TLS causes development of conditions such as hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia and hyperuricosuria. The signs and symptoms experienced during TLS occur due to these conditions. The following are the signs and symptoms:

• Severe muscular weakness
• Cardiac abnormalities
• Tetany
• Myopathy
• Parkinsonian
• Sudden onset of mental incapacity
• Papilledema
• Paralysis

• Hodgkin Lymphoma

  Acute tumor lysis syndrome in patients with high-grade non-Hodgkin’s lymphoma. Am J Med. 1993;94(2):133-9. Burghi G, Berrutti D, Manzanares W. Síndrome de lisis tumoral en terapia intensiva: encare diagnóstico y terapéutico. [revista.acho.info]

  We retrospectively evaluated the efficacy of febuxostat 10 mg in prevention of hyperuricemia associated with TLS (HU-TLS) in 12 patients with non-Hodgkin's lymphoma (NHL). Mean UA levels were found to significantly decrease (p = 0.003). [ncbi.nlm.nih.gov]

  TLS management varied by region: 11% of patients in Virginia received uric acid lowering therapy vs 26% in South Carolina (p<0.001) and lymphoma subtype: 11% Hodgkin lymphoma, 26% B-cell non-Hodgkin lymphomas, p<0.001). [ashpublications.org]

• Anemia

  METHODS: We developed an index called the rapid anemia progression index, which represents the duration and progression of anemia, to evaluate risk factors for tumor-lysis syndrome. [ncbi.nlm.nih.gov]

  Aplastic anemia https://www.youtube.com/watch?v=OlAMq... Acute kidney injury https://www.youtube.com/watch?v=73QwS... [youtube.com]

• Fever

  A 21-year-old woman who presented with pelvic mass, fever and cough was admitted. Ultrasonography revealed a large solid mass and serum CA125 was increased. [ncbi.nlm.nih.gov]

  Vasculitis: Causes, clinical features and management https://youtu.be/lCLK7RWlJts Dengue fever: clinical features and management https://youtu.be/VNQV8KgT3-Q Addison’s disease https://youtu.be/JVKycyaSvIk Hepatopulmonary syndrome https://youtu.be/uu50uWjR-rg [youtube.com]

  Tell your healthcare provider right away if you have a fever or any signs of an infection during treatment with VENCLEXTA. [venclexta.com]

  Formerly known as Familial Hibernian fever, Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) is a rare, genetic disease that causes recurrent episodes of fever that typically last more than one week and are associated with chills and [rheumatology.org]

  It comprises of a constellation of fever, nausea/vomiting, and pain. [radiopaedia.org]

• Swelling

  […] become swollen 腫れ 【はれ】 swelling, boil 腫れる 【はれる】 to swell (from inflammation), to become swollen 腫らす 【はらす】 to cause to swell, to inflame 腫れ物 【はれもの】 tumor, tumour, swelling, boil, abscess 腫れ物に触るように 【はれものにさわるように】 with great caution, gingerly Readings Chinese [jisho.org]

  […] tumor [ too´mor ] 1. swelling or morbid enlargement; this is one of the cardinal signs of inflammation. 2. a new growth of tissue in which cell multiplication is uncontrolled and progressive. [medical-dictionary.thefreedictionary.com]

  […] most common side effects of VENCLEXTA when used alone in people with CLL/SLL include low white blood cell counts; diarrhea; nausea; upper respiratory tract infection; low red blood cell counts; tiredness; low platelet counts; muscle and joint pain; swelling [venclexta.com]

  The fluid then builds up in the body causing edema (swelling) and in extreme cases heart failure. Hypouricemic Medication – These medications cause your body to make less uric acid, which then prevents hyperuricemia. [oncolink.org]

  Arm swelling is another common symptom of SVC syndrome. [pulmccm.org]

• Common Cold

  […] medication Adverse reaction to anti-common cold drugs Adverse reaction to antidiabetic drug Adverse reaction to antihistamines Adverse reaction to antineoplastic antibiotics Adverse reaction to antiparkinsonism drug Adverse reaction to antiperspirant [icd9data.com]

• Abdominal Pain

  CASE REPORT A 51-year-old Korean man was admitted to our hospital with general weakness and left-side abdominal pain. The patient was diagnosed with acute urate nephropathy with hyperphosphatemia, hyperkalemia, hypocalcemia, and metabolic acidosis. [ncbi.nlm.nih.gov]

  Two weeks after this admission he represented with abdominal pain. A CT showed bilateral renal and bladder calculi without obstruction. [renalfellow.blogspot.com]

