Effectiveness of Single-dose Rasburicase in Patients With Lymphoid Malignancies at a High Risk for Tumor Lysis Syndrome

BackgroundTumor lysis syndrome (TLS) is a life-threatening disorder that occurs mainly in patients with high-tumor burden hemato-oncologic malignancies. It results in metabolic derangements, including hyperuricemia and acute renal failure. The powerful management for TLS is a daily dose of rasburicase for up to 5 days before chemotherapy; however, the optimal dose and duration of rasburicase for TLS prophylaxis have not been standardized for patients at high risk for TLS. Therefore, we evaluated the efficacy of single-dose rasburicase for prophylactic purposes in patients with malignant lymphoma at high risk for TLS.Patients and MaterialsWe retrospectively evaluated patients with malignant lymphoma at high risk for TLS treated with a prophylactic single-dose of rasburicase (0.1-0.2 mg/kg) from March 2012 to March 2016.ResultsA total of 67 patients treated with a single-dose of rasburicase for prophylaxis were analyzed. A relatively large number of patients (n = 23; 34.3%) had the highly proliferative lymphoblastic lymphoma subtype (n = 14) or Burkitt lymphoma (n = 9) and were at the highest risks of tumor lysis. Two patients were newly diagnosed with TLS; the incidence of TLS after single-dose prophylaxis was 3.0%. Multivariate analysis revealed no predictable risk factors for response to prophylactic rasburicase, though increased level of serum creatinine approached statistical significance in reducing the efficacy of single-dose rasburicase to prevent TLS (odds ratio, 3.61; P = .054).ConclusionOur data indicated that single-dose rasburicase effectively prevented progression of TLS, and, regardless of any risk factors, including increased creatinine, single-dose rasburicase for TLS prophylaxis was useful in patients with lymphoma at a high risk for TLS.     

A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome

BackgroundTumor lysis syndrome (TLS) is a life-threatening disorder characterized by hyperuricemia and metabolic derangements. The efficacy of rasburicase, administered daily for 5 days, has been well established. However, the optimal duration of therapy is unknown in adults.Patients and methodsWe evaluated the efficacy of rasburicase (0.15 mg/kg) administered as single dose followed by as needed dosing (maximum five doses) versus daily dosing for 5 days in adult patients at risk for TLS.ResultsEighty of the 82 patients enrolled received rasburicase; 40 high risk [median uric acid (UA) 8.5 mg/dl; range, 1.5–19.7] and 40 potential risk (UA = 5.6 mg/dl; range, 2.4–7.4). Seventy-nine patients (99%) experienced normalization in their UA within 4 h after the first dose; 84% to an undetectable level (<0.7 mg/dl). Thirty-nine of 40 (98%) patients in the daily-dose arm and 34 of 40 (85%) patients in single-dose arm showed sustained UA response. Six high-risk patients within the single-dose arm required second dose for UA >7.5 mg/dl. Rasburicase was well tolerated; one patient with glucose-6-phosphate dehydrogenase deficiency developed methemoglobinemia and hemolysis.ConclusionsRasburicase is highly effective for prevention and management of hyperuricemia in adults at risk for TLS. Single-dose rasburicase was effective in most patients; only a subset of high-risk patients required a second dose.     

Single-Dose Rasburicase Might Be Adequate To Overcome Tumor Lysis Syndrome In Hematological Malignancies

IntroductionTumor lysis syndrome (TLS) is a commonly observed oncological emergency that requires prompt diagnosis and treatment. Rasburicase is a recombinant urate oxidase endorsed in TLS for the treatment of hyperuricemia. The effect of single-dose 7.5 mg rasburicase at longer follow-ups was not widely investigated.Patients and MethodsEighty-two patients included in the study with clinical TLS and laboratory TLS. The primary endpoint was the normalization of uric acid (<6mg/dL) within 24 hours of rasburicase administration, which was described as treatment success. The secondary endpoint was defined as having sustained response at the first week. The third endpoint was defined as the reaching the baseline renal function before TLS.ResultsWe found that the use of a 7.5 mg dose of rasburicase controlled uric acid in 74 of 82 (90,2%) patients at the 24th hour. In the first week, uric acid remained at normal levels in 69 of 82 (84,1%) patients. At 24 hours, the TLS risk group was the only predictor for failing uric acid normalization; at the end of the first week, no predictive factor was identified for failing uric acid normalization.ConclusionRasburicase at 7.5 mg dose is an important agent for controlling laboratory and clinical TLS at 24 hours and extending its effect to the first week.     

