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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Standard therapy in the United States for malignancy-associated
hyperuricemia consists of hydration, alkalinization, and allopurinol. Urate oxidase catalyzes the enzymatic oxidation of uric acid to a 5 times increased urine soluble product, allantoin. Rasburicase is a new
recombinant form of urate oxidase available for clinical evaluation.
This multicenter randomized trial compared allopurinol to rasburicase
in pediatric patients with leukemia or lymphoma at high risk for tumor
lysis. Patients received the assigned uric acid-lowering agent for 5 to
7 days during induction chemotherapy. The primary efficacy end point
was to compare the area under the serial plasma uric acid concentration
curves during the first 96 hours of therapy (AUC0-96).
Fifty-two patients were randomized at 6 sites. In an intent-to-treat
analysis, the mean uric acid AUC0-96 was 128 ± 70
mg/dL.hour for the rasburicase group and 329 ± 129 mg/dL.hour for
the allopurinol group (P < .0001). The rasburicase versus allopurinol group experienced a 2.6-fold (95% CI:
2.0-3.4) less exposure to uric acid. Four hours after the first dose,
patients randomized to rasburicase compared to allopurinol achieved an
86% versus 12% reduction (P < .0001) of initial plasma uric acid levels. No antirasburicase antibodies were detected at day
14. This randomized study demonstrated more rapid control and lower
levels of plasma uric acid in patients at high risk for tumor lysis who
received rasburicase compared to allopurinol. For pediatric patients
with advanced stage lymphoma or high tumor burden leukemia, rasburicase
is a safe and effective alternative to allopurinol during initial chemotherapy.
(Blood. 2001;97:2998-3003) In patients with myeloproliferative diseases or
hematopoietic malignancies, nucleic acids are catabolized as a result
of increased turnover of malignant cell populations. This results in an
increase in purine metabolism, leading to hyperuricemia. Aggressive
cancer chemotherapy regimens cause an increase in cell lysis and
release of purine metabolites.1 Tumor lysis syndrome is
characterized by severe hyperuricemia, hyperphosphatemia, hyperkalemia,
hypocalcemia, and acute renal failure.2-6 As a consequence
of hyperuricemia, renal insufficiency develops when urine becomes
supersaturated with uric acid and crystals of uric acid form in the
renal tubules and distal collecting system.2,7 Moreover,
despite management of metabolic abnormalities to reduce the risk of
acute renal failure, 25% of children with advanced-stage Burkitt
lymphoma and B-cell acute lymphoblastic leukemia still experience acute
renal failure at onset of cytoreductive
chemotherapy.8-10
The standard treatment for hyperuricemia in the United States consists
of allopurinol, urinary alkalinization, and hydration.11 By inhibiting the enzyme xanthine oxidase, allopurinol blocks uric acid
formation (Figure 1). This increases the
plasma concentrations of the uric acid precursors hypoxanthine and
xanthine.11 Patients at high risk for tumor lysis still
need to excrete preexisting uric acid, which is not affected by
allopurinol treatment. Consequently, a drug that has rapid and highly
potent uricolytic properties, reduces metabolic morbidity, and can be
conveniently integrated with the initiation of a cancer chemotherapy
regimen would be helpful in the supportive management of this patient
population.
Urate oxidase catalyzes the enzymatic oxidation of uric acid into
allantoin (Figure 1), a readily excretable substance about 5 times more
soluble than uric acid.12 Urate oxidase is an endogenous enzyme found in most mammals, but not in humans because of a nonsense mutation in the coding region in the gene during hominoid
evolution.13 Rasburicase is a recombinant form of
the urate oxidase enzyme.14 A study in healthy adult male
volunteers established that single daily intravenous doses of
rasburicase were well tolerated and led to dramatic decreases in plasma
uric acid levels.15 A recent multicenter phase II trial of
rasburicase in pediatric patients with leukemia and lymphoma
(n = 131) demonstrated that 100% of patients achieved uric acid
control at a dose of rasburicase of 0.2 mg/kg despite concomitant
intensive chemotherapy.16 The present study reports the
efficacy of rasburicase compared to allopurinol in reducing exposure to
plasma uric acid in children with leukemia or lymphoma at high risk for
developing tumor lysis syndrome.