  Nine months after her last chemotherapy, she developed right sided abdominal pain. [acanceresearch.com]

  The most common adverse reactions (≥30%) of any grade were febrile neutropenia (69%), constipation (62%), fatigue (62%), thrombocytopenia (54%), abdominal pain (46%), dizziness (46%), hemorrhage (46%), nausea (46%), pneumonia (excluding fungal) (46%), [venclextahcp.com]

  Case presentation A 66-year-old African American male with past history of hypertension, smoking (20 pack years), and diabetes mellitus was admitted to the hospital because of worsening right upper quadrant abdominal pain which started 3 weeks ago (negative [jgo.amegroups.com]

• Heart Disease

  The risk is based on: the type of cancer how far the cancer has progressed pre-existing conditions, such as poor kidney function, heart disease or high blood pressure lab tests If you have a risk of developing TLS, your healthcare team can suggest ways [cancer.ca]

  Patients with uncontrolled ischemic heart disease or congestive heart failure (CHF). 4. Pregnant or breast feeding women. 5. Patients with sUA levels ≥ 10 mg/dL at randomization (Visit 1). 6. [clinicaltrialsregister.eu]

  Some people may also develop carcinoid heart disease, where the heart valves thicken and stop working properly. [nhs.uk]

  The high prevalence of obesity means a higher risk of type 2 diabetes, heart disease, and stroke than in other people. Similarly, people with PWS have a higher rate of tooth erosion than others. [medicalnewstoday.com]

• Muscle Cramp

  muscle cells), and may trigger life-threatening arrhythmias. Signs & Symptoms: Patients may develop muscle cramps, muscle weakness, paresthesias, nausea, vomiting and diarrhea. [learn.pediatrics.ubc.ca]

  This places the patient at risk for cardiac arrhythmias and cardiac arrest, as well as muscle cramps and paresthesias. To prevent hyperkalemia, potassium should be withheld from IV fluids. [healio.com]

  […] hematology | 8 January, 2016 | 1 A young lad with acute lymphocytic leukemia (ALL) shows up to your ED feeling very weak and c/o sever muscle cramps. On further questioning he reveals that he started chemotherapy 3 days ago. [sinaiem.org]

  Symptoms are generally nonspecific and can include: Nausea with or without vomiting Lack of appetite and fatigue Dark urine, reduced urine output, or flank pain Numbness, seizures, or hallucinations Muscle cramps and spasms Heart palpitations Kidney failure [jamanetwork.com]

  cramps, syncopy, heart failure, and cardiac dysthymias. [voice.ons.org]

• Muscle Spasm

  spasms, parasthesiae, bronchospasm, laryngospasm, hypotension Note: Original 2004 Cairo-Bishop criteria do not specify oliguria or symptomatic hypocalcemia within the definition of clinical TLS. 1 Commentary Acronyms References Cairo-Bishop criteria [bloodref.com]

  spasms/tetany Uric acid: Oliguric renal failure diagnosis (back to contents) urinalysis May see uric acid crystals. simplified Cairo definition of tumor lysis syndrome Laboratory definition = Malignancy plus at least two of the following abnormalities [emcrit.org]

• Seizure

  Electrolyte abnormalities should be corrected to avoid arrhythmias and seizures. [the-hospitalist.org]

  None - One brief, generalized seizure; seizure(s) well controlled by anticonvulsants or infrequent focal motor seizures not interfering with activities of daily living Seizure in which there is an altered level of consciousness; poorly controlled seizure [cureus.com]

  Symptom & Signs: Rarely muscles cramps, tetany, seizures, prolonged QT intervals and resulting dysrhythmias may result. [learn.pediatrics.ubc.ca]

  […] malignancies for Tumor Lysis Syndrome include AML, ALL, CML, Burkitt Lymphoma, non- Hodgkins Lymphoma Patients present with metabolic derangements: Hyperkalemia Hyperphosphatemia Hypocalcemia - paresthesias, tetany, + Chvostek and Trousseau, bronchospasm, seizure [emdaily.cooperhealth.org]

  TLS comprises a clinicolaboratory derangement of cellular metabolism which can lead to acute renal impairment, cardiac arrhythmias, seizures and patient demise ( 1 ). [jgo.amegroups.com]

• Renal Insufficiency

  Therefore, caution is necessary when this drug is used in the first-line setting in patients with renal insufficiency or a high tumor burden. [ncbi.nlm.nih.gov]

