• Plasma uric acid concentration measured by the area under the curve (AUC) at baseline through 48 hours after the last dose of chemotherapy
  
• Safety profile as measured by laboratory tests and adverse events at baseline through day 35
  

• Immune response to rasburicase as measured by plasma immunoassay (IgG, IgE, and neutralizing antibody) at baseline through 6 months after treatment or until negative after 6 months
  
• Pharmacokinetics of rasburicase as measured by plasma levels at baseline through day 14
  

OBJECTIVES:

Primary

• Determine response in patients with relapsed or refractory lymphoma, leukemia, or malignancy previously treated or not treated with rasburicase as treatment or prevention of hyperuricemia and tumor lysis syndrome.
• Determine response to this drug in these patients.

Secondary

• Determine the safety of this drug in these patients.
• Determine the plasma uric acid AUC in patients treated with this drug.
• Determine the incidence, duration, and type of immune responses (immunoglobulin [Ig] G, IgE, and neutralizing antibody) in patients treated with this drug.
• Determine the efficacy and safety of this drug, in relation to antibody generation and titer, in these patients.

OUTLINE: This is an open-label, multicenter study. Patients are stratified according to prior treatment with a uricolytic agent (yes vs no).

Patients receive rasburicase IV over 30 minutes on days 1-5 (or days 1-7). Treatment continues in the absence of unacceptable toxicity.

Patients receive cytoreductive chemotherapy off-study beginning 4-24 hours after the first dose of rasburicase.

Patients are followed at 14 days after the first dose of study treatment. After completion of study treatment, patients are followed at 30 days, at 3 and 6 months, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 170 patients (85 per stratum) will be accrued for this study within 18 months.

DISEASE CHARACTERISTICS:

• Meets 1 of the following risk criteria for tumor lysis syndrome:

  • At high-risk, with any of the following diagnoses:

    • Hyperuricemia of malignancy (plasma uric acid > 7.5 mg/dL)
    • Very aggressive lymphoma or leukemia in first relapse
    • Acute myeloid leukemia
    • Chronic myelogenous leukemia in blast crisis

    • One of the following high-grade myelodysplastic syndromes AND ≥ 10% bone marrow blasts AND are undergoing aggressive chemotherapy:

      • Refractory anemia with excess blasts [RAEB]
      • RAEB in transformation
      • Chronic myelomonocytic leukemia

  • At potential-risk AND a diagnosis of an aggressive lymphoma or leukemia AND meets at least 1 of the following criteria:

    • Lactic dehydrogenase ≥ 2 times upper limit of normal
    • Stage III or IV disease
    • Stage I or II disease with 1 lymph node or tumor > 5 cm in diameter
• First relapse or refractory disease

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• ECOG 0-3

Life expectancy

• More than 3 months

Hematopoietic

• No history of hemolysis indicative of G6PD deficiency

Hepatic

• See Disease Characteristics

Renal

• Not specified

Pulmonary

• No established diagnosis of asthma

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 30 days after study participation
• No severe, life-threatening atopic allergy
• No hypersensitivity to uricases or their excipients
• No known G6PD deficiency

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 12 months since prior rituximab
• No concurrent rituximab

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No concurrent urine alkalinization
• No other concurrent allopurinol
• No other concurrent uricolytic agents
• No other concurrent investigational drug