The management of tumor lysis syndrome

The manifestation of tumor lysis syndrome (TLS) occurs when the destruction of tumor cells releases breakdown products that overwhelm the excretory mechanisms of the body. A cardinal sign is hyperuricemia, leading to uric acid nephropathy. Other signs are hyperkalemia, hyperphosphatemia and secondary hypocalcemia. Conventional management of TLS consists of aggressive intravenous hydration, diuretic therapy, urinary alkalization, and inhibition of urate production by high-dose allopurinol. Urate oxidase has been used in the management of patients at risk for TLS and recently the recombinant urate oxidase rasburicase was developed. Several data indicate that rasburicase is effective and well tolerated in the prevention and treatment of chemotherapy-induced hyperuricemia. Treatment options of hyperkalemia include sodium polystyrene sulfonate, hypertonic glucose and insulin, loop diuretics, and bicarbonate. Treatment of hyperphosphatemia reduces dietary phosphate intake and includes phosphate binders such as aluminum hydroxide and aluminum carbonate. When recurrent hypocalcemia is present, a continuous intravenous infusion of calcium gluconate can be initiated. Hemodialysis should be considered for every patient with excessively elevated uric acid, phosphate and/or potassium and in those patients with acute renal failure to control urinary volume and manage uremia.     

Recombinant urate oxidase for prevention of hyperuricemia and tumor lysis syndrome in lymphoid malignancies

Hyperuricemia is a common manifestation of lymphoid malignancies at diagnosis or after the start of chemotherapy. When accompanied by other metabolic abnormalities and/or organ failure, hyperuricemia may be a manifestation of tumor lysis syndrome (TLS). Patients at particularly high risk of such complications include those with acute lymphoblastic leukemia and advanced stage non-Hodgkin's lymphoma. Conventional measures to prevent hyperuricemia and TLS are comprised of hydration, alkalinization of body fluids, and administration of allopurinol. Although these measures are usually effective in preventing or managing hyperuricemia, approximately 20% of patients at high risk of TLS require dialysis, and many cannot receive chemotherapy as planned. Rasburicase, a recombinant form of the enzyme urate oxidase, has recently become available and may further reduce the morbidity of hyperuricemia and TLS. In this review, we provide an overview of hyperuricemia and TLS and discuss the impact of rasburicase in the overall management of these complications.     

Management of tumor lysis syndrome with a single fixed dose of rasburicase in Asian lymphoma patients: a case series and literature review

Aim: Recently, a number of studies have demonstrated the effectiveness of a single reduced dose of rasburicase for the management of tumor lysis syndrome (TLS) in adults. Whether Asian lymphoma patients similarly respond to a single dose of rasburicase is currently unknown. We aim to assess the efficacy of a single dose rasburicase in preventing TLS in Asian lymphoma patients. Methods: This was a single‐center case series of adult lymphoma patients at high risk of TLS who received a single fixed dose of rasburicase. Patients had to have their uric acid, serum creatinine, lactate dehydrogenase and electrolytes monitored for at least 24–48 h post‐administration. Results: Eleven patients were identified. Majority were Chinese (91%), male (64%) and with a median age of 61 years (range 41–84). All had at least two risk factors for developing TLS. Ten patients received a 6‐mg dose and one received 4.5 mg. Prior to rasburicase administration, the mean uric acid level was 835 µmol/L (range 318–1237 µmol/L) and the level 24‐h post‐administration was 186 µmol/L (range 30–653 µmol/L) (P < 0.001). Eight patients (73%) experienced an improvement of renal function 72‐h post‐rasburicase. Normalization of serum electrolytes was achieved within 96 h. Conclusion: Among Asian lymphoma patients who manifested at least two risk factors for developing TLS, a single fixed dose of rasburicase at 6 mg is deemed to be effective for rapidly lowering uric acid levels as well as sustaining reduced levels for up to 72 h.     

