Hypoglycemia associated with L-asparaginase in acute lymphoblastic leukemia treatment: a case report

The enzyme L-asparaginase (L-Asp) has been commonly used for treatment of childhood acute lymphoblastic leukemia (ALL) for more than 30？years [1-3]. Because of its unique pharmacological features and historically improved treatment outcomes, L-Asp forms an essential part of ALL regimens worldwide [4]. However, many adverse effects of L-Asp have been documented, such as coagulopathy, acute pancreatitis, allergic reaction, hyperlipidemia, hyperammonemia, hepatotoxicity, and hyperglycemia [5-8]. Therefore, clinicians must carefully monitor patients treated with L-Asp for these adverse effects. Until date, hypoglycemia has not been formally reported as an adverse effect of L-Asp. We report, for the first time, a case of hypoglycemia associated with L-Asp use.A 5-year-old girl with Philadelphia chromosome-positive ALL was treated with the induction therapy protocol of the Tokyo Children’s Cancer Study Group (TCCSG) L99-15 for high-risk patients. Therapy included prednisolone, vincristine, cyclophosphamide, daunorubicin, triple intrathecal injection, and L-Asp (Kyowa Hakko Kirin, Tokyo, Japan) [9]. The patient was administered 6000？IU/m2 of native Escherichia coli L-Asp on days 16, 18, 20, 23, 25, 27, 30, 32, and 34 of treatment. On day 18, she developed fasting hypoglycemia (glucose, 56？mg/dL) with severe hunger and without other signs or symptoms such as tremor, palpitation, anxiety, sweating, or paresthesias. On day 27 (fasting serum glucose level, 50？mg/dL), critical blood sampling showed 6？U/mL of immunoreactive insulin, 0.47？mEq/L of free fatty acids, and 27？mol/L of ketone bodies. She repeatedly developed fasting hypoglycemia (glucose, 38–65？mg/dL) until day 37, without serious complications (Figure 1). Five days after the last L-Asp administration, her fasting glucose levels were elevated from 73 to 87？mg/dL. During induction therapy, fasting glucose levels were always measured before the morning steroid dose.TCCSG L99-15 intensification-1, including high-dose cyt