Study design
Eligibility criteria
Exclusion criteria included patients with previous treatment with rasburicase or Uricozyme, treatment with allopurinol within 7 days, and a significant history of documented asthma, atopy, or deficiency of glucose-6-phosphate dehydrogenase (G6PD). Randomization and treatment Via telephone entry, treatment (rasburicase or allopurinol) was randomly allocated to patients according to a computer-generated randomization code schema. Randomization was stratified according to presentation uric acid (< 8.0 mg/dL or 8.0 mg/dL) and disease (leukemia or lymphoma).
Patients were scheduled to receive 5 to 7 days of either uric acid-lowering agent (rasburicase or allopurinol). The dose and schedule of rasburicase was 0.20 mg/kg intravenously given over 30 minutes daily.16 Oral allopurinol therapy was dosed by the individual investigators according to the package insert and standard clinical practice. Standard pediatric allopurinol dosing was 300 mg/m2 (or 10 mg/kg) divided every 8 hours. Intravenous sodium bicarbonate (generally with 20-40 mEq/L fluid) to increase urine alkalinization was permitted at the investigators' discretion. All patients, regardless of treatment group, received hydration (~ 3 L/m2 daily). The study duration was to be 14 days for each patient, including 5 to 7 days of treatment and a final safety assessment on day 14. Outcome measurements and follow-up All study patients had detailed analysis of plasma uric acid values during the first 96 hours of uric acid-lowering agent therapy. Plasma uric acid was measured at the clinical laboratories of the participating institutions. Special handling procedures and strict temperature conditions (0°C-4°C) were observed during the blood collection procedures to block ex vivo enzymatic activity of rasburicase. These temperature conditions were previously shown to result in less than 3.4% ex vivo degradation for up to 4 hours after blood withdrawal (data not shown). Plasma uric acid levels were measured immediately before administration of uric acid-lowering agents (T0h) and at hours 4 and 12, and then every 12 hours through 96 hours. Complete physical examinations and symptom and toxicity assessments were performed at least daily while the children were hospitalized. Complete blood counts with differential and serum chemistries were performed as required by the patients' chemotherapy protocols or as clinically appropriate. In addition, antibody to urate oxidase protein was determined in patients receiving rasburicase on day 0 and day 14 of the study. After treatment, detailed physical examination, plasma uric acid, complete blood counts, serum chemistries, and urinalysis were required on day 8 of study or 24 to 48 hours after completion of uric acid- lowering therapy (whichever occurred first). On day 14 a symptom/toxicity assessment was performed.The main objective of the study was to compare the decrease in plasma uric acid levels by the 2 uric acid-lowering agents during the first 5 days of cytoreductive chemotherapy. The primary efficacy end point was the area under the serial plasma uric acid concentration curves from the start of study drug until 96 hours (AUC0-96). The AUC0-96 was constructed for all patients and across treatment groups as well as subgroups of interest. Last value carried forward method was used to estimate the missing data for patients who discontinued the study prematurely and linear interpolation method was used to impute the missing data between visits. Hyperuricemic patients were defined as patients with a plasma uric acid value of 8 mg/dL or above either at presentation or hour 0 (ie, immediately before first dose of study drug administration). A secondary end point was the percent reduction of uric acid at 4 hours after first dose of uric acid-lowering agent therapy (ie, prior to induction chemotherapy). Safety and toxicity Safety analyses were performed in all patients and compared between treatment groups. All adverse events were coded according to the World Health Organization Adverse Reactions Terminology (WHO-ART) and assigned a system-organ class. Antirasburicase antibody determination was performed under the responsibility of Sanofi Research Division, Great Valley, PA via an enzyme-linked immunosorbent assay (ELISA) technique as previously reported.18Statistical analysis The primary efficacy end point was the plasma uric acid AUC0-96. The end point was computed for each patient using the trapezoidal rule. Linear interpolation was used to compute a missing value. Values collected below the limit of quantification (LOQ) were replaced by the LOQ value. Descriptive summary statistics (N, mean, median, SD) were computed for each treatment group. A one-way analysis of variance (ANOVA) model was used to evaluate the treatment effect on plasma uric acid AUC0-96 and percent change from baseline plasma uric acid concentrations at 4 hours. Subgroup analyses were similarly performed by disease (lymphoma or leukemia) or presenting uric acid values (< 8 mg/dL or 8 mg/dL). Descriptive statistics and statistical analyses of the safety and efficacy data
were calculated using SAS software, Version 6.12 on a Sanofi Alphaserver.
