Tumor Lysis Syndrome: Pathogenesis, Clinical Manifestations, Definition, Etiology and Risk Factors - UpToDate

Tumor lysis syndrome: Pathogenesis, clinical manifestations, definition, etiology and risk factors - UpToDate 13/02/23, 16:24
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Tumor lysis syndrome: Pathogenesis, clinical

manifestations, definition, etiology and risk factors
Authors: Richard A Larson, MD, Ching-Hon Pui, MD
Section Editors: Reed E Drews, MD, Arnold S Freedman, MD, David G Poplack, MD
Deputy Editor: Alan G Rosmarin, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2023. | This topic last updated: May 24, 2022.
INTRODUCTION
Tumor lysis syndrome (TLS) is an oncologic emergency that is caused by massive tumor cell
lysis with the release of large amounts of potassium, phosphate, and nucleic acids into the
systemic circulation. Catabolism of the nucleic acids to uric acid leads to hyperuricemia, and
the marked increase in uric acid excretion can result in the precipitation of uric acid in the
renal tubules and can also induce renal vasoconstriction, impaired autoregulation, decreased
renal blood flow, and inflammation, resulting in acute kidney injury. Hyperphosphatemia
with calcium phosphate deposition in the renal tubules can also cause acute kidney injury
and in the cardiac conduction system can result in arrhythmias.
TLS most often occurs after the initiation of cytotoxic therapy in patients with high-grade
lymphomas (particularly the Burkitt subtype) and acute lymphoblastic leukemia. However,
TLS can occur spontaneously and with other tumor types that have a high proliferative rate,
large tumor burden, or high sensitivity to cytotoxic therapy.
The pathogenesis, definition, classification, risk factors, etiology, and clinical presentation of
TLS will be reviewed here. Prevention and treatment of TLS are discussed elsewhere, as are
issues related to treatment of the particular malignancies that are associated with TLS. (See
"Tumor lysis syndrome: Prevention and treatment" and "Treatment of Burkitt
leukemia/lymphoma in adults" and "Treatment and prognosis of adult T cell leukemia-
lymphoma" and "Overview of the complications of acute myeloid leukemia", section on
'Tumor lysis syndrome' and "Treatment of acute lymphoblastic leukemia/lymphoma in
children and adolescents", section on 'Complications of ALL/LBL and treatment'.)
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PATHOGENESIS
In the setting of a malignancy with a high proliferative rate, large tumor burden, and/or a
high sensitivity to treatment, initiation of cytotoxic chemotherapy, cytolytic antibody therapy,
radiation therapy, or sometimes glucocorticoid therapy alone can result in the rapid lysis of
tumor cells. With the emergence of new effective and targeted anticancer drugs or new
combinations of drugs, TLS has also been observed in patients with cancers that were
previously rarely associated with this complication. (See 'Etiology and risk factors' below.)
This releases massive quantities of intracellular contents (potassium, phosphate, and nucleic
acids that can be metabolized to uric acid) into the systemic circulation. The metabolic
consequences include hyperkalemia, hyperphosphatemia, secondary hypocalcemia,
hyperuricemia, and acute kidney injury. High levels of both uric acid and phosphate increase
the severity of acute kidney injury because uric acid precipitates readily in the presence of
calcium phosphate crystals, and calcium phosphate precipitates readily in the presence of
uric acid crystals.
Hyperuricemia — Hyperuricemia is a consequence of the catabolism of purine nucleic acids

to hypoxanthine and xanthine, and then to uric acid via the enzyme xanthine oxidase
( figure 1). Uric acid is poorly soluble in water, particularly in the usually acidic environment
in the distal tubules and collecting system of the kidney. Overproduction and overexcretion
of uric acid in TLS can lead to crystal precipitation and deposition in the renal tubules, and
acute uric acid nephropathy with acute kidney injury. (See "Uric acid kidney diseases".)
With the development of effective hypouricemic agents, allopurinol and especially

rasburicase, hyperuricemia is no longer the major metabolic complication associated with
TLS [1,2]. (See "Tumor lysis syndrome: Prevention and treatment", section on 'Hypouricemic
agents' and "Tumor lysis syndrome: Prevention and treatment", section on 'Clinical impact of
tumor lysis syndrome'.)
As an example, in a report of 102 patients with intermediate- to high-grade non-Hodgkin

lymphoma (NHL) who received aggressive combination chemotherapy with allopurinol
prophylaxis, laboratory abnormalities developed in 42 percent of the patients, and 6 percent
developed "clinical" TLS [1]. With the prophylactic use of allopurinol, the serum uric acid
concentration rose by more than 25 percent in 28 patients, and the peak exceeded the upper
limit of normal (8 mg/dL [476 micromol/L]) in nine patients and exceeded 15 mg/dL (893
micromol/L) in three patients, one of whom developed acute kidney injury. In another study
of 100 adult patients with aggressive NHL who received rasburicase for prophylaxis during
the first course of chemotherapy, all patients had normal uric acid levels throughout
chemotherapy, even though 11 percent presented with hyperuricemia at the time of
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chemotherapy, even though 11 percent presented with hyperuricemia at the time of

diagnosis [3].
Hyperphosphatemia — The phosphorus concentration in malignant cells is up to four times

higher than in normal cells. Thus, rapid tumor breakdown often leads to
hyperphosphatemia, which can cause secondary hypocalcemia, leading to tetany or seizures.
When the calcium concentration times phosphate concentration (the calcium phosphate
product) exceeds 60 mg2/dL2, there is an increased risk of calcium phosphate precipitation in
the renal tubules, which can lead to acute kidney injury. In addition, precipitation in the heart
may lead to cardiac arrhythmias. Renal replacement therapy may be needed if the calcium
phosphate product is ≥70 mg2/dL2. (See "Overview of the causes and treatment of
hyperphosphatemia" and "Tumor lysis syndrome: Prevention and treatment", section on
'Indications for renal replacement therapy'.)
Since the widespread use of hypouricemic agents, calcium phosphate deposition

