Johns Hopkins Advanced Studies in Nursing n 41

ABSTRACT

Tumor lysis syndrome (TLS) is a group ofmetabolic disturbances that can occur followingthe initiation of cytotoxic therapy. It can result inlife-threatening hemodynamic and renal compli-cations if it is not managed correctly. Despite sev-eral advances in supportive care and monitoring,TLS still poses considerable danger to manypatients with cancer. Most of the severe compli-cations of TLS can be prevented through mea-sures, such as hydration, alkalinization, and useof the uric acid-lowering agents allopurinol andrasburicase. Nursing assessment and manage-ment is essential in preventing and treating TLS.This article provides an overview of the patholo-gy and potential complications of TLS, methods ofidentifying high-risk patients, how to prevent TLS,and how to manage complications, focusing onthe nurse’s role in management and monitoring.(Adv Stud Nurs. 2006;4(3):41-48)

Tumor lysis is a primary goal of cancertreatment, but the rapid release of malig-nant cell contents into the circulationpresents metabolic challenges. Tumorlysis syndrome (TLS) is a pattern of meta-

bolic and electrolyte disturbances that can occur fol-lowing the initiation of cytotoxic therapy, and it canresult in life-threatening hemodynamic and renal com-plications if it is not managed correctly. Despite manyadvances in supportive care and monitoring, TLS stillposes considerable danger to many patients with can-cer. However, new therapeutic options are available tohelp prevent TLS, and most of the more severe com-plications are preventable. Nursing management isvital in helping to prevent and treat TLS.1

PATHOLOGY AND COMPLICATIONS

Lysis of tumor cells can result in a rapid influx oftheir contents into the circulation: phosphorus andpotassium, intracellular anions and cations, and themetabolic products of proteins and nucleic acids.Purine nucleic acids break down into hypoxanthineand xanthine and are converted by xanthine oxidaseinto uric acid (Figure 1), which is poorly soluble.2-4

The challenge of metabolizing these materials is com-pounded because unlike normal cells, in which thenucleus and DNA are perfectly defined, cancer cellsare damaged and release DNA components in larger,erratic amounts; they also contain as much as 4 timesthe phosphorus of normal cells.3 This massive influxcan disrupt the normal homeostatic balance of intra-cellular and extracellular fluids (Figure 2),4 causing themetabolic disturbances that characterize TLS (ie,hyperuricemia, hyperkalemia, and hyperphosphatemia

PROCEEDINGS

TUMOR LYSIS SYNDROME: NURSING MANAGEMENT AND NEW THERAPEUTIC OPTIONS*

—

Rita Secola, RN, MSN, CPON†

*Based on a presentation given by Ms Secola at a sym-posium held in conjunction with the ONS 6th Annual Institutesof Learning in Phoenix, Arizona, on November 12, 2005.

†Clinical Manager, Hematology/Oncology/BoneMarrow Transplantation, Children’s Hospital, Los Angeles,California.

Address correspondence to: Rita Secola, RN, MSN,CPON, Clinical Manager, Hematology/Oncology/BoneMarrow Transplantation, Children’s Hospital, 4650 SunsetBoulevard, Los Angeles, California 90027.E-mail: rsecola@chla.usc.edu.

42 Vol. 4, No. 3 n April 2006

PROCEEDINGS

with secondary hypocalcemia). TLS can occasionallyoccur spontaneously before cancer treatment begins,but it occurs most often within 2 to 3 days of initia-tion of therapy, and it can continue for up to 7 days.3

Tumor lysis syndrome can result in life-threateningcomplications. Hyperkalemia can cause cardiac com-plications, such as ventricular arrhythmias that canlead to multiple organ failure and death, in addition tocentral nervous complications, such as seizures.Hyperphosphatemia and hyperuricemia can lead toprecipitation of calcium phosphate salts in the kidney,which can cause obstructive nephropathy. The buildupof nucleic acids, xanthines, and uric acid can compro-mise renal function, potentially resulting in acute renalfailure.2,3 Patients who develop acute renal failure andrequire dialysis face extended hospital stays and highcosts (Figure 3).5 Early identification of high-riskpatients is essential.3,6