Patients Fifty-two patients were randomized at 6 sites within the United States between November 1996 and December 1997. Patient baseline demographics and disease type are shown in Table 1. There were no statistical differences in the age, race, male/female ratios, or performance status for patients randomized to rasburicase versus allopurinol. The mean age for patients assigned rasburicase versus allopurinol was 7.1 years versus 7.8 years, respectively. Eighty-nine percent of patients assigned to rasburicase had ECOG scores of one or less compared to 84% assigned to allopurinol. Twenty patients with leukemia received rasburicase and 19 patients received allopurinol. Seven patients with lymphoma received rasburicase versus 6 receiving allopurinol. A similar number of patients with advanced Burkitt leukemia/lymphoma (mature B-cell leukemia or stage III Burkitt small noncleaved-cell lymphoma)
were in each treatment group (5 rasburicase, 4 allopurinol). In
addition, there was no significant differences in initial tumor burden
markers between treatment arms (ie, WBC count in the leukemia patients
and lactic dehydrogenase [LDH] in the lymphoma patients). Patient
randomizations were also stratified according to presenting uric acid
values. Despite this, mean presenting uric acid values were higher in
patients assigned rasburicase by about 1 mg/dL, but this did not reach
statistical significance. Rasburicase patients presented with a mean
uric acid value ± SD of 7.7 ± 3.5 mg/dL versus 6.8 ± 3.4
mg/dL in allopurinol patients. All other metabolic parameters were
similar between treatment groups including calcium, potassium, and
phosphorus. Finally, the presentation creatinine levels were nearly
identical between groups, with the rasburicase patients presenting with a mean creatinine of 0.60 ± 0.33 mg/dL versus 0.61 ± 0.30 mg/dL in allopurinol patients (Table 1).
Drug administration All 52 patients randomized received at least one dose of their assigned treatments with rasburicase or allopurinol. Patients assigned rasburicase received a dose once every 24 hours, except for one patient with early pre-B cell ALL with a WBC count of 178 × 109/L and a uric acid value of 4.1 mg/dL who received every 12-hour dose × 4 because of investigator preference. A total of 387 doses (median number of 3 doses/d) of oral allopurinol were administered with a median dose of 100 mg (1 tablet) per dose. The mean time from study drug administration to start of chemotherapy (excluding intrathecal therapy) was 21 hours in both treatment groups. The treatment protocol was violated in 2 patients in each arm because chemotherapy was started prior to the initiation of the study drug. Four patients withdrew from the study before completion of randomized drug. One patient assigned to rasburicase withdrew after 4 doses because of grade 4 hemolysis; a relationship to the study drug was not known by the investigator (see "Adverse events and mortality"). Three patients assigned to allopurinol withdrew from study prior to completion. Two of these patients suffered unrelated deaths (see below) during induction chemotherapy after 14 and 8 doses of allopurinol, respectively. The third patient was withdrawn after 14 doses of allopurinol because chemotherapy had not been administered. All patient data were used regardless of study completion in an intent-to-treat analysis.Control of plasma uric acid The primary end point of this trial was the control of uric acid through the first 96 hours of therapy with concomitant induction chemotherapy appropriate for the specific disease. Patients treated with rasburicase had a more rapid decline and maintained lower plasma uric acid levels throughout induction chemotherapy (Figure 2). The area under the curve for mean uric acid AUC0-96 was used to quantify the exposure to uric acid during the first 96 hours of induction chemotherapy (Figure 2). In an intent-to-treat analysis, the mean AUC0-96 was 128 ± 70 mg/dL.hr for the rasburicase group and 329 ± 129 mg/dL.hr for the allopurinol group (P < .0001). Patients receiving rasburicase on average experienced a 2.6-fold less exposure to uric acid during the first 96 hours of therapy. For the subgroup of 19 hyperuricemic patients any time prior to dosing, there was a similar reduction in uric acid exposure during therapy in patients who received rasburicase (Table 2). Although no attempt was made to randomize the small number of patients with Burkitt lymphoma in this trial, these patients are at greatest risk for hyperuricemic nephropathy during initiation of treatment.9,10 As illustrated in Table 2, patients with advanced Burkitt lymphoma had the greatest reduction in exposure to uric acid (~ 4-fold) when comparing rasburicase treatment to allopurinol during the first 96 hours of therapy. Thus, the advantageous decrease in uric acid was evident across all patients included in the study as well as in treatment subgroups, normouricemic versus hyperuricemic patients, and patients with leukemia or lymphoma.
