Pediatric Tumor Lysis Syndrome Treatment & Management

  • Author: Alan K Ikeda, MD; Chief Editor: Max J Coppes, MD, PhD, MBA   more...
 
Updated: Jul 30, 2010
 

Medical Care

  • Overview
    • Tumor lysis syndrome (TLS) management requires initiation of preventive measures in high-risk patients prior to cancer treatment, as well as prompt initiation of supportive care for patients who develop acute tumor lysis syndrome during treatment.
    • Patients with evidence of pretreatment acute tumor lysis syndrome should be immediately started on tumor lysis syndrome treatment. Although the correction of all parameters prior to the initiation of chemotherapy is preferable, treatment of the malignancy may be indicated sooner. Identify high-risk patients before treatment by assessing the extent of tumor burden, histopathologic findings, and renal function.
  • Surveillance
    • Severe manifestations of tumor lysis syndrome can be prevented only through meticulous laboratory monitoring and careful clinical observation. Necessary cardiac studies include baseline ECG with follow-up studies or continuous cardiac monitoring during treatment.
    • Appropriate renal surveillance and fluid status determinations require baseline and daily weights, regular vital sign checks, and frequent measurements of both fluid intake and urine output.
    • High-risk patients and those with evidence of tumor lysis syndrome should have laboratory monitoring of BUN, creatinine, uric acid, potassium, calcium, and phosphate levels at least three times a day. Monitoring should continue for the first 48-72 hours after chemotherapy initiation. Some patients may need to be placed on dialysis prior to the initiation of therapy.
  • Control of hyperuricemia
    • Allopurinol is a competitive inhibitor of xanthine oxidase and is given to reduce the conversion of nucleic acid byproducts to uric acid in order to prevent urate nephropathy and subsequent oliguric renal failure.
      • It is usually administered orally at 600 mg/d for prophylaxis and at 600-900 mg/d (maximum of 500 mg/m2/d) for treatment of tumor lysis syndrome.
      • Patients unable to take oral medications can be given intravenous allopurinol. The inhibition of uric acid synthesis promotes an increase of xanthine in both plasma and the renal system.
      • Although reported to be rare, xanthine has the capacity to precipitate in the renal tubules. Other adverse effects include mild-to-severe rash, xanthine stone-induced urolithiasis, acute interstitial nephritis, pneumopathy, fever, and eosinophilia.
      • Dose reduction is necessary in renal insufficiency. Dose reduction is also necessary if concomitantly administered with mercaptopurine, 6-thioguanine, or azathioprine because allopurinol interferes with the metabolism of these agents.
    • Rasburicase (recombinant urate oxidase) is a newer therapy that can be used when the uric acid levels cannot be sufficiently lowered by standard approaches. It has been shown to be both safe and effective in pediatric patients, as well as in adults.
      • Rasburicase has emerged as the preferred choice for treatment of hyperuricemia in tumor lysis syndrome.
      • Rasburicase has a more rapid onset of action than allopurinol. Some urate oxidase is absent in primates; urate oxidase catalyses the conversion of poorly soluble uric acid to soluble allantoin. By converting uric acid to water-soluble metabolites, it effectively decreases plasma and urinary uric acid levels.
      • Unlike allopurinol, uricase does not increase excretion of xanthine and other purine metabolites; therefore, it does not increase tubule crystallization of these compounds.
      • Methemoglobinemia has been reported.[4] Hemolytic anemia and methemoglobinemia may be adverse effects caused by the oxidative stress produced by hydrogen peroxide, which is a by product of the breakdown of urate to allantoin.
  • Hydration
    • Volume depletion is a major risk factor for tumor lysis syndrome and must be vigorously corrected. Aggressive intravenous hydration not only helps correct electrolyte disturbances by diluting extracellular fluid but also increases intravascular volume. Increased volume enhances renal blood flow, glomerular filtration rate, and urine volume to decrease the concentration of solutes in the distal nephron and medullary microcirculation.
    • Ideally, intravenous hydration in high-risk patients should begin 24-48 hours prior to initiation of cancer therapy and continue for 48-72 hours after completion of chemotherapy.
    • Continuous intravenous infusion rates as high as 4-5 L/d (or 3 L/m2/d) yielding urine volumes of at least 3 L/d should be given unless the patient's cardiovascular status indicates impending volume overload.
  • Urinary alkalinization
    • Use of isotonic sodium bicarbonate solutions intravenously to promote alkaline diuresis has the potential benefits of solubilizing, and thus minimizing, intratubular precipitation of uric acid. The goal is to increase urinary pH levels to 7 to maximize uric acid solubility in renal tubules and vessels.
    • Drawbacks to systemic alkaline therapy include magnification of clinical hypocalcemia by shifting ionized calcium to its nonionized form. Increased likelihood of calcium phosphate precipitation in renal tubules is an additional drawback. For these reasons, routine urine alkalinization is controversial and, if used, must include close monitoring of urinary pH, serum bicarbonate, and uric acid levels to both guide therapy and avoid overzealous alkalinization. Consider titrating sodium bicarbonate intravenous fluid solutions to keep the urine pH level at 7-8.
    • If urinary alkalinization is not achieved with exogenous bicarbonate solutions despite increasing serum bicarbonate levels, intravenous acetazolamide at doses of 250-500 mg/d (5 mg/kg/d) may be added to decrease proximal tubule bicarbonate reabsorption, thereby increasing urinary pH level.
  • Control of electrolyte disturbances
    • Aggressively treat and monitor hyperkalemia. Immediately restrict dietary potassium and remove potassium from intravenous fluids. Acute treatment modalities include intravenous infusion of glucose plus insulin to promote redistribution of potassium from the extracellular to intracellular space, and intravenous calcium gluconate as cardioprotection for potassium levels greater than 6.5 mmol/L or for those with ECG alterations. Intravenous hydration with alkaline fluid as described above can also increase intracellular uptake of potassium. Potassium-wasting diuretics may be used with caution because they may worsen renal precipitation in patients with volume contraction. Long-term therapy (eg, oral potassium-exchange resins) should be given immediately because of the transient effectiveness of acute treatment modalities. If these measures fail to control serum potassium, dialysis should be promptly initiated.
    • Hyperphosphatemia is managed with oral phosphate binders and the same solution of glucose plus insulin used for control of hyperkalemia. Hyperphosphatemia may lead to hypocalcemia, which usually resolves as phosphate levels are corrected. In some cases, depressed serum 1,25-dihydroxycholecalciferol levels contribute to hypocalcemia, and administration of calcitriol may correct calcium levels. Such therapy, however, should not be undertaken until serum phosphate levels have normalized to avoid metastatic calcium phosphate calcifications. As a rule, do not correct hypocalcemia unless evidence of neuromuscular irritability is observed, as indicated by a positive Chvostek or Trousseau sign.
    • Use of furosemide or mannitol for osmotic diuresis has not proven to be beneficial as front-line therapy. In fact, these modalities may contribute to uric acid or calcium phosphate precipitation in renal tubules in a volume-contracted patient. Instead, diuretics should be reserved for well-hydrated patients with insufficient diuresis, and furosemide alone should be considered for the normovolemic patient with hyperkalemia or for the patient with evidence of fluid overload.
    • If the previously mentioned methods fail, consider early initiation of dialysis. Dialysis avoids irreversible renal failure and other life-threatening complications. Indications for dialysis include persistent hyperkalemia or hyperphosphatemia despite treatment, volume overload, uremia, symptomatic hypocalcemia, and hyperuricemia.
    • Hemodialysis is preferred over peritoneal dialysis because of better phosphate and uric acid clearance rates. Continuous hemofiltration also has been used and is effective in correcting electrolyte abnormalities and fluid overload.
    • Since hyperkalemia can recur after dialysis is initiated and the high phosphate burden may persist in some patients with tumor lysis syndrome, electrolyte levels must be frequently monitored and dialysis must be repeated as needed.
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Surgical Care