Acute tumor lysis syndrome in solid tumors—a case report and review of the literature

PURPOSE: Tumor lysis syndrome (TLS) is a potential complication in cancer therapy. It may occur in highly sensitive tumors, especially in childhood cancers and acute leukemias, whereas it is rare in the treatment of adult solid tumors. TLS is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia following massive lysis of malignant cells. Complications include acute renal failure and metabolic acidosis. We report the first case of TLS during chemotherapy in a patient with metastatic medulloblastoma, together with a review of the literature regarding the occurrence of TLS in patients with solid tumors. METHODS: Data regarding clinical and biochemical parameters were extracted from the actual patients' files. Reports of TLS in the English language literature up to 2002 were identified by searching Medline. RESULTS: A 23-year old male with metastatic medulloblastoma received chemotherapy with cisplatin and etoposide due to massive extracerebral manifestations including metastases to the liver, mediastinal lymph nodes and bone marrow metastases. The patient developed classical signs of TLS on the second day of chemotherapy, including acute renal failure. A 17-fold increase in plasma LDH up to 87608 U/l was observed together with a 4-fold increase in plasma creatinine. The patient was treated with aggressive hydration, allopurinol and repeated hemodialysis. During the following days the patient improved and the biochemical markers all returned to normal. REVIEW. Reviewing the literature, a total of 45 patients with solid tumors who developed TLS have been reported. Most of the patients presented with metastatic, therapy-sensitive disease. Although preventable in practically 100% of patients, TLS is a potentially fatal complication, and in this material the mortality rate was one in three. Risk factors included increased LDH, hyperuricemia and pretreatment azotemia. CONCLUSIONS: TLS is only rarely associated with treatment of solid tumors. Precautions should be taken to avoid this potentially fatal complication in (chemo)therapy of solid tumors, especially in therapy-sensitive tumors presenting with bulky, metastatic disease and preexisting risk factors, including azotemia, elevated LDH and hyperuricemia. Prophylactic treatment to avoid TLS includes allopurinol, hydration prior to treatment and alkalization of the urine. Urate oxidase (rasburicase) is now beginning to replace allopurinol as a more effective way of reducing hyperuricemia and thereby the risk of TLS.     

Efficacy of Single Low-Dose Rasburicase in Management of Tumor Lysis Syndrome in Leukemia and Lymphoma Patients

BackgroundTumor lysis syndrome (TLS) is a metabolic emergency in hematology patients. The recommended dose of rasburicase for the management of TLS is 0.2 mg/kg per day for 5 days, which is cost prohibitive for many patients. We sought to determine the efficacy of single low-dose rasburicase in the prevention and treatment of hyperuricemia in TLS.Patients and MethodsWe planned a prospective study for the safety and efficacy of fixed (weight based) dose of rasburicase to manage TLS. Patients diagnosed with leukemia/lymphoma with laboratory or clinically confirmed TLS or presence of ≥ 2 high-risk factors and serum uric acid > 7.5 mg/dL were included. The primary endpoint was uric acid normalization (< 7.5 mg/dL) within 24 hours of rasburicase administration.ResultsFifty-five patients were recruited for this study. Pediatric patients (< 18 years) accounted for 43.6% of cases. Rasburicase was provided prophylactically to 43 patients (78.2%) and for treating TLS to 12 (21.8%). Mean ± standard deviation serum uric acid at baseline and 24 hours was 9.2 ± 1.8 mg/dL and 3.2 ± 2.1 mg/dL, respectively. There was significant reduction in the serum uric acid and creatinine (P < .001) within 24 hours of rasburicase administration. The response was maintained up to 72 hours. A single dose of rasburicase was effective in 94.5% of patients. Single low-dose rasburicase led to 95% direct cost savings compared to the recommended dose.ConclusionSingle-dose rasburicase with frequent laboratory monitoring is effective in the management of TLS and offers significant cost reductions.     