The rapidity of control of uric acid by study drug was a secondary end
point in this trial. We found a striking difference between the single
dose of intravenous rasburicase at 0.20 mg/kg versus standard doses of
oral allopurinol. For patients randomized to rasburicase, there was an
86% reduction in plasma uric acid levels after 4 hours of the first
dose compared to only 12% for allopurinol (P < .0001).
Finally, we examined the fall in plasma uric acid in patients who were
hyperuricemic (uric acid > 8 mg/dL at T = 0). Patients
hyperuricemic at baseline and treated with rasburicase (n = 10) all
achieved a uric acid concentration of less than 8 mg/dL in less than 4 hours. In contrast, no patients hyperuricemic at start of allopurinol
(n = 5) achieved a uric acid level less than 8 mg/dL by 4 hours
(Figure 3).
Renal outcome The study sample size was too small to determine a difference in the incidence of renal failure or required renal support. One patient who received allopurinol required hemodialysis during the study period. This patient was a 12-year-old with stage IV Burkitt lymphoma who had renal failure, hypocalcemia, and a maximum serum phosphorous of 20.2 mg/dL on day 2 of standard cytoreductive chemotherapy with cyclophosphamide, vincristine, and prednisone. He underwent hemodialysis followed by hemofiltration for 6 days with recovery of renal function. In contrast, a 15-year-old girl with a bulky presentation of pre-B ALL in the rasburicase group presented with frank renal insufficiency with a creatinine of 2.5 mg/dL at baseline and a uric acid concentration of 16.5 mg/dL. This patient's renal function improved during therapy without the need for any type of dialysis or hemofiltration.To more closely examine the relationship of renal function to treatment
arm, we studied creatinine levels over the first 96 hours of therapy
for the hyperuricemic patients. Panels A and B in Figure
4 show the actual creatinine values for
hyperuricemic patients by study drug received. From infancy through
adolescence, "normal" serum creatinine levels can vary greatly
(~3-fold) by age and sex.20 We therefore adjusted each
patient's creatinine level by expressing it as a percentage of the
published mean for age and gender to facilitate comparison in the
hyperuricemic patients by study drug (Figure 4C). The hyperuricemic
patients who received rasburicase had a baseline creatinine of
144% of their age/sex-defined mean. A steady decline occurred through
the 4 days of therapy to an adjusted creatinine level of 102%. In
contrast, the hyperuricemic allopurinol group had a baseline creatinine
of 132%, which worsened over the 4 days of therapy to 147% of mean
(Figure 4C).
Adverse events and mortality Frequent adverse events were common among the study patients including fever, pain, and mucositis secondary to their disease and chemotherapeutic regimens. Two patients assigned allopurinol died during the study period. A 6-year-old girl with T-cell leukemia died of pseudomonal sepsis on day 11 of study, and a 2-year-old girl with acute myelogenous leukemia died of an intracerebral hemorrhage on day 2 of study. Therapy was discontinued for one patient receiving rasburicase because of hemolysis. This 11-year-old boy with pre-B precursor ALL had evidence of disseminated intravascular coagulopathy, which resolved concomitantly with discontinuation of the rasburicase; the relationship to rasburicase is unknown. Testing of the patient's blood and the 6 red blood cell donors from whom he received transfusions did not show any evidence of underlying G-6-PD deficiency. No patients experienced anaphylactic events due to rasburicase. Predose and end-of-study samples for the qualitative determination of antibodies to urate oxidase protein were received from 23 of 27 patients assigned rasburicase. None of the samples contained detectable amounts of antibodies to rasburicase.
