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878 PART 7: Hematologic and Oncologic Disorders

Laboratory tumor lysis syndrome
Uric acid 8 mg/dL ( 476 mol/L) or 25% increase from baseline
Potassium 6 mEq/L ( 6 mmol/L) or 25% increase from baseline
Phosphorus 4.5 mg/dL ( 2.1 mmol/L) or 25% increase from baseline

Calcium 7 mg/dL ( 1.75 mmol/L) or 25% decrease from baseline
Clinical tumor lysis syndrome
Serum creatinine 1.5 times the upper limit of normal
Cardiac arrhythmia or sudden death
Seizure

FIGURE 93-3. Cairo-Bishop diagnostic criteria for tumor lysis syndrome. (Adapted with permission from from Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and
classification. Br J Haematol. October 2004;127(1):3-11, with permission from Blackwell Publishing Group.)

levels are necessary on days prior and after cytoreduction. Earlier that the rasburicase is more effective in reducing uric acid levels and
guidelines recommended alkalinization of urine with sodium bicar- preventing renal failure. 110,111 Adverse effects reported with rasburicase
bonate to make uric acid more soluble and prevent its precipitation include hypersensitivity, methemoglobinemia, and hemolysis in patients
in the renal tubules. However, an alkalotic urinary pH has been with glucose-6-phosphate dehydrogenase deficiency. 101,102 Rasburicase
105
shown to increase phosphate and xanthine precipitation in the renal is considerably more expensive than allopurinol. As a result, different
tubules. 65,100,106 Thus, current guidelines no longer recommend adminis- studies have evaluated the efficacy of smaller single doses of rasburicase,
tration of sodium bicarbonate. 100,106 Diuretics can be used for decreased or limiting its use to cases with particularly elevated uric acid levels. 65,112
urine output but their use has not been associated to improve outcomes. The use of rasburicase at a dose of 0.1 to 0.2 mg/kg via iv infusion over
101
Indications for hemodialysis in TLS include signs of uremia, volume over- 30 minutes once daily for 5 days is recommended in patients who are at
load, persistent hyperkalemia, and acidosis. It is also recommended that high risk for TLS. 100
patients with severe hyperphosphatemia and symptomatic hypocalcemia Current guidelines on management of TLS are based on the risks and
be initiated on hemodialysis. 100,107 Prophylactic or early hemodialysis, severity of the syndrome (Fig. 93-4). 100,108 While there are no studies
however, has not been studied for TLS. 108 comparing outcomes of these different guidelines, they all facilitate
Allopurinol, a xanthine oxidase inhibitor that blocks production of early recognition of high-risk patients and initiation of early aggressive
109
uric acid, has been used since the early 1960s for TLS. Allopurinol treatment.
should be started 48 hours prior to initiation of cytotoxic treatment
in patients at risk for TLS, and can be administered both orally and LEUKOSTASIS
intravenously with the same effectiveness. 101,102 While allopurinol is
3
effective in preventing uric acid production, it does not have any effect Hematologic malignancies with hyperleukocytosis (>100,000/mm )
in those with preexisting hyperuricemia. Moreover, production of xan- may develop leukostasis when blasts aggregate in the microvascula-
thine, which can also precipitate in the renal tubules, is not inhibited ture and cause organ dysfunction. 113,114 Leukostasis is more common
by allopurinol. In contrast, rasburicase, a recombinant urate oxidase, in acute leukemias with an incidence of 10% to 30% in patients with
100
degrades already formed uric acid into allantoin which is easily excreted acute myelogenous leukemia (AML) and acute lymphoblastic leukemia
in urine. Studies comparing rasburicase to allopurinol have shown (ALL). Its presence is associated with a high recurrence of disease
113
110
Type of cancer Low risk Intermediate risk High risk
NHL Indolent NHL DLBCL Burkitt, lymphoblastic, Burkitt
ALL
ALL WBC <50,000/mm 3 WBC 50,000-100,000/mm 3 WBC >100,000/mm 3
3
AML WBC <10,000/mm 3 WBC 10,000-50,000/mm 3 WBC >50,000/mm ; monoblastic
3
CLL WBC <10,000/mm 3 WBC 10,000-100,000/mm ;
fludarabine treatment
Others a Remainder of patients Rapid proliferation with
expected rapid response

Treatment Clinical judgment and monitoring Hydration and allopurinol; Hydration and rasburicase
rasburicase if hyperuricemia
develops
a All other hematological malignancies including CML and MM, and solid tumors.
FIGURE 93-4. Risk stratification and treatment for tumor lysis syndrome. ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CLL, chronic lymphocytic leukemia; CML, chronic
myeloid leukemia; DLBCL, diffuse large B-cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma. (Adapted with permission from Coiffier B, et al. Guidelines for the management
of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol. June 1, 2008;26(16):2767-2778, with permission from the American Society of Clinical Oncology.)

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