INCIDENCE OF TUMOR LYSIS SYNDROME

The precise incidence of TLS is unknown,7 butincidence varies according to treatment regimen, age,and disease. Some of the newer and more aggressivetherapies, with high doses and more challenging typesof therapy, can rapidly reduce tumors and prolong sur-vival, but they seem to cause TLS more often.3

Complications tend to be more severe in older adultsand in older children.2 Leukemia and lymphoma com-monly proliferate and break down rapidly, leading to ahigher rate of TLS than other types of cancer.3

IDENTIFYING PATIENTS AT RISK

DIAGNOSIS

The nurse first assesses a patient’s risk for TLSbased on diagnosis. Patients who have diseases with ahigh tumor growth fraction or high proliferative rateand who are known to be highly sensitive tochemotherapy, radiation, or any other therapy are atthe highest risk. Therefore, the diseases of most con-cern are acute lymphocytic and acute myelogenousleukemia (specifically, T-cell acute leukemia), particu-larly in patients with an extremely high white bloodcell count (WBC) or tumor burden, and any of thehigh-grade B-cell non-Hodgkin’s lymphomas, such asBurkitt’s lymphoma and lymphoblastic lymphoma.Diseases with lesser but demonstrated risk includesome of the intermediate- and low-grade B-cell non-

Hodgkin’s lymphomas, such as large-cell and chroniclymphocytic leukemia; multiple myeloma; some solidand germ cell tumors; small-cell lung carcinoma; breastcarcinoma; medulloblastoma; and neuroblastoma.2,3

DISEASE BULK

A demonstrated large tumor burden is a risk factorfor TLS.3 Children or adults who present with a largeabdominal mass, commonly seen in lymphoma, andpatients with a mediastinal mass are at high risk.

Figure 1. Nucleic Acid Metabolism

Uric Acid Metabolism

Tumor CellLysis

Nucleic Acids

Uric Acid

Urine

HypoxanthineXanthine

Xanthine Oxidase

Adapted with permission from Landier.4

Figure 2. Intracellular Versus Extracellular Fluids

50%

40%

30%

20%

10%

0%

Potassium Phosphate Protein Sodium Chloride Bicarb Other

Cell Plasma

Adapted with permission from Landier.4

Johns Hopkins Advanced Studies in Nursing n 43

PROCEEDINGS

Lymphadenopathy and hepatosplenomegaly canalso be risk factors indicating malignant disease infil-tration into the lymph tissues, liver, and spleen. Theliver and spleen could be swollen because they areassisting in hematopoiesis, or because they are actuallyinfiltrated with leukemia or lymphoma cells.

It is essential to monitor the lactate dehydrogenase(LDH) level.1,6 Laboratory values can vary, but an ele-vated level of LDH that is indicative of a high tumorburden, rapid malignant proliferation, or both clearlyputs a patient at high risk.

RENAL FUNCTION

Renal insufficiency also puts a patient at risk forTLS.2 Children do not often have renal insufficiencybecause they are usually without comorbidities, butadults could have a history of renal issues. In both chil-dren and adults, changes in renal function could sim-ply be because of days of illness and dehydration.