The use of urate oxidase is not a new therapeutic modality for the treatment of hyperuricemia associated with hematologic malignancies.21,22 The aspergillus-derived protein (nonrecombinant urate oxidase, Uricozyme) has been used in France and Italy for almost 3 decades. A report from France using the nonrecombinant urate oxidase protein in children with advanced Burkitt lymphoma/mature B-cell ALL demonstrated only a 1.7% incidence of dialysis during induction chemotherapy.23 This compares favorably to a recent report in the United States in which 21% of children with advanced Burkitt lymphoma treated with allopurinol, hydration, and alkalinization required hemodialysis during induction chemotherapy and 6 patients died during induction therapy secondary to renal/metabolic complications.10 Pui and colleagues treated 134 children with acute leukemia and Burkitt lymphoma with the nonrecombinant urate oxidase.24 They found a more rapid and significantly greater decrease in blood uric acid levels than historical controls treated with similar chemotherapy and allopurinol. However, 4.5% of the children given aspergillus-purified urate oxidase developed allergic reactions, manifested primarily by urticaria, bronchospasm, and hypoxia.24 The present study is the first randomized comparison of recombinant urate oxidase (rasburicase) versus allopurinol in pediatric patients with hematologic malignancies at high risk for tumor lysis. In the present study, mean uric acid AUC0-96 was
statistically significantly lower in the rasburicase group (128.1 mg/dL.hr) than in the allopurinol group (328.5 mg/dL.hr, P < .0001). Mean percent change from
baseline uric acid concentration was Moreover, the incidence of renal failure requiring assisted renal support (dialysis or hemofiltration) during this study was null in the rasburicase group compared to one patient in the allopurinol group. This patient had a plasma creatinine level within normal range at baseline and developed renal failure secondary to tumor lysis syndrome during allopurinol dosing. In contrast, one patient in the rasburicase group, with a serum creatinine level of 2.2 mg/dL, improved without assisted renal support. Hyperuricemic patients who received rasburicase improved their adjusted creatinine levels from 144% to 102% of mean for age and gender, from baseline through day 4 of study, respectively. In contrast, hyperuricemic patients who received allopurinol had worsening adjusted creatinine levels from 132% to 147% of mean, from baseline through day 4 of study (P = .147 comparing change from baseline through day 4 by treatment group). This corresponds to a period where cytoreductive chemotherapy had begun and suggests that the more rapid control of plasma uric acid may have translated into superior renal function during chemotherapy for patients treated with rasburicase. The study was not designed to compare renal function outcome, the incidence of renal failure, or the need for assisted renal support between the 2 treatment arms. Therefore, the number of hyperuricemic patients may have been too small to demonstrate any statistically significant differences. In summary, this study supports the conclusion that rasburicase is a safe and effective alternative to allopurinol to rapidly control plasma uric acid concentrations in patients with hematologic malignancies at high risk for tumor lysis during induction/reduction chemotherapy. A larger number of patients would be required to determine if the more rapid control and reduction of plasma uric acid with rasburicase will also result in a significant decrease in metabolic complications and morbidity due to tumor lysis syndrome, or the need for additional renal support (dialysis or hemofiltration).
We are indebted to the support of Vicki Toan and Linda Rahl for the editorial assistance in the preparation of this manuscript. We would also like to thank Francine High and James Grabicki from Sanofi-Synthelabo for their assistance in the study and helpful comments regarding the manuscript.
Department of Pediatric Hematology/Oncology at North Texas Hospital for Children at Medical City, Dallas, TX; Department of Pediatric Hematology/Oncology at Children's Hospital and Medical Center, Seattle, WA; Jonathan Jaques Children's Cancer Center at Miller Children's Hospital, Long Beach, CA; Department of Pediatrics at Mott Children's Hospital, Ann Arbor, MI; Department of Pediatric Hematology/Oncology at Riley Hospital for Children, Indianapolis, IN; Department of Pediatric Hematology/Oncology at Doernbecher Children's Hospital, Portland, OR; Sanof-Synthelabo, Inc, Malvern, PA; and the Department of Pediatrics at the Babies and Children's Hospital, Columbia University, New York, NY.
Submitted September 25, 2000; accepted January 23, 2001.
Supported by a grant from Sanofi-Synthelabo, Malvern, PA.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Presented in part at the American Society of Hematology Conference in Miami Beach, FL, December 1998. Reprints: Mitchell S. Cairo, Blood and Marrow Transplantation, Pediatric Cancer Research, Babies and Children's Hospital, Columbia University, 161 Fort Washington Ave, Irving 7, New York, NY 10032; e-mail: mc1310{at}columbia.edu.
