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 Table of Contents  
Year : 2013  |  Volume : 4  |  Issue : 3  |  Page : 100-103

Tumor lysis syndrome in children with acute leukemia: Incidence and outcome

1 Department of Pediatrics, Maternity and Children Hospital, AlAhsa, Riyadh, Saudi Arabia
2 Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
3 Department of Nephrology Section, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

Date of Web Publication19-Dec-2013

Correspondence Address:
Muneer Al Bagshi
Department of Pediatrics, Maternity and Children Hospital-Alahsa, 31982 Hofuf-Alahsa Hofuf Eastern 31982
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1658-5127.123304

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Background: Tumor lysis syndrome (TLS) comprises a number of metabolic and renal abnormalities of variable spectrum. It is associated with lymphoproliferative disorder e.g., acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL). The aim of this study to evaluate the incidence, severity and outcome in Saudi children with ALL.
Methods: Medical records of Children age <14 years and diagnosed with ALL were reviewed. We adopted the Hande and Garrow definitions for tumor lysis Syndrome. All patients received hydration, alkalinization with sodium bicarbonate and allopurinol as prophylaxis.
Results: Seventy-four patients developed TLS (19% of all patients). Boys were affected than girls with ratio of 2.4:1. LTLS occurred in 93.3% and CTLS in 6.7%. Hyperphosphatemia was found in 94.6% of the patients. Hyperkalemia occurred only in 17 patients (23%). Hypokalemia was found in significant number of patients (12%). Lymphomatous presentation was seen in 60 patients (82%). Hemodialysis was required in 5 patients (6.6%) and 4 of them had hyperleukocytosis. There were no deaths encounterd due to TLS. Male sex, lymphomatous presentation, high LDH, high pretreatment WBC and central nervous system involvement were found to have statistical significance as risk factors for TLS development.
Conclusion: TLS is a common event in childhood ALL. Spontaneous TLS indicate highly proliferating tumor and possible delayed presentation to our institute. Prophylactic measures are important to improve the outcome particularly when initiated as soon as the diagnosis is established.

Keywords: Acute lymphoblastic leukemia, childhood leukemia, tumor lysis syndrome, Saudi Arabia

How to cite this article:
Al Bagshi M, Sadek A, Hassan E, Abbas A. Tumor lysis syndrome in children with acute leukemia: Incidence and outcome. J Appl Hematol 2013;4:100-3

How to cite this URL:
Al Bagshi M, Sadek A, Hassan E, Abbas A. Tumor lysis syndrome in children with acute leukemia: Incidence and outcome. J Appl Hematol [serial online] 2013 [cited 2023 May 29];4:100-3. Available from: https://www.jahjournal.org/text.asp?2013/4/3/100/123304

  Introduction Top

Tumor lysis syndrome (TLS) comprises metabolic and renal abnormalities, including hyperuricemia, hyperphosphatemia, hyperkalemia, and hypocalcemia with or without acute kidney injury. TLS is associated with malignant lymphoproliferative disorders, especially highly proliferating and chemosensitive tumors, for example, acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). [1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12] However, cases of TLS have been reported in patients with chronic leukemia, solid tumors, and nonmalignant conditions. TLS complications are often subtle, but fatalities have been reported. [13],[14] It can occur because of either prophase or full-induction chemotherapy; [15],[16],[17],[18],[19],[20] however, spontaneous TLS has also been reported. [21],[22] Induction with more intensive chemotherapeutic regimens may increase the incidence and severity of TLS due to the massive break down of malignant cells. Clearance of TLS products occurs primarily through renal mechanisms, and the metabolic derangements associated with TLS can be exacerbated by the development of acute kidney injury. The objectives of this study were to determine the incidence, severity, and outcome of TLS and identify the risk factors for the disease in children with ALL.

  Patients and Methods Top

A retrospective review was conducted of all medical records of patients who were <14 years of age and diagnosed with ALL between January 2000 and December 2005 at King Faisal Specialist Hospital and Research Centre (KFSH and RC), Riyadh, Saudi Arabia.

The diagnosis was confirmed according to the French-American-British (FAB) classification, immunophenotyping, the DNA index, and cytogenetic studies.

Patients who received the initial therapy at the referring hospitals and those who refused therapy were excluded.

We adopted the Hande-Garrow definition for laboratory TLS (LTLS) if two of the following metabolic changes occurred before or within 4 days after the initiation of chemotherapy: 25% increase in serum potassium (K + ), phosphate (PO 4 2+ ), uric acid (UA), and blood urea nitrogen (BUN) levels or a decline in serum calcium (Ca 2+ ). Clinical TLS (CTLS) was defined as LTLS and K + levels >6 mmol/l or acute kidney injury. [20]

All patients initially received intravenous (IV) hydration with dextrose 1/4 saline (3,000 ml/m 2 /day) that was alkalinized with NaHCO 3 ( 40 meq/l) and p.o. allopurinol (10 mg/kg/day). The bicarbonate was then titrated to maintain a urine pH of 7-7.5.

The following parameters were measured in all patients before the initiation of and during chemotherapy: Baseline and differential complete blood counts; renal profile analysis; and levels of electrolytes, UA, PO4 , Ca 2+ , and lactate dehydrogenase (LDH).

All patients underwent cardiac evaluation.


For all children with ALL, we used children-specific cancer protocols for different immunophenotypic subtypes. [19],[20]

All patients received prophylaxis for pneumocystis carinii using cotrimoxazole p.o. 2.5 mg/kg/dose twice daily 3 days per week.

Statistical analysis: Data were analyzed using the Statistical Package for Social Sciences (SPSS) computer program version 13 by SPSS Inc. Chicago, IL. Univariate analysis and Student's t-test for unequal sample sizes were used, and P < 0.05 indicated significance. The data were analyzed by the Oncology Data Unit at KFSH and RC.

  Results Top

There were 398 patients diagnosed with ALL over a 6-year period (January 2000-December 2005), and 74 patients met the criteria of TLS (19%). The patients' characteristics are listed in [Table 1]. There were 52 boys, and the male-to-female ratio was 2.4:1.

Most patients had precursor B-cell ALL (53, 72%), including 12 patients with early pre-B ALL (negative cytoplasmic immunoglobulin) and 41 with pre-B ALL (positive cytoplasmic immunoglobulin). The remaining diseases included B-cell ALL (positive surface immunoglobulin, 5%) and T-cell ALL (CD3- and CD5-positive, 20%).
Table 1: Characteristics of patients with acute lymphoblastic leukemia

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Of interest, 28% of the patients with TLS had CNS leukemia at presentation (P < 0.0001).

Univariate analysis indicated that lymphomatous presentation (massive splenomegaly or lymph node <3 cm) was found in 60 patients (P < 0.00001), and that male sex (P < 0.001) and a high WBC count (>50,000 × 10 3 ) prior to treatment (P < 0.0001) were risk factors for the development of TLS. However, these factors did not remain significant predictors in multivariate analysis, as listed in [Table 2].

LTLS occurred in 69 patients (93%), whereas only five patients (7%) developed CTLS. Spontaneous TLS occurred in 16 patients (21.9%).

Hyperphosphatemia was found in 95% of the patients, but it was not correlated with outcome.
Table 2: Characteristics of patients with or without TLS

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Hypokalemia was observed in nine patients (12%); [Table 3] lists the incidence of renal abnormalities in the group of patients who developed TLS.

TLS therapy: Most of the patients (93%) were treated conservatively with hydration, alkalinization, and allopurinol. Patients with hyperphosphatemia responded to aluminum hydroxide. Renal replacement therapy in the form of hemodialysis was required in five patients (7%), and one patient required continuous venovenous hemofiltration.
Table 3: Renal laboratory abnormalities in all patients with TLS

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Four of these patients had hyperleukocytosis (WBC count > 100,000 × 10 3 ), as shown in [Table 4].
Table 4: Characteristics of five patients with CTLS

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No deaths occurred due to TLS.

  Discussion Top

The survival of children with ALL has improved significantly in recent years, with a cure rate of 80%. [11],[23],[24],[25],[26] However, certain complications related to therapy, including TLS, which may increase the risk of morbidity and mortality, [5],[6],[7]] remain complicated. In our experience, TLS occurs in a high percentage of children with ALL (19%), even prior to chemotherapy (4%).

In this study, hyperphosphatemia was observed in most patients (95%), and all of these patients developed acute kidney injury. Interesting findings included pretreatment hyperphosphatemia, which was observed in 81% of the patients, and spontaneous TLS, as observed by the high incidence of lymphomatous presentation (82%) owing to late referral of patients. In contrast to the usual hyperkalemia in TLS, we observed hypokalemia in significant number of patients (12%). The same observation was seen among those who underwent renal replacement therapy (3/5) despite very high levels of UA, phosphate, and BUN. No such observations have been reported previously, and a prospective study is needed to uncover the etiology of this finding, as this is the only study of TLS in children with ALL in the population of this ethnicity.