(nephrocalcinosis), rather than hyperuricemia, has become the major mechanism of acute
kidney injury in TLS [1,4,5]. (See "Tumor lysis syndrome: Prevention and treatment", section
on 'Hypouricemic agents' and "Tumor lysis syndrome: Prevention and treatment", section on
'Clinical impact of tumor lysis syndrome'.)
Xanthinuria — Allopurinol blocks the catabolism of hypoxanthine and xanthine, leading to

an increase in the levels of these metabolites ( figure 1). Xanthine is much less soluble than
uric acid, and urinary alkalinization increases the solubility of xanthine much less than the
solubility of uric acid because the pKa is much higher for xanthine (7.4 versus 5.8) [6].
Thus, patients with massive TLS who are receiving allopurinol are at risk for xanthine
precipitation in the tubules, resulting in xanthine nephropathy or xanthine stone formation
[7-11]. Because the serum xanthine level is not routinely measured, its effect on the risk of
acute kidney injury is not certain. In contrast to the effect of allopurinol, xanthine
concentration is not increased by rasburicase (recombinant urate oxidase), which is now
preferred in most patients at high risk for TLS. Rasburicase promotes the degradation of uric
acid to the much more water-soluble compound allantoin. However, in patients with glucose-
6-phosphate dehydrogenase (G6PD) deficiency, hydrogen peroxide, a breakdown product of
uric acid, can cause methemoglobinemia and, in severe cases, hemolytic anemia. For this
reason, rasburicase is contraindicated in patients with G6PD deficiency. (See "Tumor lysis
syndrome: Prevention and treatment", section on 'Rasburicase'.)
CLINICAL MANIFESTATIONS
The symptoms associated with TLS largely reflect the associated metabolic abnormalities
The symptoms associated with TLS largely reflect the associated metabolic abnormalities
(hyperkalemia, hyperphosphatemia, and hypocalcemia). They include nausea, vomiting,
diarrhea, anorexia, lethargy, hematuria, heart failure, cardiac dysrhythmias, seizures, muscle
cramps, tetany, syncope, and possible sudden death [12].
Acute uric acid or calcium phosphate deposition does not usually cause symptoms referable
to the urinary tract, although flank pain can occur if there is renal pelvic or ureteral stone
formation. The urinalysis classically shows many uric acid crystals or amorphous urates in an
acid urine ( picture 1), but is occasionally relatively normal due to lack of output from the
obstructed nephrons.
DEFINITION AND CLASSIFICATION
Although there is a general consensus that TLS represents a set of metabolic complications
that arise from treatment of a rapidly proliferating and drug-sensitive neoplasm, there have
been relatively few attempts to specifically define the syndrome [13,14]. The 1993 Hande-
Garrow classification system distinguished between laboratory versus clinical TLS within four
days of initial anticancer treatment, but did not take into account patients who already had
abnormal laboratory values prior to treatment or those who developed metabolic
abnormalities at a later time point [1].
Cairo-Bishop definition — The Cairo-Bishop definition, proposed in 2004, provided specific

laboratory criteria for the diagnosis of TLS both at presentation and within seven days of
treatment [14]. It also incorporated a grading system to help delineate the degree of severity
of TLS.
● Laboratory TLS was defined as any two or more abnormal serum values (either a value
above the upper limit of normal [ULN] or a 25 percent increase in the serum value over
baseline), as outlined in the table ( table 1), present within three days before or seven
days after instituting chemotherapy in the setting of adequate hydration (with or
without alkalinization) and use of a hypouricemic agent.
● Clinical TLS was defined as laboratory TLS plus one or more of the following that was
not directly or probably attributable to a therapeutic agent: increased serum creatinine
concentration (≥1.5 times the ULN), cardiac arrhythmia/sudden death, or a seizure.
A grading system for severity of TLS (on a scale from zero to five) in patients with laboratory
TLS was based on the degree of elevation in serum creatinine, the presence and type of
cardiac arrhythmia, and the presence and severity of seizures ( table 2). This scheme for
grading severity is far more useful than the most recent modification of the widely used
National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03),
which only grades TLS as grade 3 (present), grade 4 (life-threatening consequences; urgent
intervention indicated), or grade 5 (death) [15].
The Cairo-Bishop classification has been adopted by the Children's Oncology Group for use in
treatment protocols for advanced stage lymphoma and by an international panel of experts
assembled to establish evidence-based guidelines for prevention and treatment of pediatric
and adult TLS [12,16] (see "Tumor lysis syndrome: Prevention and treatment" and "Tumor
lysis syndrome: Prevention and treatment", section on 'Clinical impact of tumor lysis
syndrome'). In a review, Howard et al suggested that two or more laboratory abnormalities
should be present simultaneously to define laboratory TLS and that any symptomatic
hypocalcemia should constitute clinical TLS [17].
ETIOLOGY AND RISK FACTORS
The risk of TLS is greatest in patients treated for hematologic malignancies but is not
uniform among these disorders ( table 3).
Certain intrinsic tumor-related factors are associated with a higher risk. These include
[1,12,14,16-20]:
● High tumor cell proliferation rate

● Chemosensitivity of the malignancy
● Large tumor burden, as manifested by bulky disease >10 cm in diameter and/or a white
blood cell count >50,000 per microL, a pretreatment serum lactate dehydrogenase
(LDH) more than two times the upper limit of normal, organ infiltration, or bone
marrow involvement
There are also clinical features that predispose to the development of TLS [1,12,14,16,17,19]:
● Pretreatment hyperuricemia (serum uric acid >7.5 mg/dL [446 micromol/L]) or