1. Hande KR. Hyperuricemia, uric acid nephropathy, and the tumor lysis syndrome. In: McKinney TD, ed. Renal Complications of Neoplasia. New York, NY: Praeger; 1986:134-156. 2. Arrambide K, Toto RD. Tumor lysis syndrome. Semin Nephrol. 1993;13:273-280[Medline] [Order article via Infotrieve]. 3. Wibe E, Kvaloy S, Nome O, Abrahamsen AF, Bjorgo S. Tumor lysis syndrome. A life-threatening complication during cytostatic treatment of chemosensitive types of cancer. Tidsskr Nor Laegeforen. 1991;111:2435-2437[Medline] [Order article via Infotrieve]. 4. Jones DP, Stapleton FB, Kalwinsky D, McKay CP, Kellie SJ, Pui CH. Renal dysfunction and hyperuricemia at presentation and relapse of acute lymphoblastic leukemia. Med Pediatr Oncol. 1990;18:283-286[Medline] [Order article via Infotrieve]. 5. Stokes DN. The tumour lysis syndrome. Intensive care aspects of paediatric oncology. Anaesthesia. 1989;44:133-136[Medline] [Order article via Infotrieve]. 6. Andreoli SP, Clark JH, McGuire WA, Bergstein JM. Purine excretion during tumor lysis in children with acute lymphocytic leukemia receiving allopurinol: relationship to acute renal failure. J Pediatr. 1986;109:292-298[CrossRef][Medline] [Order article via Infotrieve]. 7. Pochedly C. Hyperuricemia in leukemia and lymphoma. Postgrad Med. 1974;55:93-99. 8. Cohen LF, Balow JE, Magrath IT, Poplack DG, Ziegler JL. Acute tumor lysis syndrome. A review of 37 patients with Burkitt's lymphoma. Am J Med. 1980;68:486-491[CrossRef][Medline] [Order article via Infotrieve].
9.
Stapleton FB, Strother DR, Roy Sd, Wyatt RJ, McKay CP, Murphy SB.
Acute renal failure at onset of therapy for advanced stage Burkitt lymphoma and B cell acute lymphoblastic lymphoma.
Pediatrics.
1988;82:863-869
10.
Bowman WP, Shuster JJ, Cook B, et al.
Improved survival for children with B-cell acute lymphoblastic leukemia and stage IV small noncleaved-cell lymphoma: a Pediatric Oncology Group study.
J Clin Oncol.
1996;14:1252-1261 11. DeConti RC, Calabresi P. Use of allopurinol for prevention and control of hyperuricemia in patients with neoplastic disease. N Engl J Med. 1966;274:481-486. 12. Brogard JM, Coumaros D, Franckhauser J, Stahl A, Stahl J. Enzymatic uricolysis: a study of the effect of a fungal urate-oxydase. Rev Eur Etud Clin Biol. 1972;17:890-895[Medline] [Order article via Infotrieve]. 13. Yeldandi AV, Yeldandi V, Kumar S, et al. Molecular evolution of the urate oxidase-encoding gene in hominoid primates: nonsense mutations. Gene. 1991;109:281-284[CrossRef][Medline] [Order article via Infotrieve].
14.
Legoux R, Delpech B, Dumont X, et al.
Cloning and expression in Escherichia coli of the gene encoding Aspergillus flavus urate oxidase.
J Biol Chem.