TIME FRAME

Patients are at greatest risk for severe TLS in thefirst 2 to 3 days of hydration and therapy, and theyremain at risk for up to 7 days.3

CAIRO-BISHOP RISK GRADING

Cairo and Bishop present a TLS risk grading sys-

tem to determine the need forassertive prevention and care.3

The first part of the system isbased on laboratory uric acid,potassium, phosphorus, and cal-cium levels. When 2 or more ofthese values are abnormal 3 daysbefore or 7 days after initiationof chemotherapy, more cautionand earlier intervention may bewarranted (Table 1). The secondpart of the grading system isbased on clinical status, clinicalTLS being defined as laboratoryTLS plus 1 or more of the fol-lowing criteria: elevated creati-nine (≥1.5 2 the upper limit ofnormal, adjusted by age), cardiacarrhythmia/sudden death, andseizure, based on potassium andcalcium and not attributable to atherapeutic agent. The risk

grades of 0 to V incorporate laboratory and clinicalTLS (Table 2).3

Figure 3. Length of Stay and Costs for Patients with Leukemia and Lymphomawith Acute Renal Failure

ARF + Dialysisn = 879

ARF + Dialysisn = 1045

ARF w/out Dialysisn = 5185

No ARF or Dialysis

n = 172 275

Dialysis

n = 172 275

0

10

20

Day

s

ARF w/out Dialysis n = 4588

No ARF or Dialysis n = 157 427

30

*P <.01

0

10 000

50 000

100 000

ARF + Dialysis n = 879

ARF w/out Dialysis n = 4588

Dialysis

n = 157 427

ARF + Dialysis n = 1045

ARF w/out Dialysis n = 5185

P <.01

*

**

Length of Stay (LOS)*

US

Dol

lars

*

*

*

**

CostsLeukemia Lymphoma

No ARF or

No ARF or

ARF = acute renal failure.Data from Bell et al.5

Table 1. Cairo-Bishop Definition of LaboratoryTumor Lysis Syndrome

Two or more of the following within 3 days before or 7 daysafter chemotherapy initiation:

Uric acid x ≥8 mg/dL (476 µmol/L)* or25% increase from baseline

Potassium x ≥6.0 mEq/L (6.0 mmol/L) or25% increase from baseline

Phosphorus x ≥6.5 mg/dL (2.1 mmol/L; children),x ≥6.5 mg/dL (2.1 mmol/L; adults?), or25% increase from baseline

Calcium x ≤7.0 mg/dL (1.75 mmol/L) or25% decrease from baseline

Assessment assumes hydration (± alkalinization) and uric acid-loweringagent will be started.*8 is the high normal, but it can be a little higher without cause for alarmin adults; in children, this number is used strictly.Reprinted with permission from Cairo, Bishop. Br J Haematol.2004;127:3-11.3

44 Vol. 4, No. 3 n April 2006

PATIENT ASSESSMENT

OBTAINING AND ASSESSING LABORATORY VALUES

After assessing the patient’s risk factors, the nurseobtains laboratory values. Most important are therenal values, LDH, and WBC. Serum calcium-phos-phorus solubility product factor (serum calcium 2serum phosphorus) is also important. Calcium willbind with excess phosphorus, resulting in hypocal-cemia, and if the calcium-phosphorus level reaches 60or higher, calcium phosphate salts precipitate, whichcan lead to obstructive nephropathy.2,6

RADIOLOGY

Radiologic procedures to assess TLS risk typicallyinclude a chest X ray and renal ultrasound. Use ofintravenous (IV) contrast material should be avoidedin these procedures because of the additionalstress it places on the kidneys to excrete the“heavy” contrast substance. Chest and abdomi-nal computed tomography scans are also fre-quently used to assess tumor size and location, inaddition to assessing risk for TLS.

Special attention should be paid to theabdomen in radiologic scans. Sometimes renaldysfunction is caused not by hyperuricemia but bythe lymphoma pressing on the renal blood flow orthe kidneys, which may require interventionbefore the patient begins therapy. Looking formediastinal masses is also important.6

