AKUT LENFOBLASTİK LÖSEMİ HASTALARINDA İLAÇ İLİŞKİLİ DİYABET SIKLIĞI VE RİSK FAKTÖRLERİ

Abstract

Hyperglycemia is a common complication during the treatment of Acute Lymphoblastic Leukemia (ALL). Its frequency varies between 8.4% and 35% as in previous studies. The main factor responsible for hyperglycemia is high-dose glucocorticoids and asparaginases in the treatment protocols. It is known that glucocorticoids increase gluconeogenesis and reduce the uptake of glucose into the cell, thus causing insulin resistance, and also affect pancreatic β cells hereby reducing insulin secretion. Asparaginases also lead to hyperglycemia, mainly by reducing insulin production. Factors such as advanced age, female sex, obesity, family history of diabetes, and high-risk disease are among the risk factors for drug-induced hyperglycemia in ALL patients. The objective of our study is to compare different treatment protocols administered in pediatric ALL patients in terms of hyperglycemia risk, to examine the protocols administered in the treatment of hyperglycemia, to determine the risk factors for hyperglycemia and to identify the patient group that should be monitored for blood glucose levels more closely. At our hospital, St Jude Total XV treatment protocol was administered between 2008 and 2016, and ALL IC BFM 2009 treatment protocol was administered between 2016 and 2023. The cumulative doses of glucocorticoids and asparaginase given in these two protocols were different. In our study, patients aged 1-18 years who received ALL treatment between February 2008 and September 2023 at Ihsan Dogramacı Children’s Hospital of Faculty of Medicine at Hacettepe University were retrospectively analyzed. We analyzed demographic and oxological data of the patients, family history of diabetes, characteristics related to the ALL risk group, treatment protocols and cumulative glucocorticoid and asparaginase doses, severity and duration of hyperglycemia, the phase of the treatment protocol in which hyperglycemia developed, glucose, insulin, C peptide and HbA1C levels during hyperglycemia. The median age of the 278 patients included in the study was 5 years. 115 (41.4%) were female and 163 (58.6%) were male. 173 patients (62.2%) received the St Jude Total XV treatment protocol, while 105 patients (37.8%) received the ALL IC BFM 2009 treatment protocol. 60/278 (21.5%) developed short-term hyperglycemia and 45/278 (16.2%) developed diabetes. The phases of chemotherapy protocols that short-term hyperglycemia and diabetes developed most frequently were remission induction (%15.4, %9.7, respectively) and relapse (%7.4, %26 respectively) periods. There was no difference between the two protocols in terms of the frequency of short-term hyperglycemia and diabetes (p=0.617 and p=0.180, respectively). When the risk factors for diabetes were examined during the remission induction period, which is one of the most common period diabetes is observed, it was seen that advanced age, female gender and central nervous system (CNS) involvement were independent risk factors. It was observed that the risk of developing diabetes increases by 1.39 times with each year of age, 2