1992;267:8565-8570 15. Jacob F, Drelon E, Neefe J, Lascombes F. New drug to lower uric levels in healthy volunteers. Advances on prevention and control of hyperuricemia in malignancies [abstract]. Proc Annu Meet Am Assoc Cancer Res. 1996;37:1484a. 16. Pui C-H, Wiley JM, Woods GM, et al. Recombinant urate oxidase corrects hyperuricemia in patients treated for leukemia or lymphoma [abstract]. Blood. 1998;92:482a. 17. Murphy SB. Classification, staging and end results of treatment of childhood non- Hodgkin's lymphomas: dissimilarities from lymphomas in adults. Semin Oncol. 1980;7:332-339[Medline] [Order article via Infotrieve]. 18. Dussossoy D, Py ML, Pastor G, Boulenc X. Development of a two-site immunoassay of recombinant urate oxidase (SR 29142) and its use for determination of pharmacokinetic parameters in rats and baboons. J Pharm Sci. 1996;85:955-959[CrossRef][Medline] [Order article via Infotrieve]. 19. Finney DJ. Statistical Method in Biological Assay. 3rd ed. London, England: Charles Griffin; 1978:81-104. 20. Barone MA, ed. The Harriet Lane Handbook. 14th ed. St Louis: Mosby; 1996. 21. Masera G, Jankovic M, Zurlo MG, et al. Urate-oxidase prophylaxis of uric acid-induced renal damage in childhood leukemia. J Pediatr. 1982;100:152-155[CrossRef][Medline] [Order article via Infotrieve]. 22. Jankovic M, Zurlo MG, Rossi E, et al. Urate-oxidase as hypouricemic agent in a case of acute tumor lysis syndrome. Am J Pediatr Hematol Oncol. 1985;7:202-204[Medline] [Order article via Infotrieve]. 23. Patte C, Michon J, Bouffet E, et al. High survival rate of childhood B-cell lymphoma and leukemia (ALL) as result of the LMB 89 protocol of the SFOP (French Pediatric Oncology Society) [abstract]. Proc Am Soc Clin Onclol. 1992;11. 24. Pui CH, Relling MV, Lascombes F, et al. Urate oxidase in prevention and treatment of hyperuricemia associated with lymphoid malignancies. Leukemia. 1997;11:1813-1816[CrossRef][Medline] [Order article via Infotrieve].
25.
Smalley RV, Guaspari A, Haase-Statz S, Anderson SA, Cederberg D, Hohneker JA.
Allopurinol: intravenous use for prevention and treatment of hyperuricemia [published erratum appears in J Clin Oncol. 2000 May;18(10):2188].
J Clin Oncol.
2000;18:1758-1763
© 2001 by The American Society of Hematology.
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  C James, A Gupta, D Cheng, S Padley, N Goulden, and S Skellett A boy frightened of going to bed and bumps in the night BMJ, September 29, 2009; 339(jul22_4): b2787 - b2787. [Full Text]
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 J. H. Feusner, A. K. Ritchey, S. L. Cohn, and A. L. Billett Management of Tumor Lysis Syndrome: Need for Evidence-Based Guidelines J. Clin. Oncol., December 1, 2008; 26(34): 5657 - 5658. [Full Text] [PDF]
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|
|
B. Coiffier, A. Altman, C.-H. Pui, A. Younes, and M. S. Cairo In Reply J. Clin. Oncol., December 1, 2008; 26(34): 5658 - 5659. [Full Text] [PDF]
|
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 |
|
 P. Tosi, G. Barosi, C. Lazzaro, V. Liso, M. Marchetti, E. Morra, A. Pession, G. Rosti, A. Santoro, P. L. Zinzani, et al. Consensus conference on the management of tumor lysis syndrome Haematologica, December 1, 2008; 93(12): 1877 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Coiffier, A. Altman, C.-H. Pui, A. Younes, and M. S. Cairo 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. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hochberg and M. S. Cairo Tumor lysis syndrome: current perspective Haematologica, January 1, 2008; 93(1): 9 - 13. [Full Text] [PDF]
|
|
|
|
|
|
P. Montesinos, I. Lorenzo, G. Martin, J. Sanz, M. L. Perez-Sirvent, D. Martinez, G. Orti, L. Algarra, J. Martinez, F. Moscardo, et al. Tumor lysis syndrome in patients with acute myeloid leukemia: identification of risk factors and development of a predictive model Haematologica, January 1, 2008; 93(1): 67 - 74. [Abstract] [Full Text] [PDF]
|
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|
|
 |
|
 A. S. Perkins and J. W. Friedberg Burkitt Lymphoma in Adults Hematology, January 1, 2008; 2008(1): 341 - 348. [Abstract] [Full Text] [PDF]
|
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|
 |
|