OBTAINING THE PATIENT HISTORY

Obtaining the patient history is another areawhere the nurse plays an essential role in being alertfor signs of TLS. Signs of obstructive nephropathyinclude flank pain, hematuria, and decreased urineoutput. Lethargy, nausea and vomiting, edema,and oliguria can indicate hyperuricemia.Hypocalcemia signs include muscle cramps,twitching, numbness, tingling, carpopedal spasms,and seizures.3 The most potentially life-threateningabnormality is hyperkalemia, and some of itssymptoms, such as nausea, diarrhea, cramping, andweakness, can be a result of the patient’s disease orshort-term illness rather than TLS. The nurse mustdetermine whether the patient is having more spe-cific symptoms, such as irregular heartbeat, ven-tricular arrhythmias, QRS widening, heart block,or especially elevated T waves.3

Obtaining a history can be difficult in children, butthe child and family may be able to provide much ofthe necessary information, such as how often the childis going to the bathroom. Edema is one of the symp-toms more obvious to children—little boys noticetheir testes may be swollen, and older children maynotice other signs of swelling. A decline in the use oftrue fine motor skills can indicate spasms in children.

The nurse then completes the physical assessment:checking vital signs, respiratory function, blood pres-sure, and cardiac function, and examining the patientfor lymphadenopathy, abdominal masses, ascites,edema, and weight changes.

PREVENTION OF TUMOR LYSIS SYNDROME

The foundation of managing TLS is prevention,

PROCEEDINGS

Table 2. Cairo-Bishop Grading System for Tumor Lysis Syndrome

Grade LTLS Creatinine Cardiac Arrhythmia Seizure

0 — ≤1.5 2 ULN None None

I + 1.5 2 ULN Intervention not Noneindicated

II + >1.5–3.0 Nonurgent medical One brief generalized2 ULN intervention indicated seizure; seizure(s)

well controlled orinfrequent; focal motor seizures not interfering with ADL

III + >3.0–6.0 Symptomatic and Seizure in which2 ULN incompletely consciousness is

controlled altered; poorlymedically or controlled seizurecontrolled with disorder;device breakthrough

generalized seizures,despite medicalintervention

IV + >6.0 2 ULN Life-threatening Seizures of any kindthat are prolonged,repetitive, or difficultto control

V + Death* Death* Death*

*Probably or definitely attributable to clinical tumor lysis syndrome.ADL = activities of daily living; LTLS = laboratory tumor lysis syndrome; ULN = upper limitof normal.Reprinted with permission from Cairo, Bishop. Br J Haematol. 2004;127:3-11.3

Johns Hopkins Advanced Studies in Nursing n 45

before and during cytotoxic therapy. Metabolic stabil-ity should be established before initiating treatment, ifthe nature of the disease allows for a delay.3

HYDRATION

Hydration is the first and most important line ofprevention. IV fluid should be 3000 mL/m2/24hours or more (amount may vary depending on ageand comorbidities) and continued for several days tomaintain a urine output of more than 100cc/m2/hour and a urine specific gravity of less than1.010.2,6 It is especially important to work withphysicians and residents to ensure that the patientreceives no additional potassium during hydration,even if the patient’s potassium level is normal,2,3

because the patient will be exposed to an elevatedlevel of potassium when lysis begins.

ALKALINIZATION

Alkalinization is a common but more controversialpreventative measure. When used, urine pH shouldnot exceed 7.0.8 Decreasing the acidity of the renalenvironment makes it less conducive to hosting xan-thines and uric acid. Sodium bicarbonate can beadministered orally, in the patient’s IV maintenance,or as intermittent boluses, according to physician orinstitution preference. Serum bicarbonate should beless than 30 mEq/L and discontinued when uric acidis normal or serum phosphorus is elevated, and urinepH should be maintained between 7.0 and 7.5. If theurine becomes too alkaline, calcium and phosphatecan precipitate in the kidney.2,6

ALLOPURINOL

Allopurinol has long been used to help preventTLS. It blocks uric acid production by inhibiting xan-thine oxidase, and it is effective in preventing furtherdevelopment or buildup of uric acid (Figure 4).3,4

Allopurinol is predominantly administered orally.It is also available in an IV formulation. For youngchildren, the tablets must be crushed up and adminis-tered 3 times a day, but it is easily given.

