38

Tumor Lysis Syndrome

Scott C. Howard

SUMMARY

O F

K E Y

P O I N T S

Tumor lysis syndrome can occur in

any patient with newly diagnosed
or relapsed cancer, and thus all
patients should undergo risk
stratification and management
according to their risk for clinical
tumor lysis syndrome.
Laboratory tumor lysis syndrome is
defined as the presence of two or
more of the following abnormalities
present on the same day:
hyperuricemia, hyperkalemia,
hyperphosphatemia, and
hypocalcemia as a result of
hyperphosphatemia.
Clinical tumor lysis syndrome is
defined as laboratory tumor lysis
syndrome plus acute kidney injury,
symptomatic hyperkalemia, or
symptomatic hypocalcemia, and it

should be prevented whenever

possible.
The incidence of clinical tumor lysis
syndrome depends on the number of
risk factors present at presentation
and on the management of patients
potentially at risk.
Risk factors for clinical tumor lysis
syndrome include a large cancer
mass, high cell lysis potential
(chemosensitivity), and patient
factors (e.g., preexisting
nephropathy, dehydration, acidosis,
hypotension, and nephrotoxin
exposure).
Management depends on the risk of
the development of clinical tumor
lysis syndrome:
Negligible riskno prophylaxis, no
monitoring

EPIDEMIOLOGY AND DEFINITION

Tumor lysis syndrome is a potentially fatal metabolic condition that
occurs in patients with rapidly proliferating, bulky, or chemosensitive
tumors (Table 38-1).1 It has been most commonly reported in
patients with high-grade non-Hodgkin lymphomas (NHL) and acute
leukemias, but it can occur in persons with virtually any type of
cancer when a large cancer cell mass is present and the cancer is sensitive to initial therapy.

ETIOLOGY AND PATHOGENESIS

Tumor lysis syndrome occurs most commonly after treatment with
cytotoxic therapy, but it can also occur spontaneously in patients with
highly proliferative tumors. By releasing tumor cellular components
into the bloodstream, tumor lysis syndrome results in metabolic
abnormalities including hyperphosphatemia, hyperkalemia, hypocalcemia, hyperuricemia, and azotemia (Fig. 38-1). Acute kidney injury,
seizures, cardiac arrhythmias, nausea, and vomiting may occur as a
result of these metabolic abnormalities. To reduce morbidity and
mortality, early diagnosis and identification of patients at risk for
tumor lysis syndrome are of the utmost importance.1,2 The catabolism
of nucleic acids ultimately results in the production of uric acid.3
Purines are first degraded into hypoxanthine, then xanthine, and
finally into uric acid through the action of xanthine oxidase.4,5 Hyperuricemia leads to the deposition of uric acid crystals in the renal

Low risk (1% risk for clinical tumor

lysis syndrome)hyperhydration,
allopurinol, and daily laboratory
evaluation
Intermediate riskhyperhydration,
rasburicase, inpatient monitoring,
and laboratory evaluation every 8
to 12 hours
High riskhyperhydration,
rasburicase, cardiac monitoring on
the inpatient ward, laboratory
evaluation every 6 to 8 hours, and
rapid access to hemodialysis
Established clinical tumor lysis
syndrome at presentation
hyperhydration, rasburicase,
cardiac monitoring in the intensive
care unit, laboratory evaluation
every 4 to 6 hours, and rapid
access to hemodialysis

tubules because of the poor solubility of uric acid and can result
in acute kidney injury.4 Hyperphosphatemia can also cause acute
kidney injury. Phosphates combine with calcium, generating
calcium phosphate salts that deposit in the renal tubules. The binding
of calcium by phosphate leads to hypocalcemia, which in turn can
cause vomiting, muscle cramps, tetany, paresthesias, seizures, and
cardiac dysrhythmias.6 Hyperkalemia from cellular lysis can lead to
cardiac dysrhythmias, ventricular tachycardia, fibrillations, or cardiac
arrest.6

RISK FACTORS AND INCIDENCE OF TUMOR

LYSIS SYNDROME
Several risk factors for tumor lysis syndrome have been identified,
including tumor-related factors, individual patient characteristics,
and the type of chemotherapy used.7 Certain tumor types have historically been associated with an increased risk for the development
of tumor lysis syndrome, including Burkitt leukemia, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (especially those with
inv(16) chromosomal translocation), and NHL (particularly Burkitt
lymphoma)8-10; patients with these tumor types were the most
frequently enrolled in compassionate-use trials of hypouricemic
agents.11,12 However, tumor lysis syndrome can also develop in
patients with chronic lymphocytic leukemia (CLL) and chronic
myelogenous leukemia.13 Acute leukemias and high-grade lymphomas often have a high proliferative rate, a large tumor burden, and