hyperphosphatemia (serum phosphate >4.5 mg/dL [1.44 micromol/L])
● A preexisting nephropathy or exposure to nephrotoxins
● Oliguria and/or acidic urine
● Dehydration, volume depletion, or inadequate hydration during treatment
The importance of impaired renal function as a risk factor for TLS was illustrated in a series of
102 patients with high-grade non-Hodgkin lymphoma (NHL) [1]. Patients with a baseline
serum creatinine >1.5 mg/dL (133 micromol/L) had a markedly higher rate of clinical TLS than
did those with a lower serum creatinine (36 versus 2 percent).
Hematologic malignancies — The tumors most frequently associated with TLS are clinically
Hematologic malignancies — The tumors most frequently associated with TLS are clinically
aggressive NHLs and acute lymphoblastic leukemia (ALL), particularly Burkitt
lymphoma/leukemia ( table 3) [1,18,21-25], and chronic lymphocytic leukemia (CLL).
The incidence of TLS in these patients can be illustrated by the following reports:
● In the series cited above of 102 adults with high-grade NHL, most of whom received
prophylaxis with allopurinol alone, the overall incidence of TLS was 42 percent, and 6
percent developed "clinical" TLS [1]. Clinical TLS was defined in this series as serum
potassium >6 mEq/L, serum creatinine >2.5 mg/dL [221 micromol/L], serum calcium ≤6
mg/dL [1.5 mmol/L], the development of a life-threatening arrhythmia, or sudden
death.
● The incidence of TLS was assessed in a series of children with advanced stage Burkitt
lymphoma/leukemia who were enrolled in two multicenter trials [18]. All were treated
with aggressive intravenous hydration, urinary alkalinization (urine pH 7), and
allopurinol, but not rasburicase, which was not available at that time. Among the 218
evaluable children with Burkitt ALL or stage III/IV Burkitt lymphoma with a high
pretreatment serum LDH (≥500 U/L [8.3 kat/L]), TLS (laboratory and/or clinical)
developed in 16.1 percent and anuria in 9.2 percent.
Other hematologic malignancies that were less commonly associated with TLS (before the
current era of precision medicine) include other clinically aggressive lymphomas, such as
anaplastic large cell lymphoma, T-cell or B-ALL, acute myeloid leukemia (AML), CLL, and
plasma cell disorders, including multiple myeloma and isolated plasmacytomas [1,19,26-30].
The incidence of TLS in AML was addressed in a single institution series of 772 adult patients
who received induction chemotherapy between 1980 and 2002 [19]. Prophylactic measures
included intravenous hydration and allopurinol. Overall, 130 (17 percent) developed TLS (5
percent clinical, 12 percent laboratory, according to the Cairo-Bishop definition described
above). On multivariate analysis, the following pretreatment laboratory findings were
independent risk factors for TLS: serum LDH above laboratory normal values, serum
creatinine ≥1.4 mg/dL (124 micromol/L), pretreatment serum uric acid >7.5 mg/dL (446
micromol/L), and white blood cell count ≥25,000/microL. These four factors were used to
develop a scoring system to predict the development of TLS in AML. (See 'Risk stratification in
acute leukemia' below.)
Most cases of TLS in patients with hematologic malignancies follow treatment with
combination cytotoxic chemotherapy. However, TLS has also been described in case reports
with glucocorticoids alone in patients with NHL and ALL [31,32], with therapeutic monoclonal
antibodies (primarily rituximab in patients with high-grade NHL [22-24] but also bortezomib
antibodies (primarily rituximab in patients with high-grade NHL [22-24] but also bortezomib
in multiple myeloma [29,30]), with imatinib for chronic myeloid leukemia [33], with
venetoclax for CLL or AML, and with radiation therapy alone for NHL and ALL [25,34,35].
The emergence of effective targeted anticancer drugs, used alone or in combination with
conventional cytotoxic agents, has led to an increase in the frequency and severity of TLS in
hematologic cancers that previously were rarely associated with this complication [36],
including:
● Venetoclax, a B-cell lymphoma 2 inhibitor used for CLL and AML. (See "Treatment of
relapsed or refractory chronic lymphocytic leukemia", section on 'BCL2 inhibitors:
Venetoclax' and "Acute myeloid leukemia: Management of medically-unfit adults".)
● Obinutuzumab (anti-CD20 monoclonal antibody), which is approved for use in relapsed

or refractory diffuse large B-cell lymphoma. (See "Diffuse large B cell lymphoma
(DLBCL): Suspected first relapse or refractory disease in medically-fit patients".)
● Dinaciclib (an experimental cyclin-dependent kinase inhibitor) for advanced leukemia

and other cancers.
● Alvocidib (flavopiridol, cyclin-dependent kinase inhibitor), which is under study in

combination with cytarabine and mitoxantrone for poor-risk AML
● Chimeric antigen receptor T-cell therapy for lymphoid malignancy [37].
In some cases (eg, venetoclax for CLL), a gradual stepwise dose-escalation strategy has been
used successfully in an effort to reduce the risk of TLS [38-40]. (See "Treatment of relapsed or
refractory chronic lymphocytic leukemia", section on 'BCL2 inhibitors: Venetoclax'.)
Solid tumors — TLS has been rarely described after treatment of nonhematologic solid
tumors [20,41]. These include breast cancer [42-44], small cell carcinoma (mostly involving
the lung) [20,42], neuroblastoma [42], germ cell tumors [20,45], medulloblastoma [20],
sarcoma [20,46], ovarian cancer [47,48], squamous cell carcinoma of the vulva [49],
metastatic colorectal cancer [50], urothelial cancer [51], gastrointestinal stromal tumors [52],
melanoma [20], hepatocellular carcinoma [20,53], renal cell and soft tissue sarcoma treated
with pazopanib [54,55], medullary thyroid cancer treated with selpercatinib [56], and
prostate cancer [57].
Many reports implicate docetaxel [57-59]. Most of the affected patients had extensive or
bulky disease at the time of treatment initiation, and some cases were fatal. The United
States Prescribing Information for docetaxel recommends that patients at risk for TLS (renal
impairment, hyperuricemia, bulky tumor) be closely monitored for TLS before and during
treatment, and correction of dehydration as well as lowering of high serum uric acid levels
treatment, and correction of dehydration as well as lowering of high serum uric acid levels
prior to initiation of docetaxel.
Treatment with pazopanib, a highly albumin bound tyrosine kinase inhibitor had resulted in
TLS in a patient with clear cell renal cell carcinoma and low serum albumin level [55]. The
United States Prescribing Information for pazopanib also recommends that patients at
risk for TLS (eg, rapidly growing tumors, high tumor burden, renal impairment, dehydration)
be closely monitored and treated as clinically indicated. A similar warning is provided in the
United States Prescribing Information for selpercatinib in the treatment of medullary
thyroid cancer.
Spontaneous TLS — Spontaneous acute kidney injury associated with marked

hyperuricemia prior to the initiation of therapy has been described in NHL and acute
leukemia [21,26,60,61], and in at least one patient with inflammatory breast cancer [62]. The
actual incidence of this syndrome is difficult to ascertain. In a series of 33 patients with
aggressive or highly aggressive NHL, three had marked hyperuricemia (plasma uric acid
concentration >17 mg/dL [1012 micromol/L]) and acute kidney injury requiring hemodialysis
prior to the initiation of chemotherapy [21].
Interestingly, spontaneous TLS is associated with hyperuricemia but frequently without

hyperphosphatemia. It has been postulated that rapidly growing neoplasms with high cell
turnover rates produce high serum uric acid levels through rapid nucleoprotein turnover but
that the tumor is able to reutilize released phosphorus for resynthesis of new tumor cells
[26]. By contrast, TLS after chemotherapy is due to cell destruction in the absence of
reuptake of phosphorus and, thus, hyperphosphatemia.
RISK STRATIFICATION
In 2008, an international expert panel published evidence-based guidelines for the