Allopurinol prevents the formation of UA, but it does not eliminate circulating UA. The accumulation of xanthine and hypoxanthine in the renal tubules may occur in a manner similar to that of UA, leading to nephropathy and kidney injury. [27],[28],[29],[30]

Urate oxidase has been used in France and Italy for the treatment of TLS with few side effects [31],[32],[33] It converts UA into soluble allantoin, which is readily excretable by the kidneys. [34],[35] This drug has been approved in Europe and USA, and the results are encouraging. [26],[34],[35],[36]

  Conclusion Top

TLS is a frequent phenomenon in childhood ALL and measures such as hydration and alkalinization should be implemented to prevent this complication. The addition of urate oxidase may reduce morbidity and mortality secondary to TLS, as stated in previous studies. [37]

  Acknowledgements Top

All the stated authors contributed in the write up of the manuscript. The authors declare no conflict of interest.

  References Top

1.Holland P, Holland NH. Prevention and management of acute hyperuricemia in childhood leukemia. J Pediatr 1968;72:358-66.  Back to cited text no. 1
2.Arseneau JC, Bagley CM, Anderson T, Canellos GP. Hyperkalemia, a sequel to chemotherapy to Burkitt's lymphoma. Lancet 1973;1:10-4.  Back to cited text no. 2
3.Muggia FM. Hyperkalemia and chemotherapy. Lancet 1973;1:602-3.  Back to cited text no. 3
4.Breicton HD, Anderson TA, Johnson RE, Schein PS. Hyperphosphatemia and Hypocalcemia in Burkitt's lymphoma. Arch Inter Med 1974;135:307-9.  Back to cited text no. 4
5.Lameire N. Acute tumor lysis and the kidney. Neth J Med 1994;45:193-7.  Back to cited text no. 5
6.Harkel ADJ, Holthe JE, Weel MV, Vorst MM. Topical topic (Alkalinisation and tumor lysis syndrome). Med Pediatr Oncol 1998;31:27-8.  Back to cited text no. 6
7.Jones DP, Mahmoud HH, Chesney RW. Tumor lysis syndrome: Pathogenesis and management. Ped Nephrol 1995;9:206-12.  Back to cited text no. 7
8.Fleming DR, Doukas MA. Acute tumor Lysis in hematologic malignancies. Leuk Lymphoma 1992;8:315-8.  Back to cited text no. 8
9.Boccia RV, Longo DL, Lieber ML, Jaffe ES, Fisher RI. Multiple recurrences of acute tumor lysis syndrome in an indolent non-Hodgkin's lymphoma. Cancer 1985;56:2295-7.  Back to cited text no. 9
10.Kedar A, Grow W, Neiberger. Clinical versus laboratory tumor lysis syndrome in children with acute leukemia. Pediatr Hematol Oncol 1995;12:129-34.  Back to cited text no. 10
11.Mika D, Ahmad S, Guruvayoorappan C. Tumour lysis syndrome: Implications for cancer therapy. Asian Pac J Cancer Pre 2012;13:3555-60.  Back to cited text no. 11
12.Locatelli F, Rossi F. Incidence and pathogenesis of tumor lysis syndrome. Contrib Nephrol 2005;147:61-8.  Back to cited text no. 12
13.Bowman WP, Shuster JJ, Cook B, Griffin T, Behm F, Pullen J, et al. Improved survival for children with B-Cell acute lymphocytic leukemia and stage IV small non cleaved-cell lymphoma: A Pediatric Oncology Group Study. J Clin Oncol 1996;14:1254-61.  Back to cited text no. 13
14.Lorigan PC, Woodings PL, Morgenstren GR, Scarffe JH. Tumor lysis syndrome, case report and review of literature. Ann Oncol 1996;7:631-6.  Back to cited text no. 14
15.Benekli M, Savas MC, Savaþ MC, Kadayifçi A, Altundað MK, Tekuzman G, et al . Acute tumor lysis syndrome following intrathecal methotrexate. Leuk Lymphoma 1996;22:361-3.  Back to cited text no. 15
16.Rajagopal S, Lipton JH, Messner HA. Corticosteroid induced tumor lysis syndrome in acute lymphoblastic leukemia. Am J Hematol 1992;41:66-7.  Back to cited text no. 16
17.Loosveld OJ, Schouten HC, Gaillard CA, Blijham GH. Acute tumor lysis in a patient with acute lymphoblastic leukemia after single dose of prednisone. Br J Hematol 1991;77:122-3.  Back to cited text no. 17