  Renal insufficiency was defined as a creatinine level of at least 1.5 times the upper limit of normal. He and colleagues then applied these definitions retrospectively to patients treated from 2000 to 2011 in the Henry Ford Health System. [medpagetoday.com]

  Hyperphosphatemia, may be exacerbated by underlying renal insufficiency, uric acid crystal nephropathy, and metabolic acidosis. [learn.pediatrics.ubc.ca]

• Oliguria

  […] criteria, and do not require the criteria to occur within the same 24 hour period. 1 Clinical tumor lysis syndrome One or more of the following, in a patient meeting criteria for laboratory TLS: Creatinine increase of ≥ 26.5 μmol/L (≥ 0.3 mg/dL)*** Oliguria [bloodref.com]

  A 53-year-old man presented with abrupt oliguria. [ncbi.nlm.nih.gov]

  Unfortunately, oliguria and refractory hyperkalemia quickly developed, requiring dialysis. The patient’s condition deteriorated shortly after dialysis, presumably from a large cytokine surge, and he ultimately died. [cmaj.ca]

• Kidney Failure

  Central to its pathogenesis is the rapid accumulation of uric acid derived from the breakdown of nucleic acids, which leads to kidney failure by various mechanisms. [ncbi.nlm.nih.gov]

  Acute kidney failure after chemotherapy. The major cause of acute kidney failure in this setting is hyperphosphatemia, and the main therapeutic means is hemodialysis. [en.wikipedia.org]

• Renal Injury

  A potassium level greater than 7.0 mEq/L is generally considered a hyperkalemic emergency and can be potentiated by ongoing tumor lysis, hypocalcemia, and/or renal impairment.9,10 Acute Renal Injury Acute renal injury is an independent predictor of short-term [archivesofpathology.org]

  Complications Unmanaged and untreated TLS can lead to the following complications: Cardiac dysrhythmias Neuromuscular irritability Severe acute renal injury Acute renal failure Acute uric acid nephropathy Paralysis Tumor lysis syndrome occurs as a result [symptoma.com]

  Further renal injury results from the precipitation of calcium-phosphate in the renal tubules. Lastly, the metabolic acidosis that often develops with renal failure exacerbates the hyperkalemia. [clinicaladvisor.com]

  Associated clinical and laboratory derangements include acute renal injury, cardiac arrhythmias, seizures, and electrolyte abnormalities such as hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia. [gotoper.com]

• Anuria

  The resulting nephropathy may be further exacerbated by pre-existing renal insufficiency (i.e. calcium-phosphate salt crystallization, nephrotoxic medications, etc…) Symptoms: Oliguria, anuria and lethargy Hypercalcemia Causes: Low calcium levels may [learn.pediatrics.ubc.ca]

  Renal replacement therapy  Severe oliguria  Anuria in the absence of hypovolaemia  Significant fluid overload [slideshare.net]

  Given the anuria, he was urgently started on hemodialysis. He was also promptly initiated on vigorous hydration and allopurinol. [academic.oup.com]

  Over the next few hours, asterixis, confusion and anuria with persistent hyperkalemia developed. The patient underwent dialysis without any fluid removal. Two hours after dialysis, profound shock requiring vasopressors developed. [cmaj.ca]

  Among the indications for renal replacement therapy in patients with TLS are: Severe oliguria or anuria Persistent hyperkalemia Hyperphosphatemia-induced symptomatic hypocalcemia A calcium-phosphate product ≥70 mg2/dL2 Author: Pavel Mazánek, MD Tumor [telemedicina.med.muni.cz]

A blood test is done to assess the biochemical profile of the patient. This would include analysis of serum potassium, sodium, bicarbonate and chloride. A urine analysis would also be required in order analyze the urinary output and pH. This is done in order to understand the renal functioning. Monitoring of the urinary output is necessary to observe for signs of oliguric renal failure.

In addition to urine and blood tests, imaging studies such as radiography, CT scan and ultrasonography would also be required. Radiography of the chest is carried out to analyze the presence of large cell tumors. CT scan of the abdomen would also be required if these signs of renal failure are noticed. CT scan of the abdomen would also flourish information regarding the presence of mass lesions in the abdominal region.

Patients are also required to be constantly monitored through electrocardiogram in order to observe any changes in the cardiac functioning.