prevention and management of TLS [12], which were subsequently refined and updated [16].
A risk stratification system for TLS was proposed using the type of malignancy, the burden of
disease, treatment, expected response to treatment, and renal function ( table 4). The
recommended therapy varied according to the risk category. Both the stratification system
and the specific treatment recommendations were defined by consensus opinion; neither
has been validated in a prospectively defined group of patients.
High risk — Included in the high-risk group (>5 percent risk of TLS) are [16]:
● All Burkitt leukemia, stage III or IV Burkitt lymphoma or early stage Burkitt lymphoma
with serum lactate dehydrogenase (LDH) level two or more times the upper limit of
normal (≥2 times the upper limit of normal [ULN])
normal (≥2 times the upper limit of normal [ULN])
● Other acute lymphoblastic leukemia (ALL) with a white blood cell (WBC) count ≥100,000
per microL and/or serum LDH level ≥2 times the ULN
● Acute myeloid leukemia (AML) with WBC count ≥100,000 per microL
● Stage III or IV lymphoblastic lymphoma or early stage lymphoblastic lymphoma with

serum LDH level two or more times the upper limit of normal (≥2 times the ULN)
● Chronic lymphocytic leukemia (CLL) treated with venetoclax and lymph node ≥10 cm or
lymph nodes ≥5 cm plus absolute lymphocyte count ≥25 x 109/L, and elevated serum
uric acid level
● Adult T-cell lymphoma/leukemia, diffuse large B-cell lymphoma, peripheral T-cell

lymphoma, transformed lymphoma, or mantle cell lymphoma with serum LDH level
above the ULN and a bulky tumor mass
● Stage III or IV childhood diffuse large B-cell lymphoma with serum LDH level ≥2 times
the ULN
● Patients with intermediate-risk disease with renal dysfunction and/or renal involvement
or uric acid, potassium, or phosphate levels above the ULN
In keeping with the recommendations of the expert panel [12], we recommend that all
patients that fit into these high-risk categories receive aggressive intravenous (IV) hydration
and prophylactic rasburicase, rather than allopurinol, prior to treatment initiation (unless
they have glucose-6-phosphate dehydrogenase deficiency). (See "Tumor lysis syndrome:
Prevention and treatment", section on 'Rasburicase' and "Tumor lysis syndrome: Prevention
and treatment", section on 'Contraindications and restrictions'.)
Other definitions for high risk have been proposed. As an example, the French Society
Against Cancers and Leukemias of Children and Adolescents classifies children as at high risk
for TLS if they have one of the following: leukocyte count >50,000 per microL, large tumor
burden (major hepatomegaly or splenomegaly, lymph nodes or a mediastinal mass >5 cm),
T-cell or B-cell lymphoma, L3 ALL (Burkitt leukemia), AML, any other leukemia with serum
LDH >2 times the ULN, creatinine >ULN for age and weight, uric acid ≥300 micromol/L if ≤10
years of age or ≥350 micromol/L if >10 years old, and serum phosphorus level >2 mmol/L
[63]. They recommend that all such patients receive rasburicase 0.2 mg/kg per day for five
days.
Intermediate risk — The intermediate-risk group (risk of TLS 1 to 5 percent) includes [16]:


lymphoma, transformed lymphoma, or mantle cell lymphoma with serum LDH level
above the ULN but without bulky disease
● Stage III or IV childhood anaplastic large cell lymphoma with serum LDH level <2 times
the ULN
● Early stage Burkitt lymphoma with serum LDH level <2 times the ULN
● ALL with WBC <100,000/microL and serum LDH level <2 times the ULN
● AML with WBC 25,000 to 100,000/microL or AML with WBC <25,000/microL and LDH ≥ 2
times the ULN
● Early stage lymphoblastic lymphoma with serum LDH level <2 times the ULN
● CLL/small lymphocytic lymphoma (SLL) treated with fludarabine, rituximab, or

lenalidomide, or venetoclax with lymph nodes ≥5 cm or an absolute lymphocyte count
≥25 x 109/L, and/or those with a high WBC count (≥50,000/microL)
● Rare bulky solid tumors that are highly sensitive to chemotherapy (such as
neuroblastoma, germ cell cancer, small cell lung cancer)
However, there is disagreement among experts as to the overall risk of TLS with CLL/SLL.
Some clinicians consider that patients with CLL/SLL and a WBC count between 10,000 and
50,000/microL are at relatively low risk for TLS, regardless of treatment, while others consider
all patients with CLL/SLL to be at risk for TLS if they have a WBC ≥50,000, or low circulating
WBC counts and a packed marrow, particularly if they are older and have borderline renal
function. Although initially reported with fludarabine and rituximab, there are now several
reports of TLS occurring after lenalidomide, flavopiridol, or venetoclax therapy for relapsed
or fludarabine-refractory CLL [38,64,65]. (See "Treatment of relapsed or refractory chronic
lymphocytic leukemia".)
In keeping with the recommendations of the expert panel, we generally use allopurinol,
rather than rasburicase, for prophylaxis in most of these patients in the absence of
pretreatment hyperuricemia. An alternative approach is administration of a single dose of
rasburicase [66,67]. (See "Tumor lysis syndrome: Prevention and treatment", section on
'Allopurinol' and "Tumor lysis syndrome: Prevention and treatment", section on 'Dosing and
administration'.)
Some clinicians routinely place all CLL/SLL patients on allopurinol prior to initial
chemotherapy, and treatment protocols from the Cancer and Leukemia Group B (CALGB)
routinely recommend allopurinol 300 mg daily for the first 14 days of chemotherapy,
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routinely recommend allopurinol 300 mg daily for the first 14 days of chemotherapy,
thereafter at the clinician's discretion. However, as noted above, most patients with CLL and a
WBC count 10,000 to 50,000/microL have a relatively low risk of TLS, regardless of treatment,
and others approach these patients with hydration and close monitoring rather than routine
prophylaxis with any hypouricemic agent. In our view, treatment of these patients should be
individualized based upon circulating WBC count, status of the bone marrow, and renal
function, especially with the use of newer targeted therapies, such as venetoclax. The
United States Prescribing Information for venetoclax recommends prophylactic
allopurinol, even in those patients predicted to be at low risk of TLS.
A debulking strategy and dose ramp-up approach have been used in the treatment of
patients with intermediate- or high-risk CLL receiving venetoclax [68]. In a study of 80
previously untreated patients with high-risk CLL, in whom ibrutinib monotherapy was given
for three cycles followed by the addition of venetoclax in the fourth cycle, only three patients
developed laboratory evidence of TLS [69]. Notably, among patients with AML, significant
reduction of venetoclax dose is recommended when used in combination with other
chemotherapy agents and azole antifungal drugs, which are strong CYP3A inhibitors
( table 5), since coadministration can lead to seven- to ninefold increase in venetoclax level
[70].
Low risk — Patients at low risk for TLS (<1 percent risk) include [16]:
● AML with WBC count <25,000/microL and serum LDH level <2 times the ULN
● CLL/SLL with a WBC count ≤50,000/microL and not treated with fludarabine/rituximab
or venetoclax
● Multiple myeloma and chronic myelogenous leukemia (CML)
● Other adult non-Hodgkin lymphomas that do not meet the criteria for high risk or
intermediate risk, with serum LDH level within normal limits
● Other solid tumors
We generally recommend hydration but do not administer any form of prophylactic

