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Frequency of Tumor Lysis Syndrome in Aggressive and Slow
Introduction Chemotherapy in Children with ALL
Hashemi A 1, Shahvazian N 2, Zarezade A 2, Shakiba M 3, Atefi A 4
1- Department of Pediatrics, Hematology, Oncology and Genetics Research Center, Shahid Sadoughi University of Medical Sciences and
Health Services, Yazd, Iran
2- General Practitioner , Yazd, Iran
3- Department of Pediatrics, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
4- Hematology, Oncology and Genetics Research Center, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd,
Tumor Lysis Syndrome (TLS) is an oncologic emergency that results from massive lysis of
malignant cells. The incidence of TLS depends on the risk factors, such as baseline
hyperuricemia, bulky tumor burden, elevated serum LDH, and elevated WBC. The objectives of
the present study were to assess frequency of Tumor Lysis Syndrom in children with ALL in two
methods of induction chemotherapy, aggressive and slow induction.
Materials and Methods
In this double blind randomized interventional study, the number of 60 ALL patients in the
Shahid Sadoughi Hospital Yazd were studied. They randomly treated using two various
methods; 30 patients by invasive and 30 by slow induction chemotherapy.
From 60 patients, 10 cases (16.6%) developed Tumor lysis syndrome. Seven of 10 treated by
aggressive chemotherapy and remaining 3 by slow chemotherapy. No significant differences
were found (PV= 0.166) between them.
Based on this study there was no significant difference between Tumor Lysis Syndrom in
aggressive induction chemotherapy and slow induction, but WBC and LDH levels before
treatment can predict Tumor Lysis Syndrom.
ALL, Tumor Lysis Syndrome,Induction Chemotherapy
Hashemi A MD. Hematology, Oncology and Genetics Research Center, Shahid Sadoughi University of
Medical Sciences and Health Services, Yazd, Iran Email: [email protected]ahoo.com
Iranian Journal of Pediatric Hematology and Oncology Vol1. No1. Introduction
Tumor Lysis Syndrome (TLS) is an oncologic emergency that results from massive lysis of
rapidly proliferating malignant cells. TLS characterize by hyperuricemia, hyper kalemia and
hyperphosphatemia, which might lead to hypocalcemia with tetanus or other potentially life
threatening complications. Arrhythmias occur as a result of hyperkalemia in 5% of the patients
and are the most common cause of death in TLS. TLS usually develops shortly after the start of
the effective cytotoxic therapy and it may lead to acute renal failure and death. It usually happens
either before or within 1-5 days of after starting specific anti-leukemia therapy (1, 2, 3).
TLS is commonly seen in tumors with a high mitotic rate such as Burkitt lymphoma or T cell
leukemia. It is less common in AML and pre-B-ALL and could occur with CML with the
administration of combined cytotoxic chemotherapy. It is rarely reported after single-agent
corticosteroid therapy (3, 4, 5).
The incidence of TLS is 3% to 22%, which depends on the patients risk factors such as baseline
hyperuricemia, bulky tumor burden (more than 10cm), concentrated acidic urine ph, elevated
serum LDH, elevated WBC (more than 100000/μl), first course chemotherapy in patients with
bulky tumor, hematological malignancies with a high proliferative index, and volume depletion
The prevention of TLS is as important as its diagnosis and management. The regimen of
hydration (2-4 maintenance), alkalinization (to keep urine ph between 7 and 7.5) and allopurinol
prevent clinically significant TLS (3).
Allopurinol could treat hyperuricemia of malignancy, but is associated with drawbacks.
Rasburicase which recently become available in the united stats, provides a safe and effective
alternative to allopurinol. It decreases uric acid levels and prevents uric acid nephropathy (1).
ALL is a heterogeneous disease has led to treatment directed according to phenotype, genotype,
and risk. Thus, mature B cell ALL is the only subtype that is treated with short-term intensive
chemotherapy (7, 8).
The goal of induction therapy is to eradicate more than 99 percent of the initial burden of
leukemia cells, restore normal hematopoiesis, and a normal performance status. This treatment
phase almost always includes the administration of a glucocorticoid (prednisone, prednisolone,
or dexamethasone), vincristine, and at least one other agent (usually asparaginase, an
anthracycline, or both). Children and nearly all young adults with high-risk ALL receive four or
more drugs during induction therapy. Overly aggressive induction therapy might lead to
increased morbidity and mortality (9, 10, 11).
Dexamethasone has good penetration into the central nervous system with long half-life, which
provides better control in the central nervous system than prednisone or prednisolone (12, 13).
The objectives of the present study were to asses frequency of Tumor Lysis Syndrom in children
with ALL in two methods of induction chemotherapy, aggressive and slow induction.
Materials and Methods
In this double blind randomized interventional study, the number of 60 ALL patients from 2007
until the end of 2008 in the Shahid Sadoughi Hospital Yazd were studied. They randomly
allocated in two groups, which one group had invasive chemotherapy and other group slow
induction. The patients included 36(60%) boys and 24(40%) girls aged between 1 to 10 years old
(Average 6 years old).
Iranian Journal of Pediatric Hematology and Oncology Vol1. No1. In this study laboratory finding in patients before chemotherapy and 48 and 72 hours after
chemotherapy was assessed. They included potassium, calcium, phosphorus, uric acid, urea,
creatinine, alkalinphosphatas, LDH, and WBC.
Statistical methods included Fisher exact and Chi square were analyzed the findings.
From 60 patients, 10 cases (16.6%) developed Tumor lysis syndrome, which 7(23%) received
aggressive chemotherapy and 3 (10%) slow chemotherapy. No significant differences were
found (PV=0.166) between them (table1).
Table1: Frequency of TLS in the two groups of patients
Number Percent Number Percent Number Percent
These was no significant relation between sex and age of patients with TLS (PV>0.05).
Table2: Frequency of TLS in WBC and LDH groups
Number Percent Number Percent Number Percent The relationship between LDH and WBC before treatment with TLS, were significant (LDH
=PV: 0.005, WBC= PV: 0.023) in this table.
Based on this study there was no significant difference between TLS in aggressive induction
chemotherapy and slow introduction, and WBC and LDH levels before treatment could predict
The acute tumor lysis syndrome has been reported most commonly after combination
chemotherapy, all in patients with non-Hodgkin‘s lymphoma. Dhingra an Newcom (1988)
described an acute tumor lysis syndrome. Single agent corticosteroid treatment in a patient with
non-Hodgkin's lymphoma caused renal failure 72 h after dexamethasone therapy. Sparano et al
(1990) described a patient developing life threatening hyperkalaemia within 12 h after 100 mg
dexametasone. Acute tumor lysis syndrome occurs rarely after single agent corticosteroid
therapy, but scientists believe that prescribing corticosteroids for patients with bulky disease
Iranian Journal of Pediatric Hematology and Oncology Vol1. No1. non-Hodgkin's lymphoma or leukaemia should be aware of this potentially life-threatening
complication and monitor the patient very closely (14).
One study suggested that an increased dose of prednisolone in the context of other intensive
treatment can yield results similar to those achieved with dexamethasone (15). Imatinib
mesylate, a tyrosine kinase inhibitor, has enhanced the management of leukemia with BCR-ABL
fusion, especially in elderly adults. Imatinib either as a single agent or as part of combination
regimens has successfully induced or consolidated remissions (16, 17). However, its capacity to
improve the cure rate remains uncertain. It has clearly contributed to extend disease-free survival
and improve quality of life among these patients.
The incidence of TLS can range from 3% to 22% such as Bulky tumor burden (>10cm), elevated
WBC (leukemia) and elevated LDH (5, 6).
Kapoor et al defined 22% of ALL cases and 15% AML cases presented with hyperleucocytosis.
They reported WBC level before treatment can predict tumor lysis syndrome(3). This is
concordance with present studies. However, limited study was reported.
Michael B.Davidson et al described the metabolic and electrolyte disturbances of tumor lysis
syndrome may be concurrently exacerbated by renal failure. Patients may be treated with
Allopurinol, hydration, urinary alkalinization, or hemodialysis. Rasburicase was recently
approved in the United States, and may be more effective than allopurinol (1).
One randomized study demonstrated more rapid control and lower levels of plasma uric acid in
patients who received rasburicase compared to allopurinol that is effective alternative to
allopurinol during chemotherapy (18).
Prevention of TLS is to identify patients at risk and follow them clearly by testing those 48 hours
after chemotherapy. The first step in prevention of TLS is to minimize the risk factors during the
high risk period, which starts from 3 days before to 7 days after chemotherapy (5).
In conclusion, based on this study there was no significant difference between tumor lysis
syndrom in aggressive induction and slow induction chemotherapy, but WBC and LDH levels
before treatment could predict tumor lysis syndrom.
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Detection, Occurrence, and Fate of Emerging Contaminants in Agricultural Environments Daniel D. Snow1, Shannon L. Bartelt-Hunt2, Samuel E. Saunders3 and David A. Cassada4 ‘Emerging' contaminants are any synthetic or steroid hormones and other endocrine-disrupting naturally-occurring chemical or microorganism not commonly monitored in the environment. These "new"