ESPE Abstracts

Introduction: 6 Mercaptopurine (6MP) is a cornerstone of maintenance therapy in pediatric acute lymphoblastic leukemia (ALL). Fasting hypoglycemia is a rare side effect of 6MP therapy that has been observed in children being treated for ALL. We present two pediatric patients who developed symptomatic, fasting hypoglycemia during maintenance therapy.

Case Description: A 7-year-old male with standard risk B ALL receiving maintenance therapy presented after an overnight fast with lethargy, slurred speech, and emesis and was found to have a serum glucose of 24 mg/dl. Symptomatic hypoglycemia resolved after infusion of D10W. The patient had been receiving escalating doses of 6MP and methotrexate in an attempt to achieve adequate myelosuppression over the preceding months, and had been complaining of intermittent nausea and vomiting. 6-Thioguanine nucleotide (6TG) was measured at 298 pmol/8x 10E8 RBCs and 6-methylmercaptopurine (6MMP) 33,100 pmol/8x 10E8 RBCs. An 8-year-old male with relapsed B ALL in second remission receiving maintenance therapy presented after an overnight fast with lethargy, weakness and diaphoresis and was found to have a serum glucose of 39. Symptomatic hypoglycemia resolved after infusion of D10W. The patient also had symptoms of an upper respiratory infection and was found to be infected with rhino/enterovirus. 6TG was measured at 182 pmol/8x 10E8 RBCs and 6MMP 21,051 pmol/8x 10E8 RBCs. Both patients underwent a diagnostic fast, during which no further episodes of hypoglycemia were noted, making a primary endocrinological disorder unlikely as the cause of their hypoglycemia. Thyroid studies were normal. Both patients had markedly elevated 6MMP levels.

Discussion: 6MP is metabolized to 6TG which is myelosuppressive and reduces the risk of re-emergence of the leukemic clone, and 6MMP which can increase the risk for hepatotoxicity and hypoglycemia. Although the exact mechanism remains unknown, it is theorized that elevated 6MMP levels disrupt the conversion of alanine to pyruvate in the liver, consequently impairing gluconeogenesis. 6MMP levels >5700 pmol/8x10E8 RBCs are associated with hepatotoxicity. Strategies to mitigate this unusual side effect include modifications of 6MP administration such as morning or twice daily administration, or adding allopurinol to decrease the formation of 6MMP and increase the formation of 6TG.

Conclusion: Fasting symptomatic hypoglycemia may occur in pediatric patients receiving 6MP. While uncommon, 6MP related hepatotoxicity may lead to pauses in chemotherapy and limit the tolerated doses of 6MP thereby increasing the risk for relapse. Evidence-based strategies which lessen 6MP associated toxicities during maintenance therapy for ALL are needed.