Tumor lysis syndrome is a critical medical condition that results from the breakdown of cancer cells in your body. It leads to several metabolic complications and organ failure. It is common in people who have highly malignant cancers and respond well to chemotherapy.
What is Tumor Lysis Syndrome?
Tumor lysis syndrome is a condition that results from the extensive breakdown of any neoplasm in your body. When tumor cells break, they release cell substances, electrolytes, and nucleic acids into your body. This results in various problems, including metabolic issues (like electrolyte imbalance), cardiac arrhythmias, acute kidney injury, and other issues. It mostly occurs after chemotherapy. It is most common in people with different hematogenous (blood-related) cancers.
Incidence of Tumor Lysis Syndrome
The incidence of tumour lysis syndrome was 42 percent according to a study performed on people having non-Hodgkin lymphoma. However, only 6 percent of these cases were clinically significant.
Causes of Tumor Lysis Syndrome
Chemotherapy:
Tumor lysis syndrome is associated with malignancies. It is common in people undergoing chemotherapy. Medicines leading to tumor lysis syndrome include bortezomib, paclitaxel, hydroxyurea, rituximab, thalidomide, and etoposide. For tumour lysis syndrome to occur in such a condition, the tumor must be malignant and respond well to chemotherapy. According to the tendency to develop this syndrome, the doctors classify the causative tumors into three types:
High Risk Tumors
- Advanced Burkitt lymphoma
- Acute lymphoblastic leukemia (ALL) with a leukocyte (white blood cells) count of more than one lac cells per microliter (100,000/µL) or lactate dehydrogenase (LDH) levels twice the normal value.
- Acute myeloblastic leukemia (AML) with white blood cells more than one lac per micro litre.
- Diffuse large B-cell lymphoma with lactate dehydrogenase levels twice the normal value or lymphoma with bulky disease.
Intermediate Risk Tumors
- Acute lymphoblastic leukemia with white blood cells less than 100,000 per microlitre (<100,000/µL) or lactate dehydrogenase levels less than twice of normal value.
- Acute myeloblastic lymphoma with white cells ranging from 25,000 to 100,000 per microlitre.
- Diffuse beta-cell lymphoma without bulky disease and lactate dehydrogenase levels twice the normal value.
- Burkitt lymphoma with lactate dehydrogenase levels less than twice the normal value.
Low Risk Tumors
- Multiple myeloma
- Chronic lymphocytic leukemia (CLL)
- Solid Tumors
- Chronic myeloid leukemia (CML
Other Drugs Causing Tumor Lysis Syndrome:
Other drugs causing this syndrome include steroids, monoclonal antibodies (like rituximab, alemtuzumab, and cetuximab), and immune modulators (like nivolumab, pembrolizumab, interferon Alfa, and pomalyst).
Tumour Lysis Syndrome before Chemotherapy:
Although tumor lysis syndrome most often occurs after chemotherapy, it can also occur spontaneously before treatment in some highly aggressive tumors, such as Burkitt lymphoma, acute leukemia, and advanced non-Hodgkin lymphoma.
Symptoms Of Tumor Lysis Syndrome
Symptoms of this syndrome occur due to electrolyte imbalance and organ failure. Main symptoms include:
- Weakness
- Paralysis
- Lethargy
- Edema
- Fluid overload
- Seizures
- Malaise
- Difficulty to breath
- Irritability
- Nausea
- Vomiting
- Metallic taste
- Itching
- Joint pain
- Abdominal pain
- Muscle cramps
How is Tumor Lysis Syndrome Diagnosed?
Edema, malaise, weakness, paralysis, lethargy, and fluid overload are signs of tumor lysis syndrome.
History:
For the diagnosis, your doctor may ask questions like:
- Since when have you been feeling these symptoms after the diagnosis of your tumor? Do these symptoms arise after chemotherapy? What is the onset of these symptoms relative to chemotherapy?
- Do you feel symptoms like abdominal pain, abdominal distension, vomiting, nausea, joint pain, bad taste, seizures, weight loss, decreased appetite, and blood in urine?
- Do you experience symptoms like muscle cramps, swelling of the body, and flank pain?
