Hypoglycemia and glycemic variability among children with acute lymphoblastic leukemia during maintenance therapy

Abstract

Symptomatic, chemotherapy-related hypoglycemia is a rare complication associated with the administration of purine analogs. The aim of the study was to evaluate 24 h glucose variability and frequency of hypoglycemia among patients with acute lymphoblastic leukemia (ALL) during maintenance therapy (MT). Eighteen children with ALL underwent continuous glucose monitoring (CGM). The number of episodes of hypoglycemia and glucose variability were analyzed. Serum alanine aminotransferase, asparagine aminotransferase, and γ-glutamyl transferase levels were measured as liver function markers. The mean glucose level in CGM equaled 105 ± 13 mg/dL, with standard deviation (SD) 13.8 ± 6.1 mg/dL, and the mean amplitude of glycemic excursions (MAGE) equaled 44.7 ± 19.9 mg/dL. Eight patients had at least one measurement below 70 mg/dL while four patients had measurements below 50 mg/dL. Children with hypoglycemia in CGM examination had a lower median body mass index standard deviation score (BMI Z-score) (-0.65 [-0.94 to -0.27] vs. -0.14 [-0.29 to 0.35]; p = 0.05) and shorter duration of MT (6.5 [4-15] vs. 22.5 [16.5-28] weeks; p = 0.004). Glucose variability parameters were strongly correlated with BMI Z-score and liver function enzymes. Hypoglycemia, particularly at night-time, may develop as a complication of MT in children with ALL. The risk factors for low glucose level are low BMI Z-score and initiation of MT.

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

“…It may reflect lowered plasma levels of the gluconeogenic amino acids (alanine and glutamine) as well as impaired glycogenolysis or glyconeogenesis 119, 121 .…”

Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia

“…Hypoglycemic episodes during fasting157–160 have been associated with high levels of methylated 6MP metabolites 161. It can be counteracted by evening meals with slowly absorbed carbohydrates, by administration of rapidly absorbed carbohydrates (eg, apple juice) in case of symptoms, or by shifting to morning dosage.…”

Incidence and risk factors for hypoglycemia during maintenance chemotherapy in pediatric acute lymphoblastic leukemia

“…13,28,29 Methods to decrease 6-MMP levels, including changing 6-MP dosage or timing of administration and coadministration of allopurinol-which shunts 6-MP metabolism away from production of 6-MMP and toward formation of the antileukemic Although lower BMI has been proposed as a driving factor for hypoglycemia, this hypothesized association has not been consistently demonstrated. 7,9 We also did not identify an association between BMI and hypoglycemia. BMI was assessed as both a continuous and categorical variable, to account for a possible nonlinear relationship.…”

“…2,3 Fasting hypoglycemia associated with maintenance chemotherapy is increasingly described in this population. [4][5][6][7][8][9][10][11] This adverse event is of particular importance, as children with ALL are routinely fasted for therapeutic and monitoring procedures.…”

“…There have been several investigations documenting hypoglycemia during maintenance chemotherapy. [4][5][6][7][8][9][10][11][12][13] Reported rates of this adverse event vary considerably between studies ranging from 7% to as high as 54%. 7,11 While younger age, particularly age ≤6 years, has been consistently reported as a risk factor, other possible risk factors have not clearly emerged.…”