591

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Part II: Problems Common to Cancer and Its Therapy

Table 38-1 Modified Cairo-Bishop Classification of Tumor Lysis Syndrome
Laboratory tumor lysis
syndrome

Two or more of the metabolic abnormalities in

the next column present on the same day
Occurring within 3 days before initiation of
therapy or 7 days after initiation of therapy
Assumes the patient receives adequate
hydration and a hypouricemic agent

Uric acid 476 mol/L (8mg/dL) in adults or the upper

limits of normal in children
Potassium 6.0mmol/L
Phosphorus 1.5mmol/L (4.5mg/dL) in adults or
2.1mmol/L (6.5mg/dL) in children
Calcium 1.75mmol/L (7mg/dL) or ionized calcium
<0.3mmol/L (1.12mg/dL)

Clinical tumor lysis

syndrome

Laboratory tumor lysis syndrome plus any of

the criteria in the next column (not
attributable to other causes)

Acute kidney injury, defined as an increase in creatinine of

26.5 micromoles/L (0.3mg/dL) or when no baseline
creatinine is documented, a single value 1.5 times the
upper limits of normal for the patients age and sex
Symptomatic hypocalcemia (e.g., tetany or paresthesias),
seizure, cardiac dysrhythmia, or sudden death attributed
to hypocalcemia or hyperkalemia

Data from reference 1.

Lysis of cancer cells with release of intracellular contents

DNA

Phosphate

Potassium

Cytokines

DNAase breaks down

DNA, releasing purines

Adenosine

Guanosine

Inosine

Guanine

Hypotension

Inflammation

Acute
kidney injury

Hypoxanthine
Xanthine oxidase

Allopurinol

Xanthine
Xanthine oxidase

Allantoin

No tumor lysis
syndrome

Rasburicase

Uric acid

Phosphate

Urinary excretion

Potassium

Accumulation

Tumor lysis
syndrome

Figure 38-1 Pathophysiology of tumor lysis syndrome. Lysis of cancer cells releases DNA, phosphate, potassium, and cytokines. DNA released from

the lysed cells is metabolized into adenosine and guanosine, both of which are converted into xanthine. Xanthine is then oxidized by xanthine oxidase, leading
to the production of uric acid, which is excreted by the kidneys. When the accumulation of phosphate, potassium, xanthine, or uric acid is more rapid than
excretion, tumor lysis syndrome develops. Cytokines cause hypotension, inflammation, and acute kidney injury, which increase the risk for tumor lysis syndrome. The bidirectional dashed line between acute kidney injury and tumor lysis syndrome indicates that acute kidney injury increases the risk of tumor
lysis syndrome by reducing the ability of the kidneys to excrete uric acid, xanthine, phosphate, and potassium. By the same token, development of tumor lysis
syndrome can cause acute kidney injury by renal precipitation of uric acid, xanthine, and calcium phosphate crystals and by crystal independent mechanisms.
Allopurinol inhibits xanthine oxidase and prevents the conversion of hypoxanthine and xanthine into uric acid but does not remove existing uric acid. In
contrast, rasburicase removes uric acid by enzymatically degrading it into allantoin, a highly soluble product that has no known adverse effects on health.

are particularly sensitive to chemotherapy; the combination of high

tumor bulk and sensitivity to therapy make tumor lysis syndrome
more likely.14 The high nucleic acid, phosphorus content, and
increased activity of purine metabolism in these tumors predispose
patients to tumor lysis syndrome.7 In a study of 102 patients with
high-grade NHL who received prophylactic hyperhydration and allopurinol, the incidence of clinically significant tumor lysis syndrome
was 6%, and one patient required dialysis.15 A retrospective study of

755 patients with NHL or acute leukemia who received rasburicase

for prevention or treatment of tumor lysis syndrome documented a
5.3% incidence of tumor lysis syndrome (including both laboratory
and clinical tumor lysis syndrome).16 Seven patients in this study died
from tumor lysis syndrome (0.9% of all patients and 17.5% of
patients with tumor lysis syndrome).16,17 In a multinational study of
235 pediatric patients with advanced-stage, B-cell NHL who were
treated with the same chemotherapy regimen, 27% and 15% of U.S.