  • Patients with tumor lysis syndrome may need surgical intervention for central venous line placement or the placement of a dialysis catheter in cases of extreme hyperkalemia or renal failure.
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Consultations

  • Patients with cancer who have acute manifestations of tumor lysis syndrome or those at high risk should be treated by personnel who are experienced with tumor lysis syndrome complications and treatment. An oncology unit or ICU with readily available continuous cardiac monitoring and hemodialysis capabilities is preferable.
  • If basic supportive care measures are ineffective in controlling electrolyte disturbances or renal function, nephrology and critical care consultants should be accessible to assist in further management.
  • Laboratory turnover time must be rapid so that metabolic derangements can be addressed before life-threatening problems arise.
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Diet

  • Dietary restrictions highly depend on the status of the individual patient. However, patients who are not restricted to a nothing by mouth diet could theoretically benefit from restricting intake of foods that contain high levels of potassium, phosphorus, or uric acid.
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Contributor Information and Disclosures
Author

Alan K Ikeda, MD  Assistant Professor, Department of Pediatrics, Division of Hematology and Oncology, David Geffen School of Medicine at UCLA; Associate Director of Pediatric Blood and Marrow Transplantation, Mattel Children's Hospital

Alan K Ikeda, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Blood and Marrow Transplantation, and American Society of Pediatric Hematology/Oncology

Disclosure: emedicine Honoraria author

Coauthor(s)

Kathleen M Sakamoto, MD, PhD  Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Co-Associate Program Director of the Signal Transduction Program Area, Jonsson Comprehensive Cancer Center, California Nanosystems Institute and Molecular Biology Institute, University of California, Los Angeles, David Geffen School of Medicine

Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, International Society for Experimental Hematology, Society for Pediatric Research, and Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Koyamangalath Krishnan, MD, FRCP, FACP  Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, James H Quillen College of Medicine at East Tennessee State University

Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians

Disclosure: Nothing to disclose.

Amit P Sarnaik, MD  Staff Physician, Department of Pediatrics, Wayne State University and Children's Hospital of Michigan

Amit P Sarnaik, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Specialty Editor Board

Stephan A Grupp, MD, PhD  Director, Stem Cell Biology Program, Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania School of Medicine

Stephan A Grupp, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Steven K Bergstrom, MD  Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland

Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and International Society for Experimental Hematology

Disclosure: Nothing to disclose.

Helen SL Chan, MBBS, FRCP(C), FAAP  Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada

Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA  Senior Vice President, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University School of Medicine; Clinical Professor of Pediatrics, George Washington University School of Medicine and Health Sciences

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

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