Because allopurinol does not typically produce animmediate response, it may not provide enough renalprotection for high-risk patients.6 It also does notaffect the uric acid that has already formed, which is aconcern in patients with an elevated level of uric acid.3

Allopurinol administration can also result in hypoxan-thine and xanthine accumulation.1,3

RASBURICASE

Rasburicase is a newer uric acid-lowering agent,and it is currently the only pharmacologic alternativeto allopurinol. It is a recombinant urate-oxidaseenzyme derived from the Aspergillus flavus gene, and itworks by oxidizing uric acid into the water-solublesubstance allantoin, which the kidney excretes easily(Figure 5).4

PROCEEDINGS

Figure 4. Allopurinol Mechanism of Action

Allopurinol: Blocks Uric Acid Production

Tumor CellLysis

Uric Acid

Urine

HypoxanthineXanthine

Xanthine Oxidase ALLOPURINOL

Nucleic Acids

Adapted with permission from Landier.4

Figure 5. Rasburicase Mechanism of Action

Rasburicase: Converts Uric Acid to Allantoin and Promotes Excretion

Uric Acid

Urine

HypoxanthineXanthine

Xanthine Oxidase RASBURICASE

Nucleic Acids

Tumor CellLysis

Allantoin

Adapted with permission from Landier.4

46 Vol. 4, No. 3 n April 2006

PROCEEDINGS

Rasburicase has been used for a few decades inEurope and was approved by the US Food and DrugAdministration in 2002 for pediatric use. It is availableonly as an IV drug, and it is administered once a dayas a 15- to 30-minute infusion. It is approved for usefor 5 days but, in practice, does not often require morethan 1 to 3 doses, an advantage clinically and finan-cially.3 It has been shown to be effective in decreasinguric acid level, and it also prevents xanthine buildupbecause it works at the end of the uric acid metabolicpathway.1,9 Because it induces a rapid response,1

patients do not need to be alkalinized, and it can helpprevent the delay of chemotherapy.1

In its current recombinant form, rasburicase doesnot commonly cause significant allergic reactions, sen-sitivities, or the development of neutralizing antibod-ies, as does the more “pure” form used in Europe.9

However, some studies have reported that antibodiesto rasburicase developed in small numbers ofpatients,10,11 thus caution is recommended whenretreatment is considered.8 Incidence of antibodiesmay be detected 1 to 6 weeks after infusion.

Nurses administering rasburicase should be awarethat its rapid action can degrade uric acid in bloodsamples at room temperature, resulting in an artificial-ly low level of uric acid. Therefore, when obtainingtumor lysis laboratory values, blood samples should becollected in prechilled heparin tubes, immediatelyplaced in ice, and should be analyzed within 4 hoursof collection.1

RASBURICASE VERSUS ALLOPURINOL

Comparative clinical dataGoldman et al performed a randomized, multicen-

ter trial comparing allopurinol and rasburicase in 52patients aged 4 months to 17 years with leukemia orlymphoma who were at high risk for TLS.12 Patientsreceived allopurinol 10 mg/kg orally every 8 hours orrasburicase 0.2 mg/kg IV daily for 5 to 7 days. The pri-mary endpoint was control of uric acid level duringthe first 96 hours of therapy, as determined by areaunder the curve. Baseline uric acid levels were 6.8 ±3.4 mg/dL and 7.7 ± 3.5 mg/dL in patients receivingallopurinol and rasburicase, respectively.12

The investigators found that patients receiving ras-buricase experienced a rapid and dramatic response—4hours after the first dose, patients achieved an 86% reduc-tion in uric acid versus a 12% reduction with allopurinol(P <.0001). The median time to achieve a uric acid level

of less than 8 mg/dL following first dose in patientsreceiving rasburicase and allopurinol was 4 hours and 23hours, respectively. One patient receiving allopurinoldeveloped renal failure requiring assisted renal supportversus none of the patients receiving rasburicase. Nopatients developed antibodies to rasburicase.12

Adverse reactions/contraindicationsNeither allopurinol nor rasburicase commonly caus-

es problems in children or adults.9 The most commonadverse reaction to allopurinol is a rash, and patients whohave had any type of allergic response to it in the past,such as severe rash or liver toxicity, should not repeat thedrug.1,12 The most common adverse reactions to rasburi-case are fever, nausea, vomiting, and headache. Allergicreactions to rasburicase can include anaphylaxis, rash,hemolysis, and methemoglobinemia. Patients should bemonitored for allergy and hypersensitivity because theimmunogenicity of rasburicase varies by patient.

Patients with glucose 6-phosphate dehydrogenasedeficiency should not receive rasburicase. Nurses shouldscreen patients of African-American or Mediterraneanancestry for this deficiency and ask about family history.1

CostOral allopurinol is less expensive than rasburicase

but, at a cost of $485.95 for a 500-mg vial, the IVpreparation of allopurinol is more expensive thanallopurinol tablets ($0.05–$0.11 per 100-mg tablet).13

Rasburicase is $386.78 per 1.5-mg vial and, as men-tioned, treatment may require 1 to 5 doses.3,13 Clinicalconsiderations should outweigh cost if a patient can beprevented from going to the intensive care unit (ICU),undergoing dialysis, or undergoing hemofiltration.

CAIRO-BISHOP RECOMMENDATIONS

Cairo and Bishop present recommendations for theuse of allopurinol and rasburicase (Table 3).3 The investi-gators suggest that rasburicase be used for patients athigher risk for TLS, who would probably benefit morefrom the faster-acting drug. A WBC of approximately 50000 is one of the guidelines they use to determine who isat greatest risk. Other factors include disease type, renalstatus, and the aggressiveness of the planned treatment.3

Some centers use a WBC of closer to 100 000 as aguideline. Some pharmacies may not have rasburicaseon formulary. There will need to be more educationand implementation processes instituted over the nextfew years.

Johns Hopkins Advanced Studies in Nursing n 47

PROCEEDINGS

MONITORING AND ASSESSMENT

Ongoing thorough monitoring and assessment areessential, including ensuring hydration and checkingvital signs at least every 4 hours. Tumor lysis laborato-ry values should be obtained every 6 to 12 hours min-imum, especially during the first few days oftreatment. The nurse also should continuously moni-tor cardiac, respiratory, neuromuscular, and gastroin-testinal function, in addition to checking for edemaand weight changes.6

Cardiac monitoring can be challenging because notall centers have the ability to monitor hematology/oncology patients outside of the ICU. Sometimespatients will need to be moved to the ICU to assureproper monitoring. In the ICU, more intensive nurs-ing is provided until the patient is deemed metaboli-cally and hemodynamically stable. Patients who showsigns of hyperkalemia must be monitored; interven-tion will be required if the patient has an abnormalheart rate or rhythm or a potassium level of 6.5 mEq/Lor more or calcium level of 7.0 mg/dL or less.6

MANAGEMENT OF TUMOR LYSIS

SYNDROME COMPLICATIONS

Patients with hyperkalemia should receive IVfurosemide or another appropriate diuretic. Oral sodi-um polystyrene sulfonate is an option, but it is notindicated if potassium is rising quickly. A glucose andinsulin infusion can be helpful, in addition to IV sodi-

um bicarbonate, pushing the extra potassium andphosphorus back into the cell. IV calcium gluconate iseffective and also helps prevent hypocalcemia, but it isnot a first choice because of the potential of develop-ing calcium salts in the kidneys. Dialysis may be nec-essary in severe cases.2,3

For patients with hyperuricemia, treatment beginswith vigorous hydration.2 Alkalinization with allopuri-nol is appropriate for most patients, and rasburicase isrecommended for higher-risk patients.3 Forcing diure-sis with furosemide or mannitol is another option. Ifthe patient develops acute renal failure that does notrespond to more conservative management, hemofil-tration or dialysis may be necessary.2,3

To treat hyperphosphatemia, an oral phosphatebinder, such as aluminum hydroxide, is recommend-ed; phosphates in diet and medication should also berestricted. Additionally, a glucose and insulin infusioncan be effective.2,3

Table 3. Recommendations for Uric Acid-LoweringTherapy

Allopurinol Rasburicase

Uric acid level Normal Elevated

Tumor type Nonhematologic; Burkitt’s lymphoma,Hodgkin’s lymphoma, lymphoblasticCML lymphoma, ALL, AML

Tumor burdenWBC count ≤50 2 109/L >50 2 109/LLDH ≤2 2 normal >2 2 normal

Cytoreductive intensity Mild Aggressive

Kidney tumor infiltration Absent Present

ALL = acute lymphocytic leukemia; AML = acute myelogenous leukemia; CML =chronic myeloid leukemia; LDH = lactate dehydrogenase; WBC = white blood cell.Reprinted with permission from Cairo, Bishop. Br J Haematol. 2004;127:3-11.3

CASE STUDY

AN OLDER CAUCASIAN BOY WITH A HIGH LEUKOCYTE COUNT,

SUBSTANTIAL LYMPHADENOPATHY,AND SPLENOMEGALY

—

When Alex, a 10-year-old Caucasian boy, initiallyappeared for evaluation, he had a high leukocytecount (79 K/µL), substantial lymphadenopathy, anenlarged spleen, and a large mediastinal mass, whichare all risk factors for tumor lysis syndrome (TLS). Inaddition, his age bordered the age at which risk ofTLS becomes elevated in children.

Results of laboratory analysis revealed a potassiumlevel of 4.1 mEq/L, and a phosphorus level of 4mg/dL. The uric acid level was 16.1 mg/dL, which isextremely and atypically high for pediatric patients.The calcium level was 9.6 mg/dL, the blood ureanitrogen level (BUN) was 12 mg/dL, and the creati-nine level was 1 mg/dL, which was not ideal but notthat severely elevated. The lactate dehydrogenase(LDH) level was 6323 U/L, which prompted tremen-dous concern because an LDH level of 300 to 500U/L is within normal limits.

(continued on page 48)

48 Vol. 4, No. 3 n April 2006

PROCEEDINGS

Hypocalcemia should be managed by first treatinghyperphosphatemia. If the hypocalcemia does notresolve and the patient is experiencing seizures or car-diac symptoms, seizure precautions and IV calciumgluconate are warranted.2,3

CONCLUSIONS

Nurses play a pivotal role in the prevention and earlyrecognition of TLS by identifying high-risk patients;using measures, such as hydration, alkalinization, anduric acid-lowering therapy; and vigilant monitoring.With advances in risk assessment, monitoring, and sup-portive care, in addition to the new option of rasburi-case, fewer patients may now develop TLS.

REFERENCES

1. Brant JM. Rasburicase: an innovative new treatment forhyperuricemia associated with tumor lysis syndrome. Clin JOncol Nurs. 2002;6:12-16.

2. Rheingold SR, Lange BJ. Oncologic emergencies. In: PizzoPA, Poplack DG, eds. Principles and Practice of PediatricOncology. 4th ed. Philadelphia, Pa: Lippincott;2002:1177-1203.

3. Cairo MS, Bishop M. Tumor lysis syndrome: new therapeuticstrategies and classification. Br J Haematol. 2004; 127:3-11.

4. Landier W. Tumor lysis syndrome. Presented at: SouthernCalifornia Association of Pediatric Oncology Nurses AnnualMeeting; May 3, 2002; San Diego, Calif.

