tumor lysis syndrome ( tls ) occurs in malignancies that have high proliferative potential and high tumor burden , such as lymphomas and leukemias .
it is characterized by rapid release of intracellular metabolites from lysed malignant cells into the blood stream .
the resulting metabolic derangements are hyperuricemia , hyperkalemia , hyperphosphatemia , and hypocalcemia , causing acute renal failure and which may lead to cardiac arrhythmias , seizures , and death .
the prevention and management of tls include aggressive hydration and reduction in the plasma uric acid levels by drugs that decrease production or increase excretion of uric acid . with the advent of rasburicase , a recombinant urate oxidase ,
there has been a tremendous decline in the tls - mediated renal failure and the need for dialysis .
but the recommended regimen and doses pose a heavy financial burden for the poor patients in developing countries like india . with data and studies proving a similar efficacy with reduced dose and lesser number of rasburicase
, it will be economical to devise a strategy that will help us to achieve reasonably comparable standards of efficiency , efficacy , and safety in tls management .
we report here a case series of seven children with acute leukemia , whose tls was managed by a single dose of rasburicase .
a retrospective analysis of case records of seven children with acute lymphoblastic leukemia ( all ) and tls , admitted to our pediatric oncology unit of our hospital between the period 2011 and 2013 , was done to evaluate the effectiveness of single - dose rasburicase ( sdr ) in the management of tls .
the children were administered a single dose of rasburicase at the rate of 0.15 mg / kg .
all patients were screened for glucose-6-phosphate dehydrogenase ( g6pd ) deficiency before the administration of rasburicase .
hemoglobin , white cell count , differential count , platelets , serum electrolytes , serum calcium , phosphorous , uric acid , blood urea nitrogen , and creatinine tests were done at the time of admission and repeated daily until the renal parameters and uric acid levels returned to normal levels .
the demographic details and clinical parameters of the children are enumerated in table 1 . demographic details and clinical parameters at the time of admission among the seven children ,
four had pre - b cell ( common all ) antigen - positive all and the other three had t - cell all determined by flow cytometry .
the highest and lowest uric acid levels at admission were 32.2 mg / dl and 9.7 mg / dl , respectively .
all of them had hypertension , hypocalcemia , hyperphosphatemia , and hyperuricemia and 3 had hyperkalemia .
all were managed with hyperhydration , anti - hypertensives , allopurinol , and a single dose of rasburicase at 0.15 mg / kg . the dose was rounded off to the nearest available concentration of vials due to the financial constraints .
a single dose of rasburicase produced a rapid and sustained therapeutic effect of lowering the plasma uric acid levels in all seven patients .
uric acid levels remained below 4 mg / dl throughout the administration of chemotherapy until discharge . depicting the serum uric acid and , creatinine levels and urine output before and after administering a single dose of rasburicase
acute renal failure is one of the most immediate , serious , and costly tls - related complication of treatment for hematologic malignancies .
hyperuricemia results from rapid catabolism of purine - containing nucleic acids from tumor cells and can lead to renal insufficiency when uric acid precipitates into the renal tubules and distal collecting system .
this causes renal vasoconstriction , which in turn leads to impaired autoregulation , decreased renal flow , oxidation and inflammation , finally leading to acute kidney injury . markedly increased phosphate levels compounded with calcium phosphate deposition in the renal tubules can also cause acute kidney injury .
high concentrations of both uric acid and phosphate potentiate the risk of acute kidney injury because uric acid precipitates more readily in the presence of calcium phosphate and vice versa .
allopurinol has been used for many years in the prevention and management of tls - related hyperuricemia .
allopurinol decreases the new production of uric acid by inhibiting enzyme xanthine oxidase and blocking oxidation of xanthine and hypoxanthine into uric acid . therefore ,
following allopurinol administration , there is a time lag for reduction in uric acid levels and hence should be administered for more than 3 days for the achievement of significant reduction in uric acid levels .
an alternative to inhibiting uric acid formation by inhibiting xanthine oxidase with allopurinol is to promote the catabolism of existing pool of uric acid to allantoin , which is 510 times more soluble in urine by urate oxidase .
rasburicase offers potential advantage over allopurinol because of its rapid onset of action , reducing pre - existing pool of uric acid within few hours , and also helping in avoiding accumulation of xanthine and hypoxanthine , which has poor water solubility and can worsen renal function .
urate oxidase is an endogenous enzyme commonly found in many mammalian species but not in humans because of nonsense mutation i , the coding region in the gene during hominoid evolution .