Tumor Lysis Syndrome CHAPTER 38 593

patients (who all received allopurinol) experienced tumor lysis syndrome and required dialysis, respectively, whereas 11% and 3% of
French patients (who all received rasburicase) experienced tumor lysis
syndrome and required dialysis, respectively.18 Hence the risk for
tumor lysis syndrome depends not only on tumor-related risk factors
but also on the supportive care used (Fig. 38-1).
In addition to tumor-related risk factors for tumor lysis syndrome,
patient-related factors affect tumor lysis syndrome risk, including
leukocytosis, hyperuricemia, elevated serum lactate dehydrogenase,
elevated serum creatinine, renal insufficiency, dehydration, acidic
urine, and decreased urinary flow at the time of presentation.7,14
Finally, specific cytotoxic agents have been associated with tumor lysis
syndrome in particular diseases, such as fludarabine and lenalidomide
in patients treated for CLL.7,13,19,20 Because the risk of clinical tumor
lysis syndrome is proportional to the rapidity of response to therapy,
patients whose tumors respond quickly to a new therapeutic agent
have an increased risk for the development of tumor lysis syndrome.
Patients with diagnoses not typically associated with tumor lysis
syndrome (e.g., metastatic colon cancer) can also be affected by
tumor lysis syndrome when the treatment includes new, highly active
agents, such as cetuximab.21 To successfully treat and prevent tumor
lysis syndrome, it is necessary to identify patients at risk and tailor
prevention according to risk, as described in the next section.6

PREVENTION AND MANAGEMENT OF TUMOR

LYSIS SYNDROME
Published guidelines for the diagnosis, prevention, and management
of tumor lysis syndrome (Table 38-2) differ in many details. However,
all guidelines agree that patients at risk for tumor lysis syndrome
should undergo risk stratification and management on the basis of
their risk. Clinical tumor lysis syndrome is the outcome that should
be prevented, because by definition it is associated with morbidity.
Standard prophylaxis includes close monitoring, hyperhydration to
increase urine output and facilitate renal excretion of uric acid and
phosphorus, and administration of a hypouricemic agent, such as
allopurinol or rasburicase, to prevent the formation of uric acid
crystals in the kidney, as well as administration of phosphate binders
to reduce calcium phosphate precipitation in the kidneys.1,2,4,22
Both allopurinol and rasburicase have been used successfully to
reduce the incidence of tumor lysis syndrome in pediatric and adult
patients.1,23 Historically, urine has been alkalinized by the administration of bicarbonate to improve the solubility of uric acid (Fig.
38-2)21,24; however, this step is not currently recommended, because
the solubility of calcium phosphate decreases at higher pH values
(Fig. 38-2), and therefore precipitation in the renal tubules may be
exacerbated. As an alternative to urine alkalinization, the prophylactic
administration of rasburicase has been shown to effectively reduce
uric acid levels.7
All patients at intermediate or high risk for clinical tumor lysis
syndrome should receive hyperhydration with intravenous fluids at
2500mL/m2/day or higher with a goal of very high urine output to
reduce the risk of uric acid and calcium-phosphate precipitation in
renal tubules. If urine output is inadequate even after hyperhydration,
a diuretic may be added to increase urine output, but only after the
patient is very well hydrated.1 Patients at intermediate or high risk
should be monitored in the hospital with serum electrolytes and uric
measurement every 8 to 12 hours (intermediate risk) or 4 to 6 hours
(high risk). Patients who present with tumor lysis syndrome should
be connected to a cardiac monitor and observed in an intensive care
or step-down unit.1

Allopurinol
Allopurinol inhibits xanthine oxidase and prevents metabolism of
hypoxanthine and xanthine into uric acid, thus reducing the formation of uric acid and the incidence of tumor lysis syndrome when