The Effective Control of Hyperuricemia in Cancer Patients: A New Recombinant Conjugated Variant of Urate Oxidase

Objective: Management of hyperuricemia is crucial to controlling tumor lysis syndrome (TLS) during cancer therapy. Urate oxidase (UOX) that catalyzes the enzymatic oxidation of uric acid into allantoin, is effective in lowering plasma uric acid levels and controlling hyperuricemia. Recently, we developed a new recombinant conjugate variant of UOX therapeutic drug using PASylation technology. This study was designed to evaluate the stability, plasma half-life and immunogencity of PASylated UOX. Methods: A recombinant variant of PASylated UOX from the Aspergillus flavus was manufactured using bioinformatics and experimental techniques. Ex vivo evaluation of stability of PASylated UOX was done in 50% human serum. For half-life test, recombinant PASylated UOX and rasburicase were administered at 1.5 mg/kg to 10 rats in two different groups and samples were collected after injection Production of antibodies against PASylated drug was also assayed. Results: Residual activity of PASylated UOX in 50% human serum was higher than rasburicase and native UOX. Stability of PASylated UOX at 25°C and 37°C was also higher than rasburicase and native UOX. The PASylated half-life was ~32.1 hours, whereas half-life for rasburicase and native UOX was ~25.1 and ~22.8 hours, respectively. In immunogenicity examination, there is 33% and 36% decrease in the absorbance of native UOX and rasburicase, respectively when compared with that of PASylated UOX. Conclusion: Our data confirmed the efficacy and stability of PASylated UOX in comparison to the rasburicase. In summary, the results indicated that PASylated UOX drug is effective at lowering plasma uric acid levels with prolonged plasma half-life and decreased cost.     

Rasburicase (recombinant urate oxidase) for the management of hyperuricemia in patients with cancer: report of an international compassionate use study

BACKGROUND: Hyperuricemia and tumor lysis syndrome (TLS) are serious complications that can occur during chemotherapy for hematologic malignancies, even if standard management procedures, including administration of allopurinol, are undertaken. Rasburicase, a recombinant urate oxidase that converts uric acid (UA) into the soluble compound allantoin, has been shown to control hyperuricemia faster and more reliably than allopurinol.(1) METHODS: A compassionate use trial, running from January 1999 to December 2001, provided access to rasburicase for patients in nine countries who were at risk for TLS during the initiation of chemotherapy. Of the 280 patients enrolled in the study, 278 received rasburicase and were included in the analysis. A total of 166 pediatric patients who had leukemia (approximately 74%), lymphoma (approximately 24%), or solid tumors (approximately 3%) were treated with rasburicase. One hundred twelve adults with either leukemia (68%) or lymphoma (30%) also were treated. Rasburicase (0.20 mg/kg) was administered intravenously once a day for 1 to 7 days, at the investigator's discretion. Two doses daily could be administered during the first 3 days. A response was defined as a reduction in UA level or maintenance of a UA level less than 7.5 mg/dL (or less than 6.5 mg/dL, for children age < 13 years). RESULTS: UA levels at 24-48 hours after administration of the last dose of rasburicase were available for 122 pediatric patients and 97 adult patients. The mean UA level in 29 hyperuricemic children decreased from 15.1 mg/dL to 0.4 mg/dL, whereas in 27 hyperuricemic adults, the mean level decreased from 14.2 mg/dL to 0.5 mg/dL. Prophylactic administration of rasburicase to prevent TLS during chemotherapy reduced UA levels from a mean of 4.4 mg/dL to 0.8 mg/dL in 93 nonhyperuricemic children and from 4.8 mg/dL to 0.4 mg/dL in 70 nonhyperuricemic adults (for all reductions in UA levels, P < 0.001). The response rate was 100%. Rasburicase was very well tolerated. Serious adverse events related to rasburicase were observed in one patient. CONCLUSIONS: The results of the current study confirm that rasburicase is safe and highly effective in the prevention and treatment of chemotherapy-induced hyperuricemia in both children and adults.     

A Clinical and Economic Comparison of Rasburicase and Allopurinol in the Treatment of Patients With Clinical or Laboratory Tumor Lysis Syndrome

