JOURNAL CLUB

Presented by-

Dr. Md. Tanvir Ahammed

MD (Phase-B) Resident
Pediatric Hematology & Oncology

Date: 22-06-2016
TITLE:

Glucose Levels Before the Onset of Asparaginase Predicts

Transient Hyperglycemia in Children With Acute
Lymphoblastic Leukemia
 Glucose Levels Before the Onset of Asparaginase
Predicts Transient Hyperglycemia in Children With
Acute Lymphoblastic Leukemia
Pediatr Blood Cancer 2016; 63: 1181 – 1184

Received 12 January 2016; Accepted 1 February 2016, Published online 8 April 2016 in Wiley Online
Library
AUTHOR:

Irene Gatzioura, Eugene Papakonstantinou, Meropi Dimitriadou, Maria

Kourti, Vassiliki Sidi, Panagiota Triantafyllou, Dimitrios Koliouskas and
Athanasios Christoforidis
Introduction:

• Hyperglycemia constitutes an acknowledged adverse event that occurs during treatment in children with acute lymphoblastic
leukemia (ALL) and is mainly attributed to the administration of corticosteroids in combination with asparaginase.
• This phenomenon usually appears early in the course of ALL
treatment (induction phase), when these agents are administered
at high doses.
• Rarely, the initiation of hyperglycemia can be acute, presenting as diabetic ketoacidosis or nonketotic hyperglycemic
hyperosmolar syndrome. Although in approximately half of the cases insulin administration is required, in its vast majority the
phenomenon resolves with the discont inuation of steroids and asparaginase, thus it is refered as “transient hyperglycemia
(TH).”
• However, beyond its benign nature, TH has been associated with poorer relapse-free
survival, poorer overall survival rates, and increased risk for developing metabolic
disturbances in future life.

• The incidence of TH among children treated for ALL has

been reported to vary between 4 and 27.5%. Particularly age >10 years, increased body
weight, family history of diabetes, and Down syndrome have been identified as risk
factors for developing TH in the course of ALL. On the other hand, the use of pegylated L-
Aspa (PEG asparaginase) in contrast to native l-asparaginase has been associated with a
lower incidence of TH. However, the use of
PEG-asparaginase is limited due to its higher cost.
Objective:

• To estimate the incidence of TH among Greek children treated with high doses of corticosteroids and
asparaginase during the induction phase of ALL treatment.

• To identify risk factors for developing TH, especially risk factors that are present early in the course of ALL
treatment thus serving as markers for identifying candidates for prevention interventions.
Methodology:

Study Design:
Retrospective study

Study Population:
102 eligible patients.

Place of The Study:

• Pediatric Oncology Department, Ippokration Hospital, Thessaloniki, Greece
• 1st Pediatric Department, Aristotle University of
Thessaloniki, Greece

Study period:
January 2004 until April 2015.
Inclusion criteria:

• All patients diagnosed with ALL and treated with induction

treatment.
Conclusions:

• The rate of TH developed in this cohort ( 15.68%).

• In few studies it had been shown that, TH during ALL treatment has been associated with increased
infection rates and worse relapse-free and overall survival rates. So TH in the course of ALL
treatment should be prevented if possible. Thus, increased fasting glucose before the initiation of
asparaginase (eighthday of treatment) as proposed by this study could serve as an early marker for
intervention strategies that will prevent the development of such an adverse event .
Limitation:

• Small cohort size.

• Retrospective in nature.
Cross Reference:
1. Stefanie R. Lowas, Daniel Marks and Suman Malempati.
Prevalence of Transient Hyperglycemia During Induction
Chemotherapy for Pediatric Acute Lymphoblastic Leukemia.

Pediatr Blood Cancer 2009;52:814–818.

• Results:
One hundred sixty-two subjects (70 female) were reviewed, 33
(20.4%) of whom had TH. 42.2% of subjects over age 10 years had TH,
compared to 12.0% of younger children (P < 0.001). No gender
difference was found. Overweight (BMI ≥ 95th percentile) and at risk
for overweight (BMI ≥ 85th percentile) were significant risk factors for
TH (P=0.007 and P =0.003, respectively). Native L-asparaginase was
associated with increased TH compared to PEG-asparaginase (P=0.047).