Tumor lysis syndrome (TLS) is an acute, life-threatening condition that occurs either spontaneously or as a complication of cytoreductive antitumor therapy, and occurs in both children and adults. As a result of TLS, intracellular components are released into the extracellular space, leading to dysregulation of the body's homeostasis due to the accumulation of uric acid, phosphate and potassium ions, and hypocalcemia, which may lead to cardiac arrhythmias, convulsions, or kidney failure

Niedobylski, Sylwiusz

Piwoński, Michał

Stanicki, Paweł

Żak, Klaudia

English

Akademicka Platforma Czasopism

215Piwoński Michał, Żak Klaudia, Niedobylski Sylwiusz, Stanicki Paweł. Prevention, diagnosis and treatment of tumor lysis syndrome.Journal of Education, Health and Sport. 2021;11(9):215-222. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2021.11.09.027https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2021.11.09.027https://zenodo.org/record/5512498The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019.© The Authors 2021;This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, PolandOpen Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium,provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike.(http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited.The authors declare that there is no conflict of interests regarding the publication of this paper.Received: 01.09.2021. Revised: 12.09.2021. Accepted: 15.09.2021.Prevention, diagnosis and treatment of tumor lysis syndromeMichał Piwoński (1), Klaudia Żak (1), Sylwiusz Niedobylski (1), Paweł Stanicki (1)(1) Students’ Scientific Group at the Department of Applied Psychology, MedicalUniversity of LublinMichał Piwoński, ORCID: 0000-0001-6510-8993, michalpiwonski2@gmail.comKlaudia Żak, ORCID: 0000-0003-2421- 2553, zakklaudia3@gmail.comSylwiusz Niedobylski, ORCID: 0000-0001-7266-623X, sniedobylski@gmail.comPaweł Stanicki, ORCID: 0000-0002-4942-9030, stanicki99@gmail.comAbstractTumor lysis syndrome (TLS) is an acute, life-threatening condition that occurs eitherspontaneously or as a complication of cytoreductive antitumor therapy, and occurs in bothchildren and adults. As a result of TLS, intracellular components are released into theextracellular space, leading to dysregulation of the body's homeostasis due to theaccumulation of uric acid, phosphate and potassium ions, and hypocalcaemia, which maylead to cardiac arrhythmias, convulsions or kidney failure.Key words: tumor lysis syndrome; prevention; treatment; chemotherapy216IntroductionTumor lysis syndrome (TLS) is a metabolic disorder that occurs as a result of therapid breakdown of cancer cells due to chemotherapy or radiotherapy. As a result,intracellular components are released into the extracellular spaces, which can result in life-threatening metabolic disorders [1,2]. Most often, the tumor lysis syndrome refers toneoplasms characterized by high chemosensitivity, high proliferation index and high cellmass. It is worth mentioning that, according to studies, acute tumor lysis syndrome may leadto the formation of embolic materials consisting of nuclear and cytoplasmic debris, whichresults in mechanical obstruction of the vascular bed [3,4].The Cairo-Bishop criteria are used to identify and diagnose clinical tumor lysissyndrome (CTLS), taking into account the level of creatinine, the presence and type ofarrhythmia, and the presence and severity of neurological disorders (seizures) [5,6]. In orderto confirm the CTLS, it is necessary to confirm one of the above-mentioned criteria and atleast two of the following laboratory exponents:● serum uric acid level ≥8 mg/dL, or a 25% increase from baseline;● serum potassium level ≥6 mmol/L, or a 25% increase from baseline;● serum phosphate levels ≥6.5 mg/dL in children and ≥4.5 mg/dL in adults, or a 25%increase from baseline;● serum calcium level ≤7 mg/dL, or a 25% decrease from baseline.If the clinical criteria are not met and at least two laboratory criteria are met, the diagnosis islatent tumor lysis syndrome (LTLS). Importantly, the above-mentioned disorders must occurwithin 3 days before or up to 7 days after the start of chemotherapy [5].Tab. 1 Cairo-Bishop criteria for diagnosis of TLS [5].Laboratory criteria Clinical criteriaUric acid ≥8,0 mg/dL or 25% increase ● Creatinine 1,5 timesthe upper limit ofnormal● Cardiac arrhythmias● SeizuresPotassium ≥6,0 mmol/l or 25% increasePhosphorus ≥4,6 mg/dL or 25% increaseCalcium ≤7,0 mg/dL or 25% increase217Risk factors and the most common complicationsTumor lysis syndrome (TLS) is a complication of chemotherapy for several differenttypes of cancer. It is most common in response to the treatment of hematopoieticmalignancies, but there are also reports of TLS in people with solid tumors: small cellcarcinoma, breast cancer, germ cell tumor, neuroblastoma or melanoma [7]. The risk factorsin those cases are the presence of high tumor burden, metastases [8] as well as high tumoradvancement and high sensitivity to therapy [9]. Tumor lysis syndrome is typically seen inpatients with non-Hodgkin lymphoma (NHL) - especially Burkitt's lymphoma, acutelymphoblastic leukemia and acute myeloid leukemia (AML). TLS is found in 42% of NHLpatients, with up to 6.1% developing clinically significant derangements. In the case of AMLchemotherapy, the tumor lysis syndrome is present in approximately 17% of patients - 5%develop clinically significant complications [10].In addition to the presence of abnormal haematological hyperplasia, there are alsoother risk factors for TLS. An analysis by Truong et al. Indicated: age ≥10 years (P <0.0001),splenomegaly (P <0.0001), mediastinal mass (P <0.0001) and initial WBC ≥20 x 109 / L (P<0, 0001) as independent TLS predictors. In the absence of any of these factors, the TLSnegative prediction factor was 97%, with a sensitivity of 95% [11]. In addition, a number ofother factors not directly related to the cancer and its advancement predispose to thedevelopment of the tumor lysis syndrome. Dehydrated patients with oliguria or anuria andpreexisting renal dysfunction have a higher risk of developing electrolyte disturbances andacute kidney injury in TLS [10]. Similarly, pre-existing electrolyte disturbances(hyperuricemia, increased uric acid concentration) significantly contribute to the developmentof TLS [9].According to the definition, the symptoms of tumor lysis syndrome occur up to 7 daysafter the initiation of cancer therapy [10], but most often they are observed 12-72 hours afteradministration of cytolytic chemotherapy [12]. As a result of the breakdown of cancer cells,significant amounts of potassium, uric acid and phosphorus are released into the bloodstream.The excess of these substances is normally excreted by the kidneys, but in the case of TSL,the hyperkalemia, hyperuricemia and hyperphosphatemia are too great to be compensated byrenal filtration. Uric acid overload leads to its precipitation in the renal tubules and thedeposition of crystals in collecting tubules and ureters, which results in acute renal failure(AKI) [13]. The development of AKI is also favored by the deposition of calcium andphosphate crystals in kidneys and by crystallizing xanthine [13]. Rapid changes in potassiumlevels are also very dangerous. Hyperkalemia in TLS leads to ventricular arrhythmias, which218may lead to cardiac arrest and even death [9,12]. The hypocalcaemia that occurs in TLS ismost often secondary to phosphorus chelation. Calcium deficiency exacerbates thearrhythmia caused by hypokalaemia. It also leads to the development of tetany (calciumdeficiency in muscles, inability to relaxate) and, in more advanced stages, seizures and death[14]. Low calcium levels may persist even after normalization of phosphorus levels due tovitamin D deficiency - often present in patients with cancer [14,15].Methods of preventionIn patients at high or moderate risk of developing TLS, the importance of repeatedmonitoring of laboratory parameters at least twice a day, both before and 7 days afterantitumor therapy, is indicated. Additionally, strenuous hydration and meticulous analysis offluid balance (in order to maintain diuresis> 100mL / h) are the key to proper preventivemanagement. The role of hydration in increasing renal tubular flow and promoting theelimination of urate and phosphate is indicated. Elderly patients or those suffering from heartfailure should be given special care. If the desired diuresis cannot be achieved, it is advisableto use loop diuretics. One should remember about the interactions of thiazide diuretics withallopurinol and their influence on the level of uric acid, therefore their use in the preventionof TLS is not recommended [16–18].Another important step in the prevention of TLS is the administration ofhypouricemic agents, such as allopurinol or rasburicase. It should be remembered