used prior to the initiation of chemotherapy (Fig. 38-3).4,25 However,

allopurinol has several limitations. Allopurinol therapy is most effective when it is used 24 to 48 hours before the start of chemotherapy,
which may cause a delay in the initiation of cytotoxic therapy.22
Furthermore, it does not remove existing uric acid, which is a significant problem in patients who present with significant hyperuricemia.
Finally, treatment with allopurinol increases xanthine concentrations
in the urine, which can cause xanthine crystal formation and
nephropathy.26 Hande and colleagues27 examined purine excretion in
11 patients with bulky lymphomas. All patients received allopurinol
2 to 5 days before chemotherapy. Although urinary concentrations
of uric acid and hypoxanthine remained below solubility in all
patients, concentrations of xanthine exceeded solubility in 6 patients
(55%). Purine metabolism was studied in 19 children with ALL who
received allopurinol for the prevention of tumor lysis syndrome
before starting chemotherapy.28 Xanthine exceeded urine solubility in
16 patients (84%). Because xanthine is rarely measured, its contribution to tumor lysis syndrome remains unknown,29 but its low solubility at all urine pH values and high concentrations in the urine of
patients treated with allopurinol suggest that xanthine nephropathy
may occur commonly in patients with a high cancer cell mass, who
produce large amounts of purines after initiation of chemotherapy.

Rasburicase
Rasburicase converts uric acid into allantoin, a highly soluble metabolite that is excreted by the kidneys (see the light green line in Fig.
38-2). Unlike most other mammals, humans lack a functional urate
oxidase enzyme because of a nonsense mutation in the genetic
sequence. Rasburicase lowers serum uric acid levels quickly and has
few adverse effects (Fig. 38-1).1,23,30 However, rasburicase is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency because of the high risk of the development of
methemoglobinemia and hemolytic anemia after receiving these
agents, because of the breakdown of uric acid into hydrogen
peroxide.1
In an effort to reduce costs, some clinicians administer lower doses
of rasburicase than the 0.15 to 0.2mg/kg approved by the U.S. Food
and Drug Administration (FDA), in the hope that the lower dose
will effectively prevent or manage tumor lysis syndrome. Although
no clinical trial results have validated the efficacy of this approach,
several retrospective studies and case reports have been published in
which lower doses of rasburicase were used successfully. Lee and colleagues31 used a 4.5-mg fixed dose to treat three children with ALL.
All three patients had a rapid reduction in uric acid, but when the
weight-adjusted dose was determined for the 4.5-mg dose, it was
found that one patient received a higher quantity than the FDAapproved dose (0.26mg/kg), one patient received the approved dose
(0.17mg/kg); and one patient received 50% of the approved dose
(0.08mg/kg). Another case series examined 11 adults with hematologic malignancies at risk for tumor lysis syndrome.32 Eight patients
had renal impairment as a result of tumor lysis syndrome at the time
of presentation, and all were treated with a 6-mg, single dose of
rasburicase (corresponding to a median weight-based dose of 0.08mg/
kg). In 10 of the 11 patients, single-dose rasburicase lowered and
maintained normal uric acid levels; the mean pretreatment uric acid
level, 11.7mg/dL, was reduced to 2.0mg/dL after treatment. One
morbidly obese patient required a second dose of rasburicase (12mg;
0.046mg/kg, based on actual body weight) to control his uric acid
levels. Among the eight patients with renal impairment, three had a
return to baseline renal function after receiving rasburicase, one
required hemodialysis, and four had no subsequent renal function
data reported. Although the authors concluded that use of a fixed,
6-mg dose of rasburicase appeared to be safe and effective, the fact
that one patient required a large second dose and one required dialysis
implies inadequate uric acid control, especially when compared with
the 98% to 100% efficacy reported in large studies using the

594

Part II: Problems Common to Cancer and Its Therapy

Table 38-2 Published Guidelines for Risk Classification and Management of Tumor Lysis Syndrome
Source

Type of Tumor
Lysis Syndrome

Cancer-Associated
Risk Factors

This chapter

Clinical

ASCO22

Not specified

Burkitt, lymphoblastic,
or diffuse, large-cell
lymphomas; ALL; solid
tumors with high
proliferative rates and
rapid response to
therapy; bulky disease,
elevated LDH; WBC
count >25,000/L

COG Supportive
Care Guidelines
version
6/20/0838

Not specified

NCCN Practice
Guidelines in
Oncology: AML
and NHL39,40

SFCE41

Patient-Associated
Risk Factors

Definition of
Risk Groups

Management
Recommendations

Established tumor
lysis syndrome
at presentation
or high risk;
intermediate
risk; low risk;
negligible risk

Established tumor lysis

syndrome or high risk:
IVF and rasburicase
Intermediate risk: IVF
and single dose of
rasburicase or daily
allopurinol; close
monitoring
Low risk: clinical
judgment and
monitoring
Negligible risk: no
monitoring or
prophylaxis

Preexisting renal
failure, oliguria, and
hyperuricemia

Low-, intermediate-,
and high-risk
groups based
on specific
combinations of
cancer- and
patient-associated
risk factors