• Uric Acid Decreased

  The plasma uric acid decrease after rasburicase was significantly larger in patients who did not develop AKI than in those who did (95% vs. 84%; p < 0.01). [ncbi.nlm.nih.gov]

  While uric acid decreased secondary to rasburicase administration, the patient had persistent hyperkalemia, hyperphosphatemia, and a worsening creatinine. Dialysis was attempted but was repeatedly interrupted due to hypotension. [gotoper.com]

  Allopurinol action is rather slow in reducing uric acid concentration, because acts on the new synthesis of uric acid, not on pre-existing uric acid. Hence, several days are necessary for before uric acid levels to decrease. [doi.org]

• Creatinine Increased

  increase of ≥ 26.5 μmol/L (≥ 0.3 mg/dL)*** Oliguria (< 0.5 mL/kg/h for 6 hours) Symptomatic hypocalcemia**** Cardiac dysrhythmia Seizure Sudden death *** or creatinine ≥ 1.5x age-specific upper limit of reference range if no baseline measurement available [bloodref.com]

  TLS is diagnosed as any three or more abnormal serum values: 1) ≥2-fold increase in LDH, 2) ≥50% increase in phosphate, uric acid, or creatinine, 3) ≥30% increase in potassium in the absence of supplementation, and 4) ≥20% decrease in calcium in the absence [jsms.sch.ac.kr]

• Uric Acid Increased

  Rasburicase  Rasburicase is a recombinant urate oxidase that is responsible for the enzymatic conversion of uric acid to allantoin, which is 5–10 times more soluble than uric acid. [slideshare.net]

  Johnson has patents on lowering uric acid as a means to lower blood pressure and improve insulin resistance and a patent application related to lowering uric acid in diabetic renal disease. [journals.plos.org]

• Abnormal Renal Function

  Tumour lysis syndrome is associated with high levels of uric acid, phosphate and potassium along with low levels of calcium and abnormal renal function. [ncbi.nlm.nih.gov]

• Electrocardiogram Change

  Electrolytes imbalances Hyperkalemia: Intravenous calcium gluconate may be given to stabilize cardiac membranes for severe hyperkalemia or for electrocardiogram changes. [clinicaladvisor.com]

Treatment of TLS is geared towards stabilizing the basal parameters and correcting the metabolic disorders [10]. If possible, the cancer treatment should be withheld for some time until the condition of the patient stabilizes.

Treatment should be channelized to correct conditions of acute renal failure. The primary therapy includes use of rasburicase wash to eliminate the excess accumulation of uric acid crystals. In conditions when the patient does not respond to such a treatment method, then dialysis should be administered. A dialysis catheter is required in cases of acute renal failure or in conditions of severe hyperkalemia.

Surgery may often be the treatment of choice for central venous line placement.

The prognosis of the disease condition is unfavorable if timely action is not initiated. The preliminary management of TLS includes effective preservation of renal function, neuromuscular irritability and dysrhythmias. Timely recognition of the signs and symptoms of TLS can help prevent the onset of life threatening complications. Failure to initiate prompt management techniques can lead to multiple organ failure and finally lead to death.

Complications

Unmanaged and untreated TLS can lead to the following complications:

• Cardiac dysrhythmias 
• Neuromuscular irritability
• Severe acute renal injury
• Acute renal failure
• Acute uric acid nephropathy
• Paralysis

Tumor lysis syndrome occurs as a result of aggressive treatment in patients with high grade leukemia who also have elevated counts of white blood cells. It is also a common accompaniment in patients suffering from stage 4 neuroblastoma, hematologic malignancies and hepatoblastoma [6].

Potential candidates for such a syndrome include those patients who have developed tumors that multiply rapidly. In such patients when treatments are employed through radiation therapy, hormonal agents, corticosteroids and monoclonal antibodies, tumor lysis syndrome occurs. The following agents have been known to play a role in the causation of TLS:

• Etoposide
• Bortezomib [7]
• Hydroxyurea
• Paclitaxel
• Thalidomide [8]
• Zoledronic acid 
• Fludarabine

The exact prevalence of TLS varies with different type of malignancies, type of tumor cells and the mode of treatment employed. It has been estimated that in patients with high grade non-Hodgkin lymphomas, tumor lysis syndrome was present in 42% of the cases. Children suffering from acute leukemia and receiving induction chemotherapy, TLS occurred in about 70% of the cases.

Tumor lysis syndrome is a common condition for patients suffering from acute leukemia. However, the current literature suggests that the incidence of TLS is increasing as this syndrome is now known to be associated with those malignant tumors that had rare association with such a condition.