thatallopurinol has no properties that reduce uric acid concentration before the initiation oftreatment, therefore rasburicase is used in patients with pre-existing hyperuricemia.Prophylaxis of allopurinol should be induced in patients at moderate and high risk of TLS,and its use should be considered in patients at low risk. Prophylaxis with allopurinol shouldbe performed up to three days before the start of chemotherapy [17,19].It is also worth paying attention to urine alkalinization as a method historicallyrecommended in therapeutic and preventive management. Nevertheless, evidence gathered inrecent years has shown an impact of this approach on the accumulation of calcium phosphatein the renal tubules, particularly in hyperphosphatemia patients. Hence, urine alkalinization isnot used in the prophylaxis or treatment of TLS [17].TreatmentThe most important elements of the treatment of clinically overt TLS is managementof the life-threatening conditions, which consist of renal failure, arrhythmia and seizure, as219well as abnormalities causing them. The therapeutic approach differs – among other factors -depending on the current glomerular filtration rate. While intensive hydration in combinationwith diuretics might still be considered a prevention strategy, a total renal failure is usually asign of a fully developed syndrome [20]. Although the indications for haemodialysis are thesame as for other causes of renal failure in TLS, some authors suggest higher thresholds dueto the possibility of more efficient normalization of the ions levels [5]. Continuous veno-venous hemofiltration was found to be safe and effective treatment even for paediatricpatients with TLS [21]. Due to the occlusive nature of renal failure in TLS it’s important tolimit the crystallisation of uric acid in kidneys by either limiting its production withallopurinol or rasburicase, or inhibiting the crystallisation process itself [20]. Althoughallopurinol is more widely used, more and more evidence emerges on the superiority ofrasburicase. A 2013 meta-analysis showed that single-dose rasburicase as well as dailydosing of rasburicase were significantly more efficient at lowering the uric acid levels in highTLS risk individuals [22]. The strategy of inhibiting the crystallisation of uric acid in kidneysremains controversial and is not routinely recommended, although the urine alkalinisationwith the use of acetazolamide or sodium bicarbonate showed the ability of increasing the uricacid solubility [23].The most dangerous abnormality in electrolyte levels is hyperkalemia, due to highrisk of life-threatening arrhythmia. The temporary, yet very effective strategy to lower thepotassium blood levels is IV injection of insulin and dextrose, which cause the shift ofextracellular potassium into the cells. Hyperkalemia can be managed by administration ofsodium polystyrene sulfonate as well. Extremely high levels of potassium can be reduced bydialysis, if necessary [24].Seizures in TLS are caused by severe hyperphosphatemia and rapidly progressinghypocalcemia. Initial treatment of hyperphosphatemia usually includes extensive hydration,although phosphate binders such as aluminum hydroxide are utilised as well. Dialysis is aneffective phosphate lowering factor as well [20]. Although hypocalcemia can often remainasymptomatic, infusion of calcium gluconate may be considered (only in justified cases, dueto the risk of calcium-phosphate renal precipitation [5].SummaryTLS is an example of an acute condition often present in cancer patients. Whenintracellular components are released into the extracellular space, the body's compensatorycapacity is exceeded, leading to kidney and heart disorders, leading to their failure due to220excessive electrolyte concentrations. Hence, when planning anti-cancer therapy, attentionshould be paid to the risk of TLS in a given patient in order to implement appropriateprophylaxis or treatment. Preventive treatment is based on rehydration of the patient,monitoring of his vital functions and, if necessary, administration of hypoureximizingsubstances. Treatment in the event of overt or laboratory-confirmed TLS is based on restoringthe concentrations of electrolytes and uric acid to physiological levels, controllingarrhythmias, seizures or conducting renal replacement therapy. Undoubtedly, due to the agingof the population, TLS will become an increasingly common problem. Thus, the key is thecooperation of healthcare professionals at every stage of anti-cancer treatment.Bibliography1. Howard SC, Jones DP, Pui C-H. The tumor lysis syndrome. N Engl J Med. 2011 May12;364(19):1844–54.2. Abu-Alfa AK, Younes A. Tumor lysis syndrome and acute kidney injury: evaluation,prevention, and management. Am J Kidney Dis Off J Natl Kidney Found. 