumor lysis syndrome (TLS) is a group of metabolic abnormalities resulting from rapid lysis of malignant cells and massive release of cell breakdown products into blood. It is a life threatening condition and an oncologic emergency. Metabolic complications include hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia and hyperuricosuria.
Causes
Life Threatening Causes
Tumor lysis syndrome resulting from any cause is a life threatening condition and needs immediate management.
Common Causes
Commonly tumor lysis syndrome is precipitated by chemotherapy in patients with hematologic malignancies.
- Burkitt's lymphoma
- Acute myeloid leukemia
- Acute lymphoblastic leukemia
- Chronic lymphocytic leukemia
- Chronic myeloid leukemia
- Non-Hodgkin's lymphoma
- Multiple myeloma
Classification
Cairo and Bishop classified and graded TLS as laboratory tumor lysis syndrome (LTLS) and clinical tumor lysis syndrome (CTLS).
Cairo and Bishop Definition for Laboratory Tumor Lysis Syndrome (LTLS)
LTLS is considered to be present if 2 or more of the following serum abnormalities are present within 3 days or 7 days after cytotoxic therapy.
| Element | Value | Change from baseline |
| Uric acid | ≥476 μmol/L or 8 mg/dL | 25 % increase |
| Potassium | ≥6 mmol/L or 6mg/L | 25 % increase |
| Phosphorus | ≥2.1 mmol/L for children ≥1.45 mmol/L for adults |
25 % increase |
| Calcium | ≤1.75 mmol/L | 25% decrease |
Cairo and Bishop Definition and Grading for Clinical Tumor Lysis Syndrome (CTLS)
Clinical tumor lysis syndrome is said to be present if LTLS is present plus 1 or more of the following clinical correlations:
| Complication | Grade | |||||
| 0 | 1 | 2 | 3 | 4 | 5 | |
| Creatinine | ≤1.5×ULN | 1.5×ULN | >1.5-3.0×ULN | >3-6×ULN | >6×ULN | Death |
| Cardiac arrhythmia | None | Intervention not indicated | Medical intervention indicated, but not urgently |
Controlled with a device or symptomatically and incompletely controlled medically |
Life threatening | Death |
| Seizure | None | - | One well controlled generalized seizure OR infrequent multiple focal motor seizures not affecting activities of daily living |
poorly controlled seizure disorder, seizure with altered consciousness |
Status epilepticus, intractable epilepsy |
Death |
ULN: Upper limit of normal
Modified LTLS and CTLS criteria by Howard et al
- CTLS is considered to be present in cases of any cardiac dysrhythmia, symptomatic hypocalcemia or acute kidney injury is present along with LTLS.
- LTLS is considered to be present if 2 or more of the following serum abnormalities are present during the same 24 hour period within 3 days or 7 days after cytotoxic therapy.
| Element | Value |
| Uric acid | ≥ 476 μmol/L or 8 mg/dL, > ULN for age in children |
| Potassium | ≥ 6 mmol/L or 6mg/L |
| Phosphorus | ≥ 2.1 mmol/L for children, ≥ 1.45 mmol/L for adults |
| Calcium | Corrected calcium ≤ 1.75 mmol/L or, ionized calcium < 0.3 mmol/L |
Prevention of TLS
Prevention of tumor lysis syndrome is of prime importance because once it is established, it is very difficult to treat and life threatening.
Shown below is an algorithm summarizing the approach to tumor lysis syndrome.
| Identify patients at risk of TLS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Low Risk Disease (LRD): ❑ Solid tumors | Intermediate Risk Disease (IRD): ❑ Bulky or advanced stage solid tumors ❑ Plasma cell leukemia ❑ Stage III/IV Non-Hodgkin's lymphoma with LDH > 2xULN ❑AML with WBC count ≤25,000 cells/μL and LDH > 2× ULN OR AML with WBC count 25,000-100,000 cells/μL ❑ CLL treated with fludarabine or rituximab or CML with WBC count > 50,000 cells/μL ❑ ALL with WBC < 100,000 cells/μL and LDH > 2xULN ❑ Burkitt's lymphoma stage I/II with LDH < 2x ULN ❑Lymphoblastic lymphoma stage I/II with LDH < 2x ULN | High Risk Disease (HRD): ❑ AML with WBC count > 100,000 cells/μL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
❑ Wait and watch approach with close monitoring ❑ Hydration | ❑ Laboratory tests monitoring ❑ Hydration ❑ Allopurinol administration ❑ ±Single dose of rasburicase in pediatric patients | ❑ ICU admission ❑ Nephrology consult ❑ Laboratory tests monitoring every 4-6 hours ❑ Hydration ❑ Delay tumor therapy (individual clinical judgement) ❑ Cardiac monitoring ❑ Rasburicase in pediatric patients | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||