ESPE Abstracts

Background: Acute Lymphoblastic Leukemia (ALL) is the most common pediatric oncologic disease. Nowadays, ALL has become a treatable disease due to a well designed chemotherapy protocol. L-Asparaginase is an essential drug which has improved the long term outcome of ALL. However, hyperglycemia due to L-Asparaginase (4-20%) and PEG- Asparaginase (4-17%) is one side effect and can lead to diabetes mellitus or even to diabetic ketoacidosis DKA (0.8%) in combination with glucocorticoids. Hyperglycemia is usually reversible after stopping this agent.

Case: We report a 12-year-old female presenting to the emergency room with severe abdominal pain, polyuria, polydipsia, lethargy, dehydration, tachycardia, and Kussmaul respiration. Laboratory studies showed glycemia: 845 mg/dl, Na: 126mEq/l, K: 5.4mEq/l, Cl: 86mEq/l, HCO3: 4mEq/l, HbA1c: 7.5% with normal pancreatic enzymes. Few months prior to hospitalization, she was diagnosed with T-cell ALL and began treatment with Total 15 Protocol. After her 4^th dose of L-Asparaginase, her physician changed to PEG-Asparaginase due to hyperglycemia. After her third dose of PEG-Asparaginase, she developed severe DKA and was treated with intravenous normal saline and rapid insulin at a rate of 0.1u/kg/h and was shifted to basal-bolus regimen for the remaining period of therapy then she recovered from her diabetes and ALL.

Discussion: Asparaginase is one of the main stay treatments of ALL. Hyperglycemia is a well known complication ranging from 2.5-23% in pediatric population which is due to decreased insulin secretion, increased insulin resistance or excess glucagon formation. Asparaginase decreases insulin secretion by depleting the 3 Asparagine molecules composing the insulin structure. Asparaginase could cause direct beta cell damage due to acute pancreatitis leading to decreased insulin secretion. Increased insulin resistance could be caused by alteration in function of insulin receptors. Concomitant corticosteroids therapy could worsen the glycemic disorder. The elevation of HbA1c reveals a glycemic disorder having started few months prior to presentation. Age over 10 year-old and obesity are significant risk factors for the development of DKA.

Conclusion: Physicians treating children with ALL should be aware of the possibility of hyperglycemia, diabetes mellitus, and DKA due to L-Asparaginase in combination with glucocorticoids and should inform and teach parents about this potential complication. Monitoring of glycemia by a glucometer is essential for screening hyperglycemia post-Asparaginase and glucocorticoids. In case of hyperglycemia, or elevation of HbA1c, we should start insulin treatment to decrease the risk of DKA without any alteration in the treatment protocol since hyperglycemia should resolve after chemotherapy.