2010 May;55(5Suppl 3):S1-13; quiz S14-19.3. Vogel P, Pletcher JM, Liang Y. Spontaneous acute tumor lysis syndrome as a cause ofearly deaths in short-term carcinogenicity studies using p53 +/- mice. Vet Pathol. 2010Jul;47(4):719–24.4. Mirrakhimov AE, Voore P, Khan M, Ali AM. Tumor lysis syndrome: A clinical review.World J Crit Care Med. 2015 May 4;4(2):130–8.5. Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies andclassification. Br J Haematol. 2004 Oct;127(1):3–11.6. Lam AQ, Humphreys BD. Onco-nephrology: AKI in the cancer patient. Clin J Am SocNephrol CJASN. 2012 Oct;7(10):1692–700.7. Williams SM, Killeen AA. Tumor Lysis Syndrome. Arch Pathol Lab Med. 2019Mar;143(3):386–93.8. Baeksgaard L, Sørensen JB. Acute tumor lysis syndrome in solid tumors--a case reportand review of the literature. Cancer Chemother Pharmacol. 2003 Mar;51(3):187–92.9. Burns RA, Topoz I, Reynolds SL. Tumor lysis syndrome: risk factors, diagnosis, andmanagement. Pediatr Emerg Care. 2014 Aug;30(8):571–6; quiz 577–9.10. Truong TH, Beyene J, Hitzler J, Abla O, Maloney AM, Weitzman S, et al. Features atpresentation predict children with acute lymphoblastic leukemia at low risk for tumorlysis syndrome. Cancer. 2007 Oct 15;110(8):1832–9.22111. Cairo MS, Coiffier B, Reiter A, Younes A, TLS Expert Panel. Recommendations for theevaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and childrenwith malignant diseases: an expert TLS panel consensus. Br J Haematol. 2010May;149(4):578–86.12. Del Toro G, Morris E, Cairo MS. Tumor lysis syndrome: pathophysiology, definition,and alternative treatment approaches. Clin Adv Hematol Oncol HO. 2005 Jan;3(1):54–61.13. Cheung WL, Hon KL, Fung CM, Leung AK. Tumor lysis syndrome in childhoodmalignancies. Drugs Context. 2020;9:2019-8–2.14. Adeyinka A, Bashir K. Tumor Lysis Syndrome. In: StatPearls [Internet]. Treasure Island(FL): StatPearls Publishing; 2021 [cited 2021 Sep 12]. Available from:http://www.ncbi.nlm.nih.gov/books/NBK518985/15. Jackmann N, Mäkitie O, Harila-Saari A, Gustafsson J, Nezirevic Dernroth D, Frisk P.Vitamin D status in children with leukemia, its predictors, and association with outcome.Pediatr Blood Cancer. 2020 Apr;67(4):e28163.16. Coiffier B, Altman A, Pui C-H, Younes A, Cairo MS. Guidelines for the Management ofPediatric and Adult Tumor Lysis Syndrome: An Evidence-Based Review. J Clin Oncol.2008 Jun 1;26(16):2767–78.17. Jones GL, Will A, Jackson GH, Webb NJA, Rule S, British Committee for Standards inHaematology. Guidelines for the management of tumour lysis syndrome in adults andchildren with haematological malignancies on behalf of the British Committee forStandards in Haematology. Br J Haematol. 2015 Jun;169(5):661–71.18. McCurdy MT, Shanholtz CB. Oncologic emergencies. Crit Care Med. 2012Jul;40(7):2212–22.19. Kennedy LD, Koontz S, Rao K. Emerging role of rasburicase in the management ofincreased plasma uric acid levels in patients with hematologic malignancies. J Blood Med.2011;2:1–6.20. Criscuolo M, Fianchi L, Dragonetti G, Pagano L. Tumor lysis syndrome: review ofpathogenesis, risk factors and management of a medical emergency. Expert Rev Hematol.2016;9(2):197–208.21. Wang Y, Lu J, Tao Y. Impact of daytime continuous veno-venous haemofiltration ontreatment of paediatric tumour lysis syndrome. J Int Med Res. 2018 Sep;46(9):3613–20.22. Feng X, Dong K, Pham D, Pence S, Inciardi J, Bhutada NS. Efficacy and cost of single-dose rasburicase in prevention and treatment of adult tumour lysis syndrome: a meta-analysis. J Clin Pharm Ther. 2013 Aug;38(4):301–8.22223. Jones DP, Mahmoud H, Chesney RW. Tumor lysis syndrome: pathogenesis andmanagement. Pediatr Nephrol Berl Ger. 1995 Apr;9(2):206–12.24. Sarno J. Prevention and management of tumor lysis syndrome in adults with malignancy.J Adv Pract Oncol. 2013 Mar;4(2):101–6.

Prevention, diagnosis and treatment of tumor lysis syndrome

https://apcz.umk.pl/JEHS/article/download/35226/29729

Prevention, diagnosis and treatment of tumor lysis syndrome

Abstract

Similar works

Full text

Available Versions

Akademicka Platforma Czasopism