Examination:
After a complete history, your doctor performs a complete general physical examination. While examining you, they focus on electrolyte imbalance, fluid overload, and organ failure findings. Key points to focus on are:
- Carpal spasm (spasm of the muscles of the hands and forearm)
- Pedal spasm (spasm of muscles of the feet and toes)
- Wheezing
- Chest auscultation shows muffled heart sounds
- Trousseau sign (your doctor inflates the blood pressure apparatus cuff above the systolic pressure for a few minutes, and it causes spasm in your hand or forearm. This test indicates Hypocalcemia)
- Pruritus
- Gangrene
- Edema
- Chvostek sign (Your doctor taps your facial nerve in front of your ear; if you have hypocalcemia, twitching or spasm occurs)
Investigations:
Complete Blood Count (CBC)
Complete blood count is an important investigation in tumor lysis syndrome. It may show leukocytosis (increased white blood cell count), anemia, and thrombocytopenia (decreased platelets).
Serum Electrolytes & Renal Parameters
In tumor lysis syndrome, serum electrolytes are deranged. There may be hypocalcemia (decreased calcium), hyperkalemia (increased potassium), hyperuricemia (increased uric acid), and hyperphosphatemia (increased levels of phosphate). Additionally, elevated blood urea nitrogen (BUN), lactate dehydrogenase, and creatinine levels may also be present.
Complete Urine Analysis (CUE)
Complete urine analysis (CUE) is essential in diagnosing tumor lysis syndrome. Your doctor checks the specific gravity, pH, and uric acid levels in urine twice or thrice daily before and after chemotherapy.
Electrocardiography (ECG)
Your doctor may advise electrocardiography (ECG) to detect cardiac function. Electrocardiography shows changes due to hyperkalemia, hypocalcemia, and other electrolyte abnormalities. Hyperkalemia, hypocalcemia, and hyperphosphatemia lead to severe cardiac arrhythmias (abnormal heart rhythm) that can even lead to sudden death. So, electrocardiography (ECG) monitoring twice or thrice a day is essential while managing tumor lysis syndrome.
Computed Tomography (CT) Imaging
Computed Tomography (CT) imaging is important in diagnosing tumors that cause tumor lysis syndrome. A CT scan of the chest, abdomen, and brain is helpful in diagnosing tumors in these areas.
Ultrasound
Your doctor may advise an abdominal ultrasound to locate tumors in your abdomen or retroperitoneum.
Diagnostic Criteria for Tumor Lysis Syndrome
Diagnosis is based on the criteria introduced by Cairo and Bishop. It helps to diagnose tumor lysis syndrome three days before and seven days after initiation of chemotherapy. Moreover, it also helps in determining the severity.
Your doctors diagnose tumor lysis syndrome if there are two or more of these criteria for 24 hours, three days before, and seven days after chemotherapy:
Laboratory Diagnostic Criteria:
According to this criterion, two of these symptoms are present for twenty-four hours in three days before and seven days after initiation of chemotherapy:
- Your serum calcium decreases by more than 25 percent from baseline or by less than 7 milligrams per deciliter (<7 mg/dL)
- Your serum uric acid increases by more than 25 percent from baseline or a value greater than 8 milligrams per deciliter (>8 mg/dL)
- Phosphorus levels increase by 25 percent from baseline or a value greater than 4.5 milligrams per deciliter (>4.5 mg/dL)
- Your serum potassium value is more than 25 percent from baseline or a value greater than 6 milliequivalents per liter (>6 mEq/L)
Clinical Diagnostic Criteria:
Clinical diagnostic criteria indicate the presence of tumor lysis syndrome along with one of the following:
- Creatinine levels are 1.5 times greater than the upper reference limit
- Cardiac arrhythmias
- Seizures
However, this diagnostic criterion by Cairo and Bishop is only helpful for cases that are on chemotherapy, but tumor lysis syndrome can also occur before chemotherapy. In addition to that, it is not helpful for patients with chronic kidney disease due to already elevated levels of creatinine.
Management Of Tumor Lysis Syndrome
Monitoring:
The doctors closely monitor patients with tumor lysis syndrome before and after chemotherapy. They perform electrocardiography and check serum electrolytes, serum uric acid, serum creatinine, fluid intake, and urine output regularly. Close monitoring is important to detect and treat complications as early as possible.
Hydration:
Aggressive intravenous hydration is the first step in managing tumor lysis syndrome.
If you are a high-risk case, your doctor gives you intravenous fluids before initiation of chemotherapy. Hydration aims to improve your renal perfusion. Moreover, your doctors advise crystalloids for volume expansion.
The doctor maintains hydration status before chemotherapy.
However, if you have renal or cardiac disease, your doctor will give you fluids carefully to prevent fluid overload. Hydration fluids are free of potassium or other electrolytes to prevent electrolyte imbalance.
Allopurinol & Febuxtat:
Your doctor may prescribe drugs like allopurinol and febuxostat to treat hyperuricemia. These drugs prevent the formation of uric acid and prevent obstructive uropathy.
Rasburicase:
Doctors prescribe rasburicase over allopurinol for patients with cardiac or renal impairment. Rasburicase reduces uric acid levels by catalyzing their breakdown, while allopurinol only reduces uric acid formation.
Correction of Electrolyte Abnormalities:
Correction of electrolyte abnormalities is important during the management of this syndrome.
Hyperkalemia
To correct hyperkalemia (an increase in potassium levels), your doctor may advise you to take a low-potassium diet, monitor potassium levels regularly, and give you potassium-lowering agents if it does not settle. Correcting hyperkalemia is important to prevent cardiac arrhythmias and other cardiac abnormalities.
Hyperphosphatemia
For hyperphosphatemia (an increase in phosphate levels), your doctor ensures excessive hydration and prescribes phosphate-binding drugs. Additionally, they can even undergo dialysis.
Hypocalcemia
Your doctor advises you to take calcium-containing foods and supplements, such as calcium chloride and calcium oxalate, to correct hypocalcemia.
Hemodialysis:
If you have excessive levels of potassium, phosphate, and uric acid in your body due to acute kidney injury in tumor lysis syndrome, your doctors will do haemodialysis. In acute kidney injury, you have symptoms like decreased or no urine output, fluid overload, and electrolyte imbalance (increased levels of potassium, phosphate, calcium, uric acid, and creatinine in your body).
During dialysis, your doctors keep giving replacement fluid at the same flow rate as dialysis. It helps to prevent electrolyte abnormalities like a rebound increase in potassium or phosphate.
Doctors prefer hemodialysis because peritoneal dialysis is ineffective in clearing potassium, phosphate, uric acid, and other metabolites.
Complications of Tumor Lysis Syndrome
This syndrome can result in serious complications. It can even lead to organ failure and death.
Electrolyte Imbalance:
Tumor lysis syndrome results in severe electrolyte imbalance, such as hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and raised levels of creatinine. These abnormalities cause various complications, like:
Hyperkalemia
It causes cardiac arrhythmias, muscle weakness, and paralysis. Cardiac arrhythmias can lead to sudden death.
Hypocalcemia
Hypocalcemia causes muscle weakness, spasms, twitching, cardiac arrhythmias, and tetany (characterized by weakness, spasms, and twitching of muscles).
Hyperphosphatemia
Hyperphosphatemia (an increase in phosphate levels in your body) causes hypocalcemia by binding calcium. Additionally, it causes kidney damage.
Hyperuricemia
It causes acute kidney injury and renal failure.
Cardiac Complications:
Tumor lysis syndrome can lead to severe cardiac complications, such as arrhythmias and cardiac arrest, which can cause sudden death. The causes of these complications are hyperkalemia, hypocalcemia, and hyperphosphatemia. Electrocardiograph (ECG) changes include tall, peaked T waves, wide QRS complexes, and a prolonged QT interval. Daily monitoring of cardiac function is important.
Seizures:
Electrolyte imbalance in tumor lysis syndrome can cause seizures. It is a life-threatening condition that can cause death.
Acute Kidney Injury:
Electrolyte imbalance in tumor lysis syndrome leads to acute kidney injury. Causes of acute kidney injury are:
- Uropathy
- Calcium crystal deposition in your kidneys
- Increased levels of potassium can damage your kidneys
- Hypovolemia
Management of acute kidney injury is important, and it includes controlled hydration, correction of electrolyte imbalance, decreasing uric acid levels, and dialysis.
