There are several different definitions of TLS which contain laboratory and clinical classifications, as can be found here [1]. According to Cairo and Bishop [2] laboratory TLS is diagnosed when two or more of the following metabolic abnormalities occur within 3 days before or up to 7 days after the initiation of therapy: hyperuricemia, hypocalcemia, hyperkalemia and hyperphosphatemia. They define clinical TLS as laboratory TLS accompanied by presence of acute kidney injury, seizures, cardiac dysrhythmia, or death. Acute kidney injury may result from urate nephropathy, endothelial dysfunction, local ischemia, or pro-inflammatory and pro-oxidative state secondary to elevated uric acid [3, 4]. Electrolyte abnormalities may lead to neuromuscular irritability including seizures and cardiac dysrhythmia that can be fatal. Laboratory TLS confers high risk of developing clinical TLS [5].

Several models have been developed for adults with acute myeloid leukemia [6, 7] and children with acute lymphoblastic leukemia [8] to predict the risk of the tumor lysis syndrome. These models lack a standard definition of the tumor lysis syndrome, use different primary end points (i.e., either clinical tumor lysis syndrome or any type of the tumor lysis syndrome), do not have standardized supportive care guidelines, and scoring systems are complex. However, Howard et al. [5] proposed an algorithm for risk stratification depicted here, which suggests escalation of management including intravenous fluids, hypouricemic agents, progressively more frequent laboratory monitoring, and cardiac monitoring, depending on risk to develop clinical TLS.

Patients at high risk for developing tumor lysis syndrome may receive low-intensity initial therapy. The hypothesis is that slower lysis of tumor cells allows renal homeostasis to clear metabolites before their accumulation and subsequent organ damage. In patients with advanced B-cell Non-Hodgkin’s lymphoma and Burkitt’s lymphoma, this approach has involved treatment with low-dose cyclophosphamide, vincristine and prednisone for a week prior to the initiation of intensive chemotherapy. Several groups also subscribe to a week of prednisone monotherapy for childhood acute lymphoblastic leukemia [5].

All patients at risk for, or with, clinical TLS should receive intravenous hydration to optimize glomerular filtration and renal perfusion while maximizing urinary excretion of uric acid and phosphate [9]. Patients at intermediate or high risk for TLS should receive “hyperhydration”, with goal of 4–6 L per day up to 48 h prior to chemotherapy through 72 h following therapy [10]. Some have advocated for up to 3000 ml/m²/day for those at the highest risk [11]. The choice of hydration fluid varies depending upon the clinical circumstances. One expert panel suggests the initial use of 5 % dextrose in one-quarter normal (isotonic) saline [9]. In patients with hyponatremia or volume depletion, isotonic saline should be the initial hydration fluid. As there is a risk of hyperkalemia and hyperphosphatemia with calcium phosphate precipitation once tumor breakdown begins, potassium and calcium should be withheld from the initial hydration fluids. Use of sodium bicarbonate to cause urinary alkalization, while increasing urate excretion, reduces the solubility of calcium phosphate, and is no longer recommended for TLS management, particularly when hypouricemic agents are available [9]. Urinary alkalization has been associated with renal failure in pediatric patients treated with rasburicase [12]. Diuretics may be used to maintain increased urinary flow, though this is controversial (see section “Evidence Contour”).

Reduction of uric acid with allopurinol and rasburicase can preserve or improve renal function [13]. Rasburicase additionally reduces serum phosphate as a secondary benefit. Allopurinol is a xanthine oxidase inhibitor that reduces the formation of uric acid though has no demonstrable effects on the excretion of already formed uric acid. This delay in therapeutic effect can allow urate nephropathy to develop. Furthermore, despite treatment with allopurinol, xanthine can accumulate and this can result in xanthine nephropathy [14, 15]. In a multicenter randomized study of the use of allopurinol versus rasburicase in pediatric patients at risk for TLS, the mean uric acid was significantly decreased in the rasburicase arm in intention to treat analysis. There was also a significant decrease in serum phosphorus, and favorable trends in serum creatinine in patients managed with rasburicase [16]. The serum creatinine level improved by 31 % in the rasburicase group but worsened by 12 % in the allopurinol group. In the study done by Pui et al. [13], there was no increase in phosphorus levels and decrease in creatinine levels among 131 patients who were at high risk for the tumor lysis syndrome and were treated with rasburicase. While either allopurinol or rasburicase may be considered for patients at intermediate risk for development of TLS, rasburicase is advised for a laboratory or clinical diagnosis of TLS [5]. However, Glucose 6 Phosphate Dehydrogenase deficiency is an absolute contraindication to rasburicase, related to risk of hemolysis, and at risk populations should be screened prior to rasburicase initiation if feasible.