18.Fer MF, Bottino GC, Sherwin SA, Hainsworth JD, Abrams PG, Foon KA, et al. Atypical tumor lysis syndrome in a patient with T-cell lymphoma treated with leukocyte interferon. Am J Med 1984;77:953-6.  Back to cited text no. 18
19.Dhingra K, Newcom SR. Acute tumor lysis syndrome in non-Hodgkin lymphoma induced dexamethasone. Am J Hematol 1998;29:115-6.  Back to cited text no. 19
20.Hande KR, Garrow GC. Acute tumor lysis syndrome in patients with high grade non-Hodgkin's lymphoma. Am J Med 1993;94:133-9.  Back to cited text no. 20
21.Gaynon PS, Trigg ME, Heerema NA, Sensel MG, Sather HN, Hammond GD, et al. Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1993-1995. Leukemia 2000;14:2223-33.  Back to cited text no. 21
22.Reama GH, Sposto R, Sensel MG, Lange BJ, Feusner JH, Heerema NA, et al. Treatment outcome and prognostic factors for infants with acute lymphoblastic leukemia treated on two consecutive trials of the Children's Cancer Group. J Clin Oncol 1999;17:438-40.  Back to cited text no. 22
23.Pui CH, Evans W. Acute Lymphoblastic Leukemia. New Engl J Med 1998;339:605-15.  Back to cited text no. 23
24.Levin M, Cho S. Acute tumor lysis syndrome in high grade lymphoblastic lymphoma after a prolonged episode of fever. Med Pediatr Oncol 1996;26:417-8.  Back to cited text no. 24
25.Pui CH. Recent advances in the biology and treatment of childhood acute lymphoblastic leukemia. Curr Opin Oncol 1998;5:292-301.  Back to cited text no. 25
26.Tazi I, Nafl H, Elhoudzi J, Mahmal L, Harif M. Management of pediatric tumor lysis syndrome. Arab J Nephrol Transplant 2011;4:147-54.  Back to cited text no. 26
27.Band PR, Silverberg DS, Henderson JF, Ulan RA, Wensel RH, Banerjee TK, et al. Xanthine Nephropathy in a Patient with Lymphosarcoma treated with Allopurinol. New Engl J Med 1970;283:354-7.  Back to cited text no. 27
28.Albin A, Stephens BG, Hirata T, Wilson K, Williams HE. Nephropathy, xanthinuria, and orotic aciduria complicating Burkitt's lymphoma treated with chemotherapy and allopurinol. Metabolism 1972;21:771-8.  Back to cited text no. 28
29.Greene ML, Fujimoto WY, Seegmiller JE. Urinary xathine stone-a rare complication of allopurinol therapy. New Engl J Med 1969;280:426-7.  Back to cited text no. 29
30.Pinkerton RC, Gerrard M, Hann I, Eden OB, Carter R. United Kingdom Children's Cancer Study Group (UKCCSG): Experience with the French SFOP intensive regimen for advanced B lymphoblastic lymphoma. Proc Int Soc Ped Oncol 1993; 532:A3.  Back to cited text no. 30
31.Masera G, Jankovic M, Zurlo MG, Locasciulli A, Rossi MR, Uderzo C, et al. Urate-oxidase prophylaxis of uric acid induced renal damage in childhood leukemia. J Pediatr 1982;100:152-5.  Back to cited text no. 31
32.Pui CH, Relling MV, Lascombes F, Harrison PL, Struxiano A, Mondesir JM, et al. Urate oxidase in the prevention and treatment of hyperuricemia associated with lymphoid malignancies. Leukemia 1997;11:1813-6.  Back to cited text no. 32
33.Mahmoud HH, Leverger G, Patte C, Harvey E, Lascombes F. Advances in the management of malignancy associated hyperuricemia. Br J Cancer 1993;77 Suppl 4:18-20.  Back to cited text no. 33
34.Wilson FP, Berns JS. Onco-nephrology: Tumor lysis syndrome. Clin J Am Soc Nephrol 2012;7:1730-9.  Back to cited text no. 34
35.Firwana BM, Hasan R, Hasan N, Alahdab F, Alnahhas I, Hasan S, et al. Tumor lysis syndrome: A systematic review of case series and case reports. Postgrad Med 2012;124:92-101.  Back to cited text no. 35
36.Navolanic PM, Pui CH, Larson RA, Bishop MR. Elitek-rasburicase: An effective means to prevent and treat hyperuricemia associated with tumor lysis syndrome, a Meeting Report, Dallas, Texas, January 2002. Leukemia 2003;17:499-514.  Back to cited text no. 36
37.Hagino T. Tumor lysis syndrome (Abstract). Gan To Kagaku Ryoho 2010;37:984-8.  Back to cited text no. 37


  [Table 1], [Table 2], [Table 3], [Table 4]

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