High risk: IVF and

rasburicase
Intermediate risk: IVF and
allopurinol; rasburicase
if hyperuricemia
develops
Low risk: clinical
judgment and
monitoring

Bulky disease; high tumor

burden; chemosensitive
cancers; WBC count
>100,000/L;
lymphadenopathy;
hepatosplenomegaly;
elevated LDH; large
primary masses of the
abdomen, thorax, or
mediastinum; ALL; T-cell
leukemias and
non-Hodgkin
lymphomas

Presentation with
serum creatinine
greater than
0.7mg/dL
(children) or
1.3mg/dL (adults);
hyperuricemia;
signs of evolving
tumor lysis
syndrome

Not defined

Prophylaxis: IVF and

allopurinol daily
Patients with renal
insufficiency, elevated
creatinine, and/or
hyperuricemia:
rasburicase for
1-3 days

Not specified

AML; lymphoblastic
lymphoma; Burkitt
lymphoma; a bulky
presentation of diffuse,
large, B-cell lymphoma;
or chronic lymphocytic
leukemia with high WBC
count

Unable to tolerate
oral medication,
clinical tumor lysis
syndrome, or
problematic
hyperuricemia

Not defined

Prophylaxis: IVF with

alkalinization and
allopurinol
Patients with clinical
tumor lysis syndrome
and/or hyperuricemia:
IVF and consider
rasburicase

Need for additional

rasburicase to
control tumor
lysis syndrome

WBC count >50,000/L;

large tumor burden
(lymph nodes >5cm,
hepatosplenomegaly,
mediastinal mass >5cm);
elevated LDH >2 ULN;
AML; T-cell lymphomas;
B-cell lymphomas;
Burkitt leukemia

Creatinine >ULN for

age and weight,
uric acid >ULN
for age, and
phosphorus >ULN

High risk: presence

of any cancer- or
patient-associated
risk factor
Low risk: absence of
risk factors

High risk: daily

rasburicase for 5 days
Low risk: 1 dose of
rasburicase, then
repeat as needed

Data from references 22 and 38-41.

ALL, Acute lymphocytic leukemia; AML, acute myeloid leukemia; ASCO, American Society of Clinical Oncology; COG, Childrens Oncology Group; IVF, intravenous fluids;
LDH, lactate dehydrogenase; NCCN, National Comprehensive Cancer Network; NHL, non-Hodgkin lymphoma; SFCE, Socit Franaise de Lutte contre les Cancers et Leucmies de
lEnfant et de lAdolescent (French Pediatric Oncology Society); ULN, upper limit of normal; WBC, white blood cell.

Tumor Lysis Syndrome CHAPTER 38 595

Solubility (mg/dL)

1000

100

10

1
4.5

5.5

6
6.5
Urine pH

Allantoin
Hypoxanthine

Uric acid
Calcium phosphate

7.5

Xanthine

Figure 38-2 Solubility of purine metabolites by urine pH. Uric acid

solubility is highly pH dependent. As urine pH rises from 5 to 7, the solubility

increases 25-fold, from 8mg/dL to 200mg/dL. This increased uric acid solubility and consequent decreased risk of crystal formation and acute kidney
injury is the reason urine alkalinization was standard for patients at risk for
tumor lysis syndrome before the advent of rasburicase. In contrast to uric
acid, calcium phosphate becomes less soluble and more likely to crystallize as
urine pH increases. Xanthine has low solubility and hypoxanthine relatively
high solubility, regardless of urine pH. Note that the scale is logarithmic.
(From Howard SC, Ribeiro RC, Pui CH. Acute complications. In: Pui CH,
editor. Childhood leukemias. Cambridge, UK: Cambridge University Press;
2012.)

8
Allopurinol AUC0-96hr = 329 129 mg/dL*hr
Rasburicase AUC0-96hr = 128 70 mg/dL*hr

Uric acid mg/dL

7
6
5
4
3

P < 0.0001

2
1
0
0

Allopurinol
25
Rasburicase 27

12

24

36
48
60
Time (hours)

72

25
25
24
27
27
26
Number of samples at each time point

84

96
22
25

Figure 38-3 Uric acid levels during the first 4 days of treatment

in patients at risk for tumor lysis syndrome who were randomly assigned
to receive rasburicase versus allopurinol. In patients at risk for tumor lysis
syndrome, rasburicase was associated with a rapid decrease in uric acid
and a corresponding lower area under the concentration time curve for uric
acid, as measured during the first 4 days of therapy (128 70 vs. 329
129mg/dL*hour, P < .0001). (Data from Goldman SC etal. A randomized
comparison between rasburicase and allopurinol in children with lymphoma
or leukemia at high risk for tumor lysis. Blood 2001;97(10):29983003.)

FDA-approved dose.11 Another report describes an obese woman

with chronic myelomonocytic leukemia in blast crisis who was treated
with 11mg of rasburicase (a dose based on her ideal body weight),
which adequately controlled her uric acid.33
Two retrospective studies of reduced-dose rasburicase have
been reported recently.34,35 A fixed rasburicase dose of 3mg, with
repeated doses as needed based on subsequent uric acid levels, was

administered to 43 adult patients undergoing stem cell transplantation (51%) or receiving chemotherapy (49%).34 The total doses of
rasburicase administered were 3mg (n = 37), 4.5mg (n = 2), or 6mg
(n = 4), and uric acid levels were all within normal limits 48 hours
after the first dose. Although three patients were already receiving
dialysis at the time of the study, no additional patients required dialysis. What is not clear from this study is whether the patients were at
risk for tumor lysis syndrome. Many patients undergoing stem cell
transplantation already have a low bulk of disease and would not be
expected to have tumor lysis syndrome, and the disease status of the
patients in the study cohort was not described. The second cohort in
which use of a reduced-dose of rasburicase was evaluated included 46
adults with hematologic cancers and four with solid tumors.35 Patients
were eligible to receive rasburicase if they had bulky disease, an elevated white blood cell count, elevated lactate dehydrogenase in addition to elevated uric acid, or a history of tumor lysis syndrome after
a prior course of chemotherapy. Rasburicase dosing was at the discretion of the treating clinician, and the initial dose ranged from 1.5 to
16.5mg. Nine patients had uric acid levels above the normal range
after the initial rasburicase dose, despite a mean decrease of 41% from
their baseline levels. Because of the heterogeneous cohort of patients
(diagnoses included ALL, acute myeloid leukemia, CLL, myeloma,
solid tumors, and both high- and low-grade lymphomas) and the
wide range of rasburicase doses used, it is difficult to derive specific
treatment recommendations from the data presented. However, the
results do suggest that using doses of rasburicase that are lower than
recommended may be effective for some patients.
The use of reduced doses of rasburicase should be studied in
defined cohorts of patients at an intermediate risk for the development of clinical tumor lysis syndrome to determine the optimal dose
(i.e., the dose at which no patient experiences acute kidney injury or
clinical tumor lysis syndrome and at which the least amount of rasburicase is used). In patients receiving low-dose rasburicase to prevent
tumor lysis syndrome, serum uric acid levels must be measured precisely. Blood samples must be collected into chilled tubes, placed on
ice immediately, and assayed promptly to avoid ex vivo breakdown
of uric acid by rasburicase, which produces artificially low levels of
uric acid.36
Although the optimal treatment for patients at intermediate risk
for clinical tumor lysis syndrome has not been determined by randomized clinical trials, a prudent approach at present is the administration of one standard dose of rasburicase (0.15mg/kg), especially
if hyperuricemia or laboratory tumor lysis syndrome develops.
Patients at high risk for the development of tumor lysis syndrome
should receive at least one standard dose of rasburicase. Repeat doses
of rasburicase should be given to patients with elevated uric acid
levels, and all patients with laboratory tumor lysis syndrome should
receive at least one standard dose of rasburicase (0.15mg/kg) to
prevent progression to clinical tumor lysis syndrome. Although this
strategy has not been validated by a prospective randomized trial, the
one randomized trial comparing rasburicase to allopurinol documented improved creatinine during the first 4 days of therapy
in patients receiving rasburicase but not in patients receiving
allopurinol.37

CONCLUSIONS
Appropriate management of tumor lysis syndrome includes risk
stratification of all patients; hydration; careful monitoring of serum
metabolite levels; administration of rasburicase for patients at intermediate or high risk; and administration of allopurinol for patients
at low risk of clinical tumor lysis syndrome. Hyperuricemia and
hyperphosphatemia should be prevented and treated promptly when
they do occur, because their deposition in the renal tubules can cause
acute kidney injury. Risk-stratified management improves outcomes
by preventing seizures, cardiac dysrhythmia, acute kidney injury, and
the need for dialysis.

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