rasburicase is indicated for the prophylactic management as well as treatment of high plasma uric acid levels ( > 7.5 mg / dl ) in pediatric and adult patients with leukemia , lymphoma , and solid tumor malignancies , which have the highest risk of tumor lysis such as those with tumors that have a high proliferative rate(all , burkitt 's lymphoma ) , tumors with high sensitivity to cytotoxic therapy , patients with large tumor masses , and those with pre - existing renal insufficiency and high serum ldh levels .
it is administered as an intravenous ( iv ) infusion over 30 min and should never be given as a bolus .
the reconstituted solution can be stored at 28c for 24 h. repeated use of rasburicase increases risk of hypersensitivity reactions .
rasburicase was initially approved by the us food and drug administration for the management of tls in the pediatric setting , based on a randomized controlled phase iii clinical trial whereby rasburicase ( 0.15 or 0.2 mg / kg ) was administered for 5 consecutive days .
has confirmed the effectiveness and safety of rasburicase over allopurinol in children with hematologic malignancies .
rasburicase was administered at a dose of 0.2 mg / kg iv over 30 min for 57 days in this study population . though the efficiency and advantage of rasburicase has been proved beyond doubt more than a decade ago , it 's the cost of the product that has been the main inhibiting factor against its usage . in a developing country like india , where majority of the patients have to bear the brunt of the medical expenses with no insurance to support them , the use of rasburicase for 5 days is beyond the scope of the poor patients .
so , when several noncontrolled studies involving retrospective case series suggested shorter duration of treatment to minimize the cost but without compromising the efficacy , it was boon for children in resource limited settings .
evaluated the efficacy of a single dose rasburicase 0.15 mg / kg followed by as - needed dosing with a maximum of five doses instead of the standard 5-day regimen with 0.2 mg / kg in adult patients at risk for tls and concluded that single dose was effective in most patients and only a subset of high - risk patients received a second dose .
a study in south carolina depicted that a single dose of rasburicase 6 mg was effective in the management of tls in adults . in california ,
sdr for adult cancer patients with hyperuricemia or at high risk for tls demonstrated better response rate and stronger control of uric acid level compared with allopurinol .
sdr response rate was not inferior to that of daily - dose rasburicase ( ddr ) , and the standard - dose sdr generates more cost savings compared with the ddr . though majority of the studies had been in adult patients , lee et al
had proven the effectiveness of a single dose of rasburicase in three children with all and concluded that it is feasible and will improve the cost - effectiveness profile of the otherwise expensive compound .
all the children received a single dose of rasburicase , and their electrolyte abnormalities , and renal parameters , hyperuricemia and hypertension normalized in 72 h. the children were started on chemotherapy as per children 's oncology group protocol .
the uric acid levels were well below the normal levels during the entire period of chemo administration .
the rasburicase was administered on the day of admission in all our patients at the earliest and within 12 h of admission .
the time lag of 12 h in few patients was due to the financial constraints in arranging the drug .
our experience suggests that in appropriately monitored patients single dose followed by dosing as needed can be cost - saving . none of our patients required dialysis , which otherwise would have added to the economic burden .
administration of rasburicase does not require any expertise like catheters , central lines , intensive care unit care unlike dialysis , and no dose modifications are needed in spite of deranged renal parameters .
from an economic point of view , especially in a developing country like india , the promising single low - dose approach of rasburicase administration achieved satisfactory results with a great reduction of cost per patient , which can result in better cost - effectiveness with no compromise in clinical efficacy .
 tumor lysis syndrome ( tls ) occurs in malignancies with high proliferative potential and tumor burden , such as lymphomas and leukemias . 
 tls syndrome is an oncologic emergency , requiring prompt intervention . 
 the metabolic derangements cause acute kidney failure and may lead to cardiac arrhythmias , seizures , and death . with the advent of rasburicase , a recombinant urate oxidase , there has been a decline in the tls - mediated renal failure and the need for dialysis . the recommended regimen and doses 
 pose a heavy financial burden for patients in developing countries like india . with data and studies proving a similar efficacy for the reduced dose and lesser number of rasburicase , 
 we report here a case series of seven children with acute leukemias , whose tls was managed by a single dose of rasburicase . 
 a retrospective analysis of case records of seven children with acute lymphoblastic leukemia and tls , admitted to our pediatric oncology unit of our hospital between the period 2011 and 2013 , was done . 
 all our patients responded to a single dose , indicating that in appropriately monitored patients , single dose followed by as - needed dosing can be cost - saving . 