BackgroundThe aim of the study was to compare reductions in uric acid (UA), length of stay (LOS), and hospitalization costs in patients with tumor lysis syndrome (TLS) treated with rasburicase or allopurinol.Patients and MethodsThis retrospective study of administrative data included hospitalized pediatric and adult patients who had clinical or laboratory TLS and received rasburicase or allopurinol. Each rasburicase-treated patient was propensity score-matched with 4 allopurinol-treated patients. Mean changes in UA within ≤ 2 days of treatment initiation were determined. Economic outcomes included mean number of days in the intensive care unit (ICU), total LOS, costs/hospitalization, and costs/percentage change in UA.ResultsTwenty-six rasburicase-treated patients were matched with 104 allopurinol-treated patients. Reduction in plasma UA was 5.3 mg/dL greater for patients treated with rasburicase than for patients treated with allopurinol (P < .0001). Length of ICU stay was 2.5 days less for patients treated with rasburicase than for patients treated with allopurinol (P < .0001), and total LOS was 5 days less for patients treated with rasburicase than for patients treated with allopurinol (P = .02). Total costs per patient were $20,038 lower for patients treated with rasburicase than for patients treated with allopurinol (P < .02). Cost per percentage UA reduction was also lower for patients treated with rasburicase versus patients treated with allopurinol ($3899 vs. $16,894; P < .001).ConclusionIn this analysis of TLS patients who received care in real-world settings, rasburicase versus allopurinol was significantly more effective in treating hyperuricemia and was associated with significantly shorter ICU and overall hospital stays and lower total inpatient costs.     

Prevention and treatment of hyperuricemia in hematological malignancies

The standard prophylactic and treatment regimen for hyperuricemia in patients with hematological malignancies previously included vigorous hydration, urinary alkalinization, and a xanthine oxidase inhibitor, allopurinol, which blocks the conversion of hypoxanthine and xanthine to uric acid. However, xanthine is less soluble than uric acid, and preexisting uric acid is not affected by allopurinol. The enzyme urate oxidase, not present in mammals, converts uric acid to allantoin, which is 5-10 times more soluble than uric acid. A new recombinant form of urate oxidase, rasburicase, has recently been developed. In a phase I/II study of rasburicase in children and young adults with hematological malignancies, rasburicase was demonstrated to be well tolerated at 0.2 mg/kg/day intravenously, had a mean T1/2 of 21.2 +/- 12.0 hours, and induced a median decrease in uric acid from 9.7 mg/dL to 1.0 mg/dL (P < 0.001). We recently demonstrated, in a randomized prospective trial comparing rasburicase versus allopurinol in children with hematological malignancies at high risk of tumor lysis syndrome, that rasburicase significantly lowered the mean uric acid area under the curve 0 to 96 hours (128 +/- 70 mg/dL/hour vs. 329 +/- 129 mg/dL/hour; P < 0.001) and 4 hours post uric acid by 86% versus 12% (P < 0.001). Furthermore, in the hyperuricemic group, the baseline creatinine level decreased from 144% to 102% by 96 hours following rasburicase compared to an increase from 132% to 147% following allopurinol. Although the difference in effect on creatinine levels is not significant, the study was not designed or powered to question this effect. Lastly, in 510 patients with hematological malignancies at risk for tumor lysis syndrome who received rasburicase, only 2 (0.4%) have developed new renal complications requiring hemodialysis. In summary, in the prevention and treatment of hyperuricemia, patients with hematological malignancies at risk of tumor lysis syndrome appear to benefit significantly from the use of a recombinant urate oxidase (rasburicase).     

Single dose rasburicase in tumor lysis: One hospital's experience

Background: Tumor lysis syndrome is an oncological emergency occurring mainly in high‐grade hematological malignancies. It results in significant biochemical abnormalities including hyperuricemia and acute renal failure. Rasburicase is a recombinant urate oxidase enzyme that catalyzes oxidation of uric acid into allantoin, which is easily excreted in the urine. Reports in the literature suggest that a single dose of rasburicase is effective in treating tumor lysis syndrome, whereas the current dose recommended by the manufacturer is 0.2 mg/kg/day for 5 to 7 days, which is very costly ($13 000 for an average 70‐kg person). We present a retrospective analysis on the patients at our hospital that have received rasburicase as a single dose. Methods: Medical and pharmacy dispensing records were searched to identify patients with high‐grade hematological malignancy who received a single dose of rasburicase in a 12‐month period. Data on renal function, electrolytes, and uric acid were obtained. Results: Twenty‐three patients were newly diagnosed with high‐grade hematological malignancy (Burkitt lymphoma 4, AML 17, APML 1, DLBCL 1). A single dose of rasburicase 0.2 mg/kg was administered to six of these patients considered to be at high risk, five of whom had an elevated uric acid level before treatment. Their uric acid levels were monitored from 24 h to 96 h after this dose. Normal uric acid levels were seen in all patients within 24 h. These levels remained normal for 96 h. One of five patients died of pre‐existing renal failure despite the normalization of their uric acid. Conclusion: We conclude that single dose rasburicase is effective in the treatment of hyperuricemia in patients at risk of tumor lysis and effectively reduces the level of uric acid for up to 96 h. This makes it cost effective and theoretically reduces the risk of hypersensitivity associated with rasburicase.     

A single dose of rasburicase is sufficient for the treatment of hyperuricemia in patients receiving chemotherapy

Hydration, urinary alkalization, and allopurinol are the standard of care in the treatment and prevention of hyperuricemia. Rasburicase is a new alternative for the management of hyperuricemia in cancer patients. Criteria for the use of rasburicase were developed by the Hematology/Oncology Pharmacy and Therapeutics Subcommittee of the Detroit Medical Center and implemented in 2003. The guidelines limit rasburicase use to one dose, with additional doses as needed, compared to the five doses recommended by the manufacturer, in cancer patients with hyperuricemia and bulky tumor who require immediate chemotherapy. During the period of March to September 2003, eight patients received rasburicase, according to the guidelines, for the management of hyperuricemia. One dose of rasburicase produced a rapid and sustained therapeutic effect of lowering the plasma uric acid levels in all patients. The levels remained below 4 mg/dL throughout the administration of chemotherapy for up to 96 h. Utilizing the guidelines resulted in a significant cost savings of 100,000 US dollars.     

Management of tumor lysis syndrome in adults

Spontaneous or treatment-induced tumor lysis syndrome (TLS) can cause significant morbidity and potential mortality. Vigorous hydration, alkalinization and inhibition of uric acid synthesis with allopurinol are the most frequently used methods for treatment and prevention of TLS. However, this approach fails to prevent renal insufficiency in up to 25% of high-risk patients. With the increased intensity and efficacy of cancer therapies, novel approaches for the management of TLS are needed. Unlike allopurinol, urate oxidase promptly reduces the existing uric acid pool, prevents accumulation of xanthine and hypoxanthine and does not require alkalinization, facilitating phosphorus excretion. A recombinant form of urate oxidase, rasburicase, is now registered for the treatment and prevention of TLS. This review provides an overview of rasburicase development and discusses the impact of rasburicase in the prevention and management of TLS.     

Management of tumor lysis syndrome in adults

Spontaneous or treatment-induced tumor lysis syndrome (TLS) can cause significant morbidity and potential mortality. Vigorous hydration, alkalinization and inhibition of uric acid synthesis with allopurinol are the most frequently used methods for treatment and prevention of TLS. However, this approach fails to prevent renal insufficiency in up to 25% of high-risk patients. With the increased intensity and efficacy of cancer therapies, novel approaches for the management of TLS are needed. Unlike allopurinol, urate oxidase promptly reduces the existing uric acid pool, prevents accumulation of xanthine and hypoxanthine and does not require alkalinization, facilitating phosphorus excretion. A recombinant form of urate oxidase, rasburicase, is now registered for the treatment and prevention of TLS. This review provides an overview of rasburicase development and discusses the impact of rasburicase in the prevention and management of TLS.     

Challenges in the management of Burkitt's lymphoma

Burkitt's lymphoma and small noncleaved Burkitt's-like lymphoma are rare and are highly aggressive forms of non-Hodgkin's lymphoma that are characterized by dysregulation of the c-myc oncogene. Patients with human immunodeficiency virus (HIV) also appear to be at risk for developing Burkitt's lymphomas. Treatment options for Burkitt's lymphoma involve complex chemotherapy regimens that contain as many as 10 cytotoxic agents. Approximately 50%-80% of adult patients with Burkitt's lymphoma or small, noncleaved lymphoma can be cured with these intensive chemotherapy regimens, and in pediatric populations, the cure rate is even higher. However, a number of factors often compromise the outcome of patients with Burkitt's lymphoma. For instance, the high proliferation rate of Burkitt's lymphoma enhances the risk for tumor lysis syndrome, which results from metabolic imbalances, such as hyperuricemia, that occur as large numbers of malignant cells are lysed during cytotoxic chemotherapy. Standard treatment for tumor lysis syndrome includes adjustments in the chemotherapy regimen, vigorous hydration, administration of a uric acid synthesis inhibitor like allopurinol, and alkalinization. The administration of recombinant urate oxidase (rasburicase) also has been shown to provide effective prophylaxis against hyperuricemia in pediatric and adult patients with hematologic malignancies. The lifetime risk of developing central nervous system disease is 20%-30% for Burkitt's lymphoma. Consequently all chemotherapy regimens with activity in Burkitt's lymphoma utilize some form of central nervous system prophylaxis, such as systemic or intrathecal methotrexate or cytarabine. In the past, patients with HIV who developed Burkitt's lymphoma often received inadequate chemotherapy doses because of their immunosuppression. With the discovery of highly active antiretroviral therapy, the ability to treat and control Burkitt's lymphoma in patients with HIV has improved.     