hypouricemic therapy or phosphate binders to patients in the low-risk category. This is in
agreement with the expert panel recommendation for a "watch and wait" approach with
close monitoring, rather than routine prophylaxis, in these patients [16]. (See "Tumor lysis
syndrome: Prevention and treatment", section on 'Prevention'.)
Risk stratification in acute leukemia — Predictive models for the probability of TLS in

patients treated for AML or pediatric ALL have been developed [19,71,72]. As previously
described, a scoring system to predict TLS was developed and validated in a series of 772
adult patients with AML treated at a single institution over a 22-year period [19]. (See
'Hematologic malignancies' above.)
The patients were randomly divided into two groups; the prognostic model was developed in
one group and validated in the other. In multivariate analysis, four pretreatment laboratory
findings were independent risk factors for TLS: serum LDH above laboratory normal values,
serum creatinine ≥1.4 mg/dL (124 micromol/L), pretreatment serum uric acid >7.5 mg/dL
(446 micromol/L), and WBC count ≥25,000/microL. French-American-British classification was
not an independent predictor of TLS. (See "Classification of acute myeloid leukemia (AML)".)
The authors assigned a point value to these factors and developed a scoring system to
predict the probability of clinical TLS ( table 6):
● Score 0 – 0 percent
● Score 1 – 1.4 percent
The authors suggested that the model might permit risk-adapted management of TLS in
AML, specifically the selection of those high-risk patients who should receive prophylactic
rasburicase. However, they did not make a specific recommendation as to which score should
be used as the cutoff for the use of rasburicase versus allopurinol. In general, these models
are complex, and they lack standardized guidelines for supportive care guidelines. We
generally prefer the risk stratification system proposed by the expert consensus panel
( table 4) [12]. Prevention and treatment of TLS according to estimated risk of TLS are
discussed in detail elsewhere. (See "Tumor lysis syndrome: Prevention and treatment".)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Tumor lysis
syndrome".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview
and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles on
a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Tumor lysis syndrome (The Basics)")
SUMMARY AND RECOMMENDATIONS
● Pathogenesis, clinical manifestations, and definition
• Tumor lysis syndrome (TLS) is an oncologic emergency that is caused by massive

tumor cell lysis and the release of large amounts of potassium, phosphate, and uric
acid into the systemic circulation. Deposition of uric acid and/or calcium phosphate
crystals in the renal tubules can result in acute kidney injury. (See 'Pathogenesis'
above.)
• The symptoms associated with TLS largely reflect the associated metabolic
abnormalities (hyperkalemia, hyperphosphatemia, and hypocalcemia). They include
nausea, vomiting, diarrhea, anorexia, lethargy, hematuria, heart failure, cardiac
dysrhythmias, seizures, muscle cramps, tetany, syncope, and possible sudden death.
(See 'Clinical manifestations' above.)
• The Cairo-Bishop definition for TLS is commonly used (see 'Cairo-Bishop definition'
above):
- Laboratory TLS is defined as any two or more of the following metabolic

abnormalities and presents within three days before or seven days after
instituting chemotherapy: hyperuricemia, hyperkalemia, hyperphosphatemia,

and hypocalcemia ( table 1).
- Clinical TLS is defined as laboratory TLS plus one or more of the following not
Clinical TLS is defined as laboratory TLS plus one or more of the following not
directly or probably attributable to a therapeutic agent: increased serum
creatinine concentration (≥1.5 times the upper limit of normal), cardiac
arrhythmia/sudden death, or a seizure. A grading system for TLS based upon
the severity of clinical TLS is presented in the table ( table 2).
● Etiology and risk factors
• TLS is observed most frequently in patients with high-grade lymphomas (particularly

the Burkitt subtype) and acute lymphoblastic leukemia following the initiation of
cytotoxic therapy, although it may also occur spontaneously and/or in other tumor
types with a high proliferative rate, large tumor burden, or high sensitivity to
cytotoxic therapy. (See 'Etiology and risk factors' above.)
• With the development of effective targeted therapy, TLS is now being reported in
cancers that were only rarely associated with this complication (eg, colon cancer;
chronic lymphocytic leukemia treated with fludarabine, rituximab, lenalidomide, or
venetoclax; chronic myeloid leukemia; and lymphoid malignancies treated with
chimeric antigen receptor T-cell therapy).
● Risk stratification – Risk stratification based upon tumor-related and patient-related

factors can permit an assessment of the risk of TLS, which may assist in selecting
therapy ( table 4). A simplified algorithmic approach to risk stratification for TLS is
presented in the figure ( algorithm 1) [17]. (See 'Risk stratification' above.)
Use of UpToDate is subject to the Terms of Use.
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Topic 1154 Version 37.0
GRAPHICS
Endogenous production of uric acid

Endogenous production of uric acid
Excessive purine catabolism results in the production of

hypoxanthine and xanthine, which are metabolized to uric acid via
the enzymatic action of XO. This pathway can be blocked by the use
of allopurinol, a hypoxanthine analog that competitively inhibits XO,
and febuxostat, a non-purine thiazolecarboxylic acid derivative that
selectively inhibits XO. After about two to three days, allopurinol and
febuxostat result in increased excretion of both hypoxanthine, which
is more soluble than uric acid, and xanthine, which is less soluble
than uric acid. Preformed uric acid is not altered by allopurinol or
febuxostat. UO, present in most mammals but not humans, oxidizes
preformed uric acid to allantoin, which is 5 to 10 times more soluble
than uric acid in acid urine. When exogenous UO (uricase,
rasburicase, pegloticase) is administered, serum and urinary uric
acid levels decrease markedly within approximately four hours.
XO: xanthine oxidase; UO: urate oxidase.

