Pitfalls, prevention, and treatment of hyperuricemia during tumor lysis syndrome in the era of rasburicase (recombinant urate oxidase)

Figures & data

Table 1 Laboratory criteria of tumor lysis syndrome

Uric acid	Increase of more than 25% from baseline if available or Values ≥476 μmol/L 8 mg/dL
Potassium	Increase of more than 25% from baseline if available or Values ≥6.0 mmol/L 6 mEq/dL
Phosphorus	Increase of more than 25% from baseline if available or Values ≥1.45 mmol/L 4.5 mg/dL for adults patients Values ≥2.1 mmol/L 6.5 mg/dL for pediatric patients
Calcium	Decrease of more than 25% from baseline if available or Values ≥1.75 mmol/L 7 mg/dL

Modified from Cairo and Bishop (2004).

Table 2 Risk stratification definition and criteria

At high risk of developing tumor lysis syndrome are those patients who carry at least one of the following co-morbidities, disease-related or therapy-related factors
	Pediatric patients
Co-morbidities	- Renal impairment at diagnosis appear to be the only relevant co-morbidity in children - Kidney tumor involvement at onset - Hyperuricemia UA > 8 mg/dL
Disease-related factors	- Tumors with high proliferative rate - Bulky solid tumor especially if massive liver metastasis - Lympho-myeloproliferative disorders with large tumor burden as WBC > 50,000/mm^3 or LDH > 2 times normal level - High grade lymphomas particularly Burkitt’s lymphoma and T-cell NHL - B-cell and T-cell acute lymphoblastic leukemias
Treatment-related factors	- Intensive cytoreductive chemotherapy in hematologic malignancies
	Adult patients
Co-morbidities	- Dehydratation - Hyponatriemia - Pre-existing renal impairment including tumor infiltration that reduce renal function - Obstructive uropathy - Hyperuricemia UA > 10 mg/dL
Disease-related factors	- Tumors with high proliferative rate - Bulky solid tumor especially if massive liver metastasis - Lympho-myeloproliferative disorders with large tumor burden such as > 50,000/mm^3 or LDH > 2 times normal level - Advanced germ cell lung cancer - High grade lymphomas particularly Burkitt’s lymphoma, a T-cell NHL - B-cell acute lymphoblastic leukemias
Treatment-related factors	- Intensive cytoreductive chemotherapy in hematologic malignancies

Abbreviations: LDH, lactate dehydrogenase; NHL, non-Hodgkin lymphoma; UA, uric acid; WBC, white blood cell.

Figure 1 Purine catabolic pathway and site of action of allopurinol and rasburicase.

Figure 2 Pathogenesis of tumor lysis syndrome.

Table 3 Prevention of tumor lysis syndrome

	Pediatric patients
Low risk	- Allopurinol orally 300 mg/m^2/day or 10 mg/kg/day 3 times. - However a single dose of rasburicase will be take into account for also low-risk patients - Hyperhydratation with glucosaline or normal saline solution 2.5–3 L/m^2/day or 200 mL/kg/day if children <10 kg - Alkalinization NaHCO3 50–70 mEq/L to maintain urinary pH > 7 - Furosemide if urine volume is < 100 mL/m^2/h or 3mL/kg/h for children <10 kg
High risk	- Rasburicase 0.2 mg/kg/day at least 4 hours before beginning chemotherapy for 3–5 days - Hyperhydratation with glucosaline or normal saline solution 2.5–3 L/m^2/day or 200 mL/kg/day if children <10 kg - Furosemide if urine volume is <100 mL/m^2/h or 3 mL/kg/h for children <10 kg
	Adult patients
Low risk	- Allopurinol orally 300 mg/m^2/day 3 times - Hyperhydratation 2.5–3 L/m^2/day with glucosaline or normal saline solution. Hydratation should always be performed, except in patients at risk of rapid volume overload - Alkalinization to maintain urine pH > 7 - Furosemide or mannitol if urine volume is <100 mL/m^2/h. Diuretics should be administered unless hypovolemia or obstructive uropathy are diagnosed to maintain urine outputof at least 100 mL/m^2/h with urinary specific gravity ≤1010
High risk	- Rasburicase 0.05–0.2 mg/kg/day for 3–5 days - Hyperhydratation 2.5–3 L/m^2/day with glucosaline or normal saline solution. Hydratation should always be performed, except in patients at risk of rapid volume overload - Furosemide or mannitol if urine volume is <100 mL/m^2/h. Diuretics should be administered unless hypovolemia or obstructive uropathy are diagnosed to maintain urine output of at least 100 mL/m^2/h with urinary specific gravity ≤1010 - For solid tumors reduced chemotherapy schedule may be evaluated to reduce tumor burden and related TLS risk

Rasburicase is contraindicated in patients with metahemoglobinemia, G6PD deficiency or other metabolic disorders that may cause hemolitic anemia.

Table 4 Treatment of laboratory tumor lysis syndrome (LTLS and clinical tumor lysis syndrome (CTLS)

	Laboratory TLS pediatric patients
Low risk	- Allopurinol orally 300 mg/m^2/day or 10 mg/kg/day 3 times. - However a single dose of rasburicase will be take into account for also low-risk patients - Hyperhydratation with glucosaline or normal saline solution 2.5–3 L/m^2/day or 200 mL/kg/day if children <10 kg - Urine alkalinization NaHCO3 50–70 mEq/L to maintain urinary pH > 7 - Furosemide if urine volume is <100 mL/m^2/h or 3 mL/kg/h for children <10 kg
High risk	- Rasburicase 0.2 mg/kg/day. at least 4 hours before beginning chemotherapy for 3–5 days - Hyperhydratation with glucosaline or normal saline solution 2.5–3 L/m^2/day or 200 mL/kg/day if children <10 kg - Furosemide if urine volume is <100 mL/m^2/h or 3 mL/kg/h for children <10 kg
Clinical TLS pediatric patients
- Rasburicase 0.2 mg/kg/day at least 4 hours before beginning chemotherapy for 3–5 days. - Hyperhydratation with glucosaline or normal saline solution 2.5–3 L/m^2/day or 200 mL/kg/day if children <10 kg. - Furosemide if urine volume is <100 mL/m^2/h or 3 mL/kg/h for children <10 kg. - Consider hemodialysis.
Laboratory and clinical TLS adult patients
There is no major differences in treatment of laboratory and clinical TLS in adult patients
- Rasburicase 0.2 mg/kg/day for 3–5 days. - Hyperhydratation 2.5–3 L/m^2/day with glucosaline or normal saline solution. Hydratation should always be performed, except in patients at risk of rapid volume overload. - Furosemide or mannitol if urine volume is <100 mL/m^2/h. Diuretics should be administered unless hypovolemia or obstructive uropathy are diagnosed to maintain urine output of at least 100 mL/m^2/h with urinary specific gravity ≤1010. - Low dose dopamine can be used to improve renal perfusion. - Consider hemodialysis.

Rasburicase is contraindicated in patients with metahemoglobinemia, G6PD deficiency or other metabolic disorders that may cause hemolitic anemia.

CairoMSBishopM2004Tumour lysis syndrome: new therapeutic strategies and classificationBr J Haematol12731115384972

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