TLS occurs as a result of spontaneous reaction or due to aggressive treatment regimens such as chemotherapy and radiation therapy. The dying tumor cells release several components such as nucleic acids, calcium, phosphate and potassium into the circulation. Release of these components causes the levels to raise giving rise to development of hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. These conditions can in turn cause respiratory distress, cardiac arrhythmias, seizures and kidney failure causing death [9].

Various guidelines have been established for preventing the onset of TLS. These include:

• Patients suffering from leukemia or lymphomas and have a high cell turnover rate should be given allopurinol either orally or through the intravenous route. Allopurinol is a xanthine oxidase which inhibits the production of uric acid and thus acts as a preventive medicine for cancer patients. Patients also need to be given IV fluids to increase urinary output.
• Rasburicase is often used for patients who are at a high risk for developing TLS. It is basically a urate oxidase enzyme that is known to degrade the uric acid.

Tumor lysis syndrome, abbreviated as TLS, refers to a group of disorders that occur as a secondary complication to cancer treatment [1]. In such a kind of syndrome, the dying cells release large quantities of various components such as potassium, nucleic acids and phosphate in the blood circulation. These components are basically byproducts of the dying cells as a result of cancer treatment.

Tumor lysis syndrome is more accentuated in cancers that are rapidly responsive to chemotherapeutic treatment [2]. Release of large quantities of these substances gives rise to various associated conditions such as hyperphosphatemia, hyperkalemia and hyperuricemia that occur due to breakdown of nucleic acids [3]. These conditions in turn cause acute renal failure and acute uric acid nephropathy which are potentially fatal [4]. Tumor lysis syndrome is commonly associated in acute leukemias and high grade non-Hodgkin lymphoma [5].

Definition

TLS occurs in cancer treated patients. In such a condition, the dying tumor cells shed off certain components such as potassium, phosphate and nucleic acids. As a result, the levels of these compounds rise and pave way for development of hyperkalemia, hyperphosphatemia and hyperuricemia.

Cause

Patients with advanced staged cancers often fall prey to such a condition. In this, large tumor cells that multiply at fast rate often shed off the cellular components causing development of secondary complications. Patients who receive aggressive treatment for cancer are also candidates for TLS.

Symptoms

Symptoms of TLS include muscular weakness, tetany, paralysis, emotional labiality, myopathy, papilledema and parkinsonian.

Diagnosis

Blood work is done to reveal the levels of serum potassium, chloride, sodium and bicarbonate. CT scan of the abdomen is also done to analyze the presence of mass lesion in the abdomen. Urine analysis is a necessity to evaluate the urinary output as well as to measure its pH level.

Treatment

Treatment of TLS includes use of rasburicase to eliminate the accumulation of excessive uric acid crystals. This is done to restore back the renal functioning. In severe cases, surgical intervention may be necessary for placement of central venous line or insertion of dialysis catheter.

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2. Jagasia MH, Arrowsmith ER. Complications of hematopoietic neoplasms. In: Wintrobe MM, Greer JP, Foerster J, et al. Wintrobe's Clinical Hematology. Vol II. 11th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2003:1919-44.
3. Arrambide K, Toto RD. Tumor lysis syndrome. Semin Nephrol. May 1993; 13(3):273-80.
4. Kelly KM, Lange B. Oncologic emergencies. Pediatr Clin North Am. Aug 1997; 44(4):809-30.
5. Hande KR, Garrow GC. Acute tumor lysis syndrome in patients with high-grade non-Hodgkin's lymphoma.Am J Med. Feb 1993; 94(2):133-9.
6. Kalemkerian GP, Darwish B, Varterasian ML. Tumor lysis syndrome in small cell carcinoma and other solid tumors. Am J Med. Nov 1997; 103(5):363-7.
7. Jaskiewicz AD, Herrington JD, Wong L. Tumor lysis syndrome after bortezomib therapy for plasma cell leukemia. Pharmacotherapy.Dec 2005; 25(12):1820-5. 
8. Lee CC, Wu YH, Chung SH, et al. Acute tumor lysis syndrome after thalidomide therapy in advanced hepatocellular carcinoma. Oncologist. Jan 2006; 11(1):87-8; author reply 89.
9. Abu-Alfa AK, Younes A. Tumor lysis syndrome and acute kidney injury: evaluation, prevention, and management. Am J Kidney Dis. May 2010; 55(5 Suppl 3):S1-13; quiz S14-9.
10. Jones DP, Mahmoud H, Chesney RW. Tumor lysis syndrome: pathogenesis and management. Pediatr Nephrol. Apr 1995;9(2):206-12