* UO is not normally present in humans.
Graphic 79178 Version 3.0
Uric acid crystals in the urine
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These crystals are pleomorphic, most often appearing as rhombic plates or rosettes. They are yellow or
reddish-brown and form only in an acid urine (pH 5.5 or less).
Courtesy Gary C Curhan, MD, ScD.
Cairo-Bishop definition of laboratory tumor lysis syndrome
Element Value Change from baseline
Uric acid ≥476 micromol/L (8 mg/dL) 25% increase
Potassium ≥6.0 mmol/L (or 6 mEq/L) 25% increase
Phosphorus ≥2.1 mmol/L (6.5 mg/dL) for children or 25% increase
≥1.45 mmol/L (4.5 mg/dL) for adults
Calcium ≤1.75 mmol/L (7 mg/dL) 25% decrease
NOTE: Two or more laboratory changes within three days before or seven days after cytotoxic
therapy.
Reproduced with permission from: Coiffier B, Altman A, Pui CH, et al. Guidelines for the management of pediatric and
adult tumor lysis syndrome: an evidence-based review. J Clin Oncol 2008; 26:2767. Copyright ©2008 American Society of
Clinical Oncology. All rights reserved.
Cairo-Bishop clinical tumor lysis syndrome definition* and grading
Grade
Complication
0 1 2 3 4 5
Creatinine ¶ Δ ≤1.5 × 1.5 × ULN >1.5-3.0 × >3.0-6.0 × >6.0 × ULN Death

ULN ULN ULN
Cardiac None Intervention Nonurgent Symptomatic Life- Death

arrhythmia ¶ not medical and threatening
indicated intervention incompletely (eg,
indicated controlled arrhythmia
medically or associated
controlled with HF,
with device hypotension,
(eg, syncope,
defibrillator) shock)
Seizure ¶ None – One brief, Seizure in Seizure of Death

generalized which any kind
seizure; consciousness which are
seizure(s) is altered; prolonged,
well poorly repetitive or
well poorly repetitive or

controlled controlled difficult to
by seizure control (eg,
antiseizure disorder; with status
medications breakthrough epilepticus,
or generalized intractable
infrequent seizures epilepsy)
focal motor despite
seizures not medical
interfering intervention
with ADL
ULN: upper limit of normal; HF: heart failure; ADL: activities of daily living.
* Clinical tumor lysis syndrome defined as laboratory tumor lysis syndrome plus at least one
clinical complication.
¶ Not directly or probably attributable to therapeutic agent.
Δ If no institutional ULN is specified, age/sex ULN creatinine may be defined as follows: >1 to <12
years of age, both male and female, 61.6 mmol/L; ≥12 to <16 years, both male and female, 88
mmol/L; ≥16 years, female 105.6 mmol/L, male 114.4 mmol/L.
adult tumor lysis syndrome: an evidence-based review. J Clin Oncol 2008; 26:2767. Copyright © 2008 American Society of
Malignancies commonly diagnosed in patients perceived to be at high

risk for developing tumor lysis syndrome
Pediatric Adult Total
Malignancy (n = 682) (n = 387) (n = 1069)
Number Percent Number Percent Number Percent
Acute lymphoblastic 433 63 73 19 506 47

leukemia
Acute myeloid leukemia 74 11 104 27 178 17
Chronic lymphocytic 0 0 37 10 37 3.5

leukemia
Chronic myeloid leukemia 6 0.9 36 9 42 4
Non-Hodgkin's lymphoma 122 18 109 28 231 22
Hodgkin's disease 8 1.2 6 1.6 14 1.3
Multiple myeloma 0 0 15 3.9 15 1.4
Other hematologic 5 0.7 3 0.7 8 0.7

malignancies
Solid tumors 34 5 4 1 38 3.6
NOTE: Data represent consecutive patients enrolled onto a compassionate-use trial evaluating
the efficacy and safety of rasburicase in patients with cancer who presented with, or were at risk
of developing, hyperuricemia.
adult tumor lysis syndrome: an evidence-based review. J Clin Oncol 2008; 26:2767. Copyright ©2008 American Society of
Tumor lysis syndrome (TLS) prophylaxis recommendations based on TLS

risk
Intermediate risk disease

Low risk disease (LRD) High risk disease (HRD)
(IRD)
Most solid tumors Rare, highly chemotherapy- N/A
sensitive solid tumors (eg,
neuroblastoma, germ cell
tumor, small-cell lung cancer)
with bulky or advanced stage
disease
MM Plasma cell leukemia N/A
CML N/A N/A
Indolent NHL N/A N/A
HL N/A N/A
CLL and WBC <50 x 10 9 /L CLL treated with fludarabine, CLL treated with venetoclax
treated only with alkylating rituximab, or lenalidomide, or and lymph node ≥10 cm, or
agents venetoclax and lymph node ≥5 lymph node ≥5 cm and
cm or absolute lymphocyte absolute lymphocyte count
count ≥25 x 10 9 /L, and/or ≥25 x 10 9 /L and elevated
those with high WBC ≥50 x baseline uric acid.
10 9 /L
AML and WBC <25 x 10 9 /L and AML with WBC 25 to 100 x AML and WBC ≥100 x 10 9 /L
LDH <2 x ULN 10 9 /L
AML and WBC <25 x 10 9 /L and

LDH ≥2 x ULN
Adult intermediate grade NHL Adult T cell Adult T cell

and LDH within normal limits leukemia/lymphoma, diffuse leukemia/lymphoma, diffuse
large B-cell, transformed, and large B-cell, transformed, and
mantle cell lymphomas with mantle cell lymphomas with
LDH > ULN, non-bulky bulky disease and LDH ≥2 x
ULN
Adult ALCL Childhood ALCL stage III/IV N/A
N/A Childhood intermediate grade Stage III/IV childhood diffuse
NHL stage III/IV with LDH <2 x large B-cell lymphoma with
ULN LDH ≥2 x ULN
ULN LDH ≥2 x ULN
N/A ALL and WBC <100 x 10 9 /L and Burkitt's leukemia