Multi-Organ Failure:
Multi-organ failure is a severe complication of tumor lysis syndrome. Its causes include electrolyte imbalance, uropathy, and cytokine release. Organs affected in this condition include kidneys (acute kidney injury, renal failure, and permanent kidney damage), lungs (acute respiratory distress syndrome (ARDS) and respiratory failure due to pulmonary edema), heart (cardiac arrest, cardiac arrhythmias, and heart failure), and liver (liver dysfunction and failure). Early recognition, close monitoring, and immediate treatment of complications are important to prevent multi-organ failure. Moreover, dialysis and ventilatory support might be needed in this condition.
How to Prevent Tumor Lysis Syndrome?
Early identification of the risk factors is essential for the prevention of tumor lysis syndrome. Your doctor suspects tumor lysis syndrome early on the basis of the type of tumor and its burden. If it is a high-risk tumor and they are planning chemotherapy, they ensure these steps for the prevention of this syndrome:
- Your doctors keep on monitoring your cardiac function (by electrocardiography).
- They monitor your renal parameters, serum electrolytes, uric acid, creatinine, urine output, and hydration status.
- They keep you well hydrated to prevent hypovolemia and acute kidney injury.
- In addition, if they notice hypocalcemia, they replace calcium to prevent tetany, muscle spasms, and seizures.
- If they notice symptoms related to hyperkalemia (increased potassium levels), they manage it early.
- They give you medicines like allopurinol, resburicase, and febuxostat while giving chemotherapy to reduce uric acid levels and prevent uric acid-related complications as a result.
Conclusion
Tumor lysis syndrome is a critical medical condition that results from the breakdown of cancer cells in your body. It mostly occurs after initiation of chemotherapy. Its symptoms include nausea, vomiting, joint pain, diarrhea, seizures, cardiac arrest, cardiac arrhythmias, and severe electrolyte imbalance. Early detection and treatment are important and life-saving.
References
[1] Ahmed, Z., Barefah, A., Wasi, P., Jones, G., & Ramsay, J. (2019). Tumour lysis syndrome in a patient with undifferentiated endometrial stromal sarcoma. Gynecologic oncology reports, 28, 41–43. https://doi.org/10.1016/j.gore.2019.02.006
[2] Hande, K. R., & Garrow, G. C. (1993). Acute tumor lysis syndrome in patients with high-grade non-Hodgkin’s lymphoma. The American journal of medicine, 94(2), 133–139.
[3] Montesinos, P., Lorenzo, I., Martín, G., Sanz, J., Pérez-Sirvent, M. L., Martínez, D., Ortí, G., Algarra, L., Martínez, J., Moscardó, F., de la Rubia, J., Jarque, I., Sanz, G., & Sanz, M. A. (2008). Tumor lysis syndrome in patients with acute myeloid leukemia: identification of risk factors and development of a predictive model. Haematologica, 93(1), 67–74. https://doi.org/10.3324/haematol.11575
[4] Malik, I. A., Abubakar, S., Alam, F., & Khan, A. (1994). Dexamethasone-induced tumor lysis syndrome in high-grade non-Hodgkin’s lymphoma. Southern medical journal, 87(3), 409–411. https://doi.org/10.1097/00007611-199403000-00024
[5] Cairo, M. S., & Bishop, M. (2004). Tumour lysis syndrome: new therapeutic strategies and classification. British journal of haematology, 127(1), 3–11. https://doi.org/10.1111/j.1365-2141.2004.05094.x
[6] KRAKOFF, I. H., & MEYER, R. L. (1965). PREVENTION OF HYPERURICEMIA IN LEUKEMIA AND LYMPHOMA: USE OF ALOPURINOL, A XANTHINE OXIDASE INHIBITOR. JAMA, 193, 1–6. https://doi.org/10.1001/jama.1965.03090010007001
[7] Abdel-Nabey, M., Chaba, A., Serre, J., Lengliné, E., Azoulay, E., Darmon, M., & Zafrani, L. (2022). Tumor lysis syndrome, acute kidney injury, and disease-free survival in critically ill patients requiring urgent chemotherapy. Annals of intensive care, 12(1), 15.
[8] Cairo, M. S., Coiffier, B., Reiter, A., Younes, A., & TLS Expert Panel (2010). 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. British journal of haematology, 149(4), 578–586.