5. Bell T, Candrilli S, Irish W, et al. Medical resource use andcosts associated with renal complications among patients withhematologic malignancies [abstract]. Blood. 2002;100:221a.

6. Secola R, Bergeron S, Cairo MS, Bessemetry O. Children’sOncology Group Nursing Clinical Practice Committee: TLSNursing Guidelines; 2004.

7. Truini-Pittman L, Rossetto C. Pediatric considerations in tumorlysis syndrome. Semin Oncol Nurs. 2002;18:17-22.

8. Fernandez PC, Larson RA, Agus ZS. Tumor lysis syndrome. UpTo Date, 2006, Online 13.3. Available at: www.utdol.com.Accessed January 16, 2006.

9. Pui CH, Jeha S, Irwin D, Camitta B. Recombinant urate oxi-dase (rasburicase) in the prevention and treatment of malig-nancy-associated hyperuricemia in pediatric and adultpatients: results of a compassionate-use trial. Leukemia.2001;15:1505-1509.

10. Pui CH, Mahmoud HH, Wiley JM, et al. Recombinant urateoxidase for the prophylaxis or treatment of hyperuricemia inpatients with leukemia or lymphoma. J Clin Oncol.2001;19:697-704.

11. Lascombes F, Sommelet D, Gebhard F, et al. High efficacyof recombinant urate oxidase in prevention of renal failurerelated to tumour lysis syndrome (TLS) [abstract]. Blood.1998;92(suppl 1):237b.

12. Goldman SC, Holcenberg JS, Finklestein JZ, et al. A ran-domized comparison between rasburicase and allopurinolin children with lymphoma or leukemia at high risk for tumorlysis. Blood. 2001;97:2998-3003.

13. 2005 Redbook: Pharmacy’s Fundamental Reference.Montvale, NJ: Thomson Healthcare; 2005;336:209-210.

(continued from page 47)

In response, the second-year resident who evaluatedAlex ordered hydration. She also ordered supplementalpotassium chloride (20 mEq/L), administered in 3000mL of intravenous fluid per square meter every 24hours, which was inappropriate but was corrected. Abone-marrow specimen obtained by aspirated biopsytested positive for T-cell leukemia, which is another riskfactor for TLS. Initiation of chemotherapy was orderedas soon as metabolic stability could be achieved.

After alkalinization, hydration, and allopurinolwere administered, Alex’s urine was found to have apH of 8 and a specific gravity of 1.017. Additionalhydration was required. After additional hydration, atypical 4-drug induction chemotherapy regimen con-sisting of daunorubicin, vincristine, prednisone, andL-asparaginase was initiated. Eight hours later, uri-nary output decreased such that Alex was only pro-ducing 120 mL of urine in 4 hours, and the leukocytecount was 31.8 K/µL, which indicated that Alex hadexperienced massive tumor lysis in the past 8 hours.Laboratory results included a potassium level of 5.4mEq/L, which had crept up since the previous test,and a phosphorus level of 14.5 mg/dL, which hadmore than tripled since the previous test. Other find-ings included a uric acid level of 11 mg/dL, which wasstill elevated; a low calcium level of 5.1 mg/dL, whichhad decreased; a creatinine level of 1.7 mg/dL, whichhad increased; and a BUN level of 38 mg/dL, whichhad more than tripled since the previous test.

Because the most recent uric acid and potassiumlevels prompted extreme concern in the nursing staff,Alex received glucose therapy, insulin therapy, andintensive monitoring in the intensive care unit (ICU)for the first few days after initiation of chemotherapy.However, although he remained in the ICU for a fewdays, Alex never required hemofiltration or dialysis.Within 4 days of ICU admission, results of laborato-ry testing became normal, and leukocyte count haddecreased to 1.2 K/µL, which prompted his transferto the hematology/oncology unit. Although Alexeventually had a good outcome, he would have beendeemed a high-risk patient for TLS and would havebenefited from initiation of rasburicase therapy beforeinitiation of chemotherapy.