Hyperglycemia among children below 18 years with acute lymphoblastic leukemia/lymphoma on chemotherapy in Uganda: Incidence, risk factors, and immediate outcomes

Abstract

Background: Acute leukemia and lymphoma are the most common childhood malignancies worldwide, accounting for 30% of childhood cancer cases and acute lymphoblastic leukemia (ALL) constitutes 75-80% of paediatric leukemias. Chemotherapy of acute lymphoblastic leukemia/lymphoma (ALL/LBL) involves the use of steroids and L-asparaginase among others, both of which are known to induce hyperglycemia. Hyperglycemia in these patients is associated with increased morbidity and mortality. In Uganda, the burden of hyperglycaemia among children with ALL/LBL on chemotherapy is unknown. We postulated that majority of hyperglycemia incidents in these patients remain undiagnosed and is associated with poor outcomes. Objective: To determine the incidence, risk factors, and immediate outcomes of hyperglycemia among children with acute lymphoblastic leukemia/lymphoma on chemotherapy in Uganda. Methodology: This was a hospital-based prospective cohort study carried out at the 2 main paediatric cancer treatment sites in Uganda (Mulago National Referral Hospital and Uganda Cancer institute) from March to August 2022. A total of 84 participants with ALL and LBL on either induction or re-induction chemotherapy were recruited and each followed up for one month. A random blood glucose (RBG) level was determined at pre-induction and on days 8, 15, 22, and 29. Hyperglycemia was defined as a random blood glucose concentration of ≥200 mg/dl (11.1mmol/l) in two or more determinations. RBG rather than Fasting Blood Glucose was preferred as many of these unwell children travel from home for each round of chemotherapy and would not easily tolerate long periods of fasting. The data was analyzed using STATA 16 and reported as frequencies, means and proportions. Logistic and Cox regression analysis was used to determine factors associated with hyperglycemia. Results: The mean age (SD) was 9.2(±4.2) years. Majority were males 55/84 (65.5%) and younger than 10 years of age (56.0%). Of these, 8/84 children developed hyperglycemia (9.5%)(95% CI (3.2-18.1)). The patients who developed hyperglycemia were all in the age range of 8-16 years, 6/8 (75%) of them were females, 4/8 were overweight/obese and most, 7/8 (87.5%) developed hyperglycemia during induction phase commonly in the second and third weeks. 5/8 (62.5%) developed DKA and they all received insulin therapy. Only female gender was independently associated with hyperglycemia, P=0.026. xii Also, 6/8 children with hyperglycemia developed at least one febrile illness and only one of them died. In 7/8, the hyperglycemia resolved in the third and fourth weeks except for one patient whose hyperglycemia persisted until the sixth week. Conclusion: The cumulative incidence of hyperglycemia in children with ALL and LBL on induction chemotherapy using current guidelines is high at 95 per 1000. Most occur in the second and third weeks of induction and present with DKA but with no increased mortality. Female children are most at risk. Recommendation: Children with ALL/LBL in Uganda on induction chemotherapy using current treatment guidelines should be screened for hyperglycemia especially in the second and third weeks of induction as they may require treatment for DKA. Keywords: Hyperglycemia, Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma.