Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Recombinant urate oxidase for prevention of hyperuricemia and tumor lysis syndrome in lymphoid malignancies. 1267 72

To prevent acute renal failure in children at risk for developing tumor lysis syndrome due to acute lymphoblastic leukemia or non-Hodgkin's lymphoma treated according to international BFM protocols, we investigated recombinant urate oxidase (rasburicase) in the first Central European openlabeled, prospective, multicenter phase IV trial. Rasburicase was administered intravenously, at 0.2 mg/kg for 5 consecutive days to 36 patients. Blood levels of uric acid, creatinine, phosphorus, calcium, lactate dehydrogenase and complete blood count were measured daily during rasburicase treatment and on days 6, 7 and 12. Initial uric acid level decreased significantly by 4 hours (from 343 micromol/L to 58 micromol/L, p<0.001), except for one steroid-resistant patient who required hemodialysis on day 14 after having introduced combined cytostatic treatment. Comparing the data of a subgroup of 12 patients receiving rasburicase with that of a historic cohort of 14 patients treated with allopurinol indicated the superiority of rasburicase over allopurinol in prophylaxis and treatment of hyperuricemia in children with leukemia and lymphoma.
 ...
PMID:Prevention and treatment of hyperuricemia with rasburicase in children with leukemia and non-Hodgkin's lymphoma. 1738 90

Rasburicase is a recombinant urate-oxidase enzyme and is a very important medication for tumor lysis syndrome. Methemoglobinemia and hemolysis are known side effects of rasburicase that result from oxidative stress caused by hydrogen peroxide, a byproduct generated during the breakdown of uric acid to allantoin. Patients with G6PD deficiency have a decreased tolerance to oxidative stress and are therefore at a greater risk of hemolysis and methemoglobinemia with rasburicase. Our patient is a 56-year-old Caucasian male with a recent diagnosis of grade 2-3a non-Hodgkin's lymphoma who presented to our emergency department with shortness of breath and dark discoloration of urine. Patient was discharged 36 hours ago from our hospital after he was given a first course of R-CHOP regimen and a dose of rasburicase. On further evaluation, patient was found to have severe anemia with hemolytic picture, hyperkalemia and acute kidney injury. He also had a discrepancy of the transcutaneous saturation (75%) and the saturation in an arterial blood gas value (99%). His methemoglobin level was found to be 11.9%. We were aware that methylene blue is a contraindication in patients with G6PD deficiency but considering patient being Caucasian and low risk for it and his deteriorating respiratory condition, it was decided to offer the treatment and patient received 1 dose of methylene blue which failed to improve his methemoglobinemia. He was also given vitamin C and 8 units of packed red blood cell throughout his stay in the hospital. Patient's hospital course was complicated by ARDS needed to be on mechanical ventilation support for 4 days and acute renal failure secondary to pigment nephropathy and acute tubular necrosis which required a hemodialysis support. Even if rasburicase induced methemoglobinemia and hemolysis are not very common complications, clinicians who prescribe and follow patients should detect this serious complication early and manage it accordingly. Our case can be used as a reminder that patients should be followed closely and given the right instructions on discharge to treat these complications which are associated with severe consequences. It is also vital to assume a diagnosis of G6PD deficiency until proven otherwise in a patient who presents with rasburicase induced hemolysis and avoid administration of methylene blue even if the patient is from a low risk ethnicity for G6PD as in our patient.
 ...
PMID:Rasburicase induced severe hemolysis and methemoglobinemia in a Caucasian patient complicated by acute renal failure and ARDS. 3060 5

Aims: To conduct a lifetime cost-effectiveness analysis (CEA) of rasburicase compared with standard of care (SOC) for tumor lysis syndrome (TLS) in children with hematologic malignancies from the Chinese healthcare system perspective. Materials and methods: The CEA was performed using a decision tree model with a lifetime horizon. The model explores the cost-effectiveness of rasburicase vs SOC for both preventing TLS and treating established TLS among pediatric patients with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and non-Hodgkin's lymphoma (NHL). Both the prophylaxis-use model and treatment-use model incorporate long-term health states of the diseases: survival without TLS and death. The efficacy data of rasburicase and SOC were obtained from published literature. Drug costs, healthcare resource utilization (HRU), and adverse event (AE) management costs were obtained via a published study with clinical experts. Costs in US dollar and quality-adjusted life year (QALY) are reported, and incremental cost-effectiveness ratios (ICERs) were also calculated. Uncertainties due to parameter fluctuations in the model were assessed through one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). Results: During TLS prevention, compared with SOC, the ICER of rasburicase treatment in China are $17,580.04/QALY, $5,783.45/QALY, and $5,391.00/QALY for pediatric patients with AML, ALL, and NHL, respectively. For the established TLS treatment, compared with SOC, the ICERs of rasburicase treatment are $2,031.18/QALY, $1,142.93/QALY, and $990.37/QALY for pediatric patients with AML, ALL, and NHL, respectively. Limitations: The clinical data for SOC are based on the published study in China, and the rasburicase prevention or treatment failure rate was either calculated based on the risk ratio or directly from the clinical study among non-Chinese pediatric patients. Another study limitation was the lack of utility data for pediatric patients with TLS and without TLS. Thus, the utility scores of pediatric cancer survivors were used as an alternative. Conclusion: Rasburicase is estimated to be a cost-effective alternative to SOC in the prevention and treatment of TLS among Chinese pediatric patients with AML, ALL, and NHL.
 ...
PMID:Cost-effectiveness analysis of rasburicase over standard of care for the prevention and treatment of tumor lysis syndrome in children with hematologic malignancies in China. 3093 62