LDH <2 x ULN
Other ALL and WBC ≥100 x
10 9 /L and/or LDH ≥2 x ULN
N/A Burkitt lymphoma and LDH <2 Burkitt lymphoma stage III/IV
x ULN and/or LDH ≥2 x ULN
N/A Lymphoblastic lymphoma Lymphoblastic lymphoma

stage I/II and LDH <2 x ULN stage III/IV and/or LDH ≥2 x
ULN
N/A N/A Intermediate risk disease with

renal dysfunction and/or renal
involvement
Intermediate risk disease with

uric acid, potassium, and/or
phosphate > ULN
Prophylaxis recommendations
Monitoring Monitoring Monitoring
Hydration Hydration Hydration
±Allopurinol Allopurinol Rasburicase*
N/A: not applicable; MM: multiple myeloma; CML: chronic myeloid leukemia; NHL: non-Hodgkin
lymphoma; HL: Hodgkin lymphoma; CLL: chronic lymphoid leukemia; WBC: white blood cell
count; AML: acute myeloid leukemia; LDH: lactate dehydrogenase; ULN: upper limit of normal;
ALCL: anaplastic large cell lymphoma; ALL: acute lymphoblastic leukemia.
* Contraindicated in patients with a history consistent with glucose-6 phosphate dehydrogenase
(G6PD) deficiency. In these patients, rasburicase should be substituted with allopurinol.
Cairo MS, Coiffier B, Reiter A. Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome
(TLS) in adults and children with malignant diseases: an expert TLS panel consensus. Br J Haematol 2010; 149:578.
Copyright © 2010. Modified with permission of Blackwell Publishing Inc.
Cytochrome P450 3A (including 3A4) inhibitors and inducers
Strong inhibitors Moderate Strong inducers Moderate

inhibitors inducers
Adagrasib Amiodarone* Apalutamide Bexarotene

Atazanavir Aprepitant Carbamazepine Bosentan
Ceritinib Berotralstat Enzalutamide Cenobamate
Ceritinib Berotralstat Enzalutamide Cenobamate

Clarithromycin Cimetidine* Fosphenytoin Dabrafenib
Cobicistat and Conivaptan Lumacaftor Dexamethasone ¶
cobicistat- Crizotinib Lumacaftor- Dipyrone
containing Cyclosporine* ivacaftor Efavirenz
coformulations Mitotane
Diltiazem Elagolix, estradiol,
Darunavir Phenobarbital and norethindrone
Duvelisib
Idelalisib Phenytoin therapy pack Δ
Dronedarone
Indinavir Primidone Eslicarbazepine
Erythromycin
Itraconazole Rifampin Etravirine
Fedratinib
Ketoconazole (rifampicin) Lorlatinib
Fluconazole
Levoketoconazole Mitapivat
Fosamprenavir
Lonafarnib Modafinil
Fosaprepitant*
Lopinavir Nafcillin
Fosnetupitant-
Mifepristone palonosetron Pexidartinib
Nefazodone Grapefruit juice Rifabutin
Nelfinavir Imatinib Rifapentine
Nirmatrelvir- Isavuconazole Sotorasib
ritonavir (isavuconazonium St. John's wort
Ombitasvir- sulfate)
paritaprevir- Lefamulin
ritonavir
Letermovir
Ombitasvir-
Netupitant
paritaprevir-
Nilotinib
ritonavir plus
dasabuvir Ribociclib
Posaconazole Schisandra
Ritonavir and Verapamil

ritonavir-
containing
coformulations
Saquinavir
Telithromycin
Tucatinib
Voriconazole
For drug interaction purposes, the inhibitors and inducers of CYP3A metabolism listed above
can alter serum concentrations of drugs that are dependent upon the CYP3A subfamily of liver
enzymes, including CYP3A4, for elimination or activation.
These classifications are based upon US Food and Drug Administration (FDA) guidance. [1,2]
Other sources may use a different classification system resulting in some agents being
classified differently.
Data are for systemic drug forms. Degree of inhibition or induction may be altered by dose,
method, and timing of administration.
Weak inhibitors and inducers are not listed in this table with exception of a few examples.
Weak inhibitors and inducers are not listed in this table with exception of a few examples.
Clinically significant interactions can occasionally occur due to weak inhibitors and inducers
(eg, target drug is highly dependent on CYP3A4 metabolism and has a narrow therapeutic
index). Accordingly, specific interactions should be checked using a drug interaction program
such as the Lexicomp drug interactions program included within UpToDate.
Refer to UpToDate topics on specific agents and indications for further details.
* Classified as a weak inhibitor of CYP3A4 according to FDA system. [1]
¶ Classified as a weak inducer of CYP3A4 according to FDA system. [1]
Δ The fixed-dose combination therapy pack taken in the approved regimen has moderate CYP3A4
induction effects. When elagolix is used as a single agent, it is a weak CYP3A4 inducer.
Norethindrone and estradiol are not CYP3A4 inducers.
Data from: Lexicomp Online (Lexi-Interact). Copyright © 1978-2023 Lexicomp, Inc. All Rights Reserved.
References:
1. Clinical Drug Interaction Studies — Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions
Guidance for Industry (January 2020) available at: https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/clinical-drug-interaction-studies-cytochrome-p450-enzyme-and-transporter-mediated-drug-
interactions.
2. US Food & Drug Administration. Drug Development and Drug Interactions: Table of Substrates, Inhibitors and
Inducers. Available at: FDA.gov website.
Prognostic factors for CTLS in AML in the training sample: multivariate