 M. S. Cairo, M. Gerrard, R. Sposto, A. Auperin, C. R. Pinkerton, J. Michon, C. Weston, S. L. Perkins, M. Raphael, K. McCarthy, et al. Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents Blood, April 1, 2007; 109(7): 2736 - 2743. [Abstract] [Full Text] [PDF]
|
|
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|
 |
|
 V. Stove, B. Wuyts, and J. Delanghe Perchloric Acid Treatment To Stabilize Uric Acid Concentrations in Blood Samples of Patients Receiving Uric Acid Oxidase (Rasburicase) Therapy Clin. Chem., February 1, 2007; 53(2): 369 - 370. [Full Text] [PDF]
|
|
|
|
 |
|
 M Trujillo and M Morales Rasburicase-induced fatal respiratory arrest? Ann. Onc., February 1, 2007; 18(2): 399 - 400. [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Khan, C. Deel, and R. N. Hellman Tumor Lysis Syndrome Associated With Reduced Immunosuppression in a Lung Transplant Recipient Mayo Clin. Proc., October 1, 2006; 81(10): 1397 - 1399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M McNutt, M. T Holdsworth, C. Wong, J. D Hanrahan, and S. S Winter Rasburicase for the Management of Tumor Lysis Syndrome in Neonates Ann. Pharmacother., July 1, 2006; 40(7): 1445 - 1450. [Abstract] [Full Text] [PDF]
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 B. Vogt Urate oxidase (rasburicase) for treatment of severe tophaceous gout Nephrol. Dial. Transplant., February 1, 2005; 20(2): 431 - 433. [Full Text] [PDF]
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 B. D. Humphreys, R. J. Soiffer, and C. C. Magee Renal Failure Associated with Cancer and Its Treatment: An Update J. Am. Soc. Nephrol., January 1, 2005; 16(1): 151 - 161. [Full Text] [PDF]
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 B. Bickert and A. Reilly Pediatric Tumor Lysis Syndrome Journal of Pharmacy Practice, December 1, 2004; 17(6): 447 - 454. [Abstract] [PDF]
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 Y. Bertrand, A. Auvrignon, B. Nelken, V. Mialou, F. Mechinaud, B. Brethon, C. Patte, D. Plantaz, M. Urbieta, A. Baruchel, et al. Recommandations of the Societe Francaise des Cancers de l'Enfant (SFCE) for the Management of Tumors Lysis Syndrom (TLS) : A Validation Survey. Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 5295 - 5295. [Abstract]
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T. M Arnold, J. P Reuter, B. S Delman, and C. B Shanholtz Use of Single-Dose Rasburicase in an Obese Female Ann. Pharmacother., September 1, 2004; 38(9): 1428 - 1431. [Abstract] [Full Text] [PDF]
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B. Coiffier In Reply: J. Clin. Oncol., August 15, 2004; 22(16): 3431 - 3432. [Full Text] [PDF]
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H. van den Berg and A. M. Reintsema Renal tubular damage in rasburicase: risks of alkalinisation Ann. Onc., January 1, 2004; 15(1): 175 - 176. [Full Text] [PDF]
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B. Coiffier, N. Mounier, S. Bologna, C. Ferme, H. Tilly, A. Sonet, B. Christian, O. Casasnovas, E. Jourdan, K. Belhadj, et al. Efficacy and Safety of Rasburicase (recombinant urate oxidase) for the Prevention and Treatment of Hyperuricemia During Induction Chemotherapy of Aggressive Non-Hodgkin's Lymphoma: Results of the GRAAL1 (Groupe d'Etude des Lymphomes de l'Adulte Trial on Rasburicase Activity in Adult Lymphoma) Study J. Clin. Oncol., December 1, 2003; 21(23): 4402 - 4406. [Abstract] [Full Text] [PDF]
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A. C. Lee, C. H Li, K. T So, and R. Chan Treatment of Impending Tumor Lysis with Single-Dose Rasburicase Ann. Pharmacother., November 1, 2003; 37(11): 1614 - 1617. [Abstract] [Full Text] [PDF]
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E. Lim, P. Bennett, and J. Beilby Sample Preparation in Patients Receiving Uric Acid Oxidase (Rasburicase) Therapy Clin. Chem., August 1, 2003; 49(8): 1417 - 1419. [Full Text] [PDF]
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B. T Yim, R. P Sims-McCallum, and P. H Chong Rasburicase for the Treatment and Prevention of Hyperuricemia Ann. Pharmacother., July 1, 2003; 37(7): 1047 - 1054. [Abstract] [Full Text] [PDF]
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| Copyright © 2001 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
Top
Abstract
Introduction
86.0% for the rasburicase group
and