Elitek-rasburicase: an effective means to prevent and treat hyperuricemia associated with tumor lysis syndrome, a Meeting Report, Dallas, Texas, January 2002.

Renal precipitation of uric acid associated with tumor lysis syndrome (TLS) is a major complication in the management of leukemia, lymphoma, and other drug-sensitive cancers. Management of hyperuricema has historically consisted of administration of allopurinol, hydration, alkalinization to maintain pH between 7.0 and 7.3, and in some cases diuresis. Allopurinol, a xanthine analogue, blocks xanthine oxidase and formation of uric acid. Urate oxidase converts uric acid to allantoin, which is 5-10 times more soluble than uric acid. Homo sapiens cannot express urate oxidase because of a nonsense mutation. Urate oxidase was initially purified from Aspergillus flavus fungus. Treatment with this nonrecombinant product had been effective in preventing renal precipitation of uric acid in cancer patients, but was associated with a relatively high frequency of allergic reactions. This enzyme was recently cloned from A. flavus and is now manufactured as a recombinant protein. Clinical trials have shown this drug to be more effective than allopurinol for prevention and treatment of hyperuricemia in leukemia and lymphoma patients. This drug has been approved in Europe as well as the US and several clinical trials are in progress to further determine its clinical utility in other patient subsets. The purpose of this meeting was to discuss usefulness of recombinant urate oxidase, also known as rasburicase, Fasturtec, and Elitek, for the management of TLS in certain cancer patients.     

急性淋巴细胞白血病并发肿瘤溶解综合征7例

目的 :探讨急性淋巴细胞白血病 (AL L )患者化疗后发生肿瘤溶解综合征 (TL S)的临床特征。方法 :对 7例化疗发生 TL S的 AL L患者进行各项生化指标的分析。结果 :TL S患者表现为高尿酸血症、高血钾、高血磷、低血钙 ,并有不同程度的肾功能损伤 ,其中 1例发生了急性肾功能不全。用别嘌呤醇及静脉碱化利尿后 ,6例短期内血生化指标恢复正常。1例死于心衰。结论 :早期诊断并及时给予别嘌呤醇及静脉碱化利尿是治疗 TL S的关键     

儿童急性淋巴细胞白血病并发肿瘤溶解综合征18例临床分析

目的:探讨儿童急性淋巴细胞白血病（acute lymphoblastic leukemia,ALL）并发肿瘤溶解综合征（tumor lysis syndrome,TLS）的临床特点,分析TLS的危险因素以及预后。方法:回顾性收集2015年01月01日至2020年06月30日期间于我院就诊的253例ALL患儿的临床资料。分析TLS的危险因素以及TLS对ALL患儿预后的影响。结果:253例患儿中,18例（7.1%）患儿发生TLS,男女比例2.6∶1,中位年龄8.1岁。TLS患儿较非TLS患儿更容易出现窦性心动过速、前臂心肌复极异常以及QT间期延长（P<0.05）。初诊高白细胞计数（WBC≥50×109/L）与初诊非高白细胞TLS患儿的血尿酸、LDH、血肌酐、血钾、血校正钙及肌酐清除率（creatinine clearance,Ccr）之间没有统计学差异（P>0.05）。多因素分析显示初诊LDH≥900 U/L是TLS发生的独立危险因素。TLS组与非TLS组的EFS及OS没有统计学差异（P>0.05）。结论:初诊LDH≥900 U/L是TLS发生的独立危险因素。TLS并不影响ALL患儿的远期预后。