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 Table of Contents  
ORIGINAL ARTICLE
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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  Abstract 

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 2018 May 23];4:100-3. Available from: http://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.

Chemotherapy

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

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    Tables

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


This article has been cited by
1 Tumor Lysis Syndrome in Patients with Hematological Malignancies
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Journal of Oncology. 2017; 2017: 1
[Pubmed] | [DOI]



 

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