analysis and risk scores
CTLS
Co- Unfavorable Regression p
Odds ratio Score
variate categories coefficient value
(95% CI)
WBC ≤25 x 10 9 /L 1.1 1 <0.001 0
25-75 x 10 9 /L 2.7 (1.4-5.4) 1
>75 x 10 9 /L 7.3 (2.0-29.1) 2
Uric acid ≤7.5 mg/dL 2.2 1 <0.001 0
>7.5 mg/dL 9.1 (3.3-26.6) 1
LDH ≤1 x ULN 1.2 1 0.005 0
1-4 x ULN 3.9 (1.5-10.8) 1
>4 x ULN 15.2 (2.2-96.8) 2
LTLS: laboratory tumor lysis syndrome; CTLS: clinical tumor lysis syndrome; WBC: white blood cell
LTLS: laboratory tumor lysis syndrome; CTLS: clinical tumor lysis syndrome; WBC: white blood cell
count; ULN: upper limit of normal.
Reproduced with permission from: Montesinos P, Lorenzo I, Martin G, et al. Tumor lysis syndrome in patients with acute
myeloid leukemia: identification of risk factors and development of a predictive model. Haematologica 2008; 93:9.
Copyright ©2008 Ferrata-Storti Foundation.
Algorithmic approach to risk assessment of tumor lysis syndrome
TLS: tumor lysis syndrome; ULN: upper limit of normal; ICU: intensive care unit.
Modified from Howard SC, Jones DP, Pui CH. The Tumor Lysis Syndrome. N Engl J Med 2011; 364:1844.
Contributor Disclosures
Richard A Larson, MD Grant/Research/Clinical Trial Support: Astellas [Leukemia];Celgene
[Leukemia];Cellectis [Leukemia];Daiichi Sankyo [Leukemia];Gilead [Leukemia];Novartis [Leukemia];Raphael
Pharmaceuticals [Leukemia]. Consultant/Advisory Boards: Actinium Pharma [Leukemia];Celgene Data
Safety Monitoring Board [Leukemia];CVS/Caremark [Leukemia];Epizyme Data Safety Monitoring Board
[Lymphoma];Novartis [Leukemia];Takeda Data Safety Monitoring Board [Leukemia]. All of the relevant
financial relationships listed have been mitigated. Ching-Hon Pui, MD Grant/Research/Clinical Trial
Support: Amgen [Cancer treatment]; Servier [Cancer treatment]. Consultant/Advisory Boards: Adaptive
Biotechnologies [Minimal residual disease detection]; Erytech [Development of eryaspase]; Novartis [Data
safety monitoring committee]. All of the relevant financial relationships listed have been mitigated. Reed E
Drews, MD No relevant financial relationship(s) with ineligible companies to disclose. Arnold S
Freedman, MD Other Financial Interest: Bayer [Lymphoma DSMB]. All of the relevant financial
relationships listed have been mitigated. David G Poplack, MD No relevant financial relationship(s) with
ineligible companies to disclose. Alan G Rosmarin, MD No relevant financial relationship(s) with ineligible
companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.
Conflict of interest policy

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Tumor lysis syndrome: Pathogenesis, clinical manifestations, definition, etiology and risk factors - UpToDate 13/02/23, 16:24

Official reprint from UpToDate®

Tumor lysis syndrome: Pathogenesis, clinical

Hyperuricemia — Hyperuricemia is a consequence of the catabolism of purine nucleic acids

With the development of effective hypouricemic agents, allopurinol and especially

As an example, in a report of 102 patients with intermediate- to high-grade non-Hodgkin

chemotherapy, even though 11 percent presented with hyperuricemia at the time of

Hyperphosphatemia — The phosphorus concentration in malignant cells is up to four times

Since the widespread use of hypouricemic agents, calcium phosphate deposition

Xanthinuria — Allopurinol blocks the catabolism of hypoxanthine and xanthine, leading to

DEFINITION AND CLASSIFICATION

Cairo-Bishop definition — The Cairo-Bishop definition, proposed in 2004, provided specific

ETIOLOGY AND RISK FACTORS

● High tumor cell proliferation rate

● Pretreatment hyperuricemia (serum uric acid >7.5 mg/dL [446 micromol/L]) or

● Obinutuzumab (anti-CD20 monoclonal antibody), which is approved for use in relapsed

● Dinaciclib (an experimental cyclin-dependent kinase inhibitor) for advanced leukemia

● Alvocidib (flavopiridol, cyclin-dependent kinase inhibitor), which is under study in

● Chimeric antigen receptor T-cell therapy for lymphoid malignancy [37].

Spontaneous TLS — Spontaneous acute kidney injury associated with marked

Interestingly, spontaneous TLS is associated with hyperuricemia but frequently without

In 2008, an international expert panel published evidence-based guidelines for the

normal (≥2 times the upper limit of normal [ULN])

● Stage III or IV lymphoblastic lymphoma or early stage lymphoblastic lymphoma with

● Adult T-cell lymphoma/leukemia, diffuse large B-cell lymphoma, peripheral T-cell

Intermediate risk — The intermediate-risk group (risk of TLS 1 to 5 percent) includes [16]:

● Adult T-cell lymphoma/leukemia, diffuse large B-cell lymphoma, peripheral T-cell

● Adult T-cell lymphoma/leukemia, diffuse large B-cell lymphoma, peripheral T-cell

● CLL/small lymphocytic lymphoma (SLL) treated with fludarabine, rituximab, or

● Multiple myeloma and chronic myelogenous leukemia (CML)

● Other solid tumors

We generally recommend hydration but do not administer any form of prophylactic

Risk stratification in acute leukemia — Predictive models for the probability of TLS in

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS

● Pathogenesis, clinical manifestations, and definition

• Tumor lysis syndrome (TLS) is an oncologic emergency that is caused by massive

- Laboratory TLS is defined as any two or more of the following metabolic

instituting chemotherapy: hyperuricemia, hyperkalemia, hyperphosphatemia,

● Etiology and risk factors

• TLS is observed most frequently in patients with high-grade lymphomas (particularly

● Risk stratification – Risk stratification based upon tumor-related and patient-related

Use of UpToDate is subject to the Terms of Use.

alkalinisation. Ann Oncol 2004; 15:175.

6-14_QuickReference_5x7.pdf (Accessed on April 27, 2011).

Am J Hematol 2003; 72:212.

Pediatr Hematol Oncol 2008; 30:267.

lymphocytic leukemia. J Clin Oncol 2008; 26:2519.

70. Esparza S, Muluneh B, Galeotti J, et al. Venetoclax-induced tumour lysis syndrome in

Endogenous production of uric acid

Endogenous production of uric acid

Excessive purine catabolism results in the production of

XO: xanthine oxidase; UO: urate oxidase.

Graphic 79178 Version 3.0

Uric acid crystals in the urine

Courtesy Gary C Curhan, MD, ScD.

Graphic 61827 Version 5.0

Cairo-Bishop definition of laboratory tumor lysis syndrome

Element Value Change from baseline

Uric acid ≥476 micromol/L (8 mg/dL) 25% increase

Potassium ≥6.0 mmol/L (or 6 mEq/L) 25% increase

Phosphorus ≥2.1 mmol/L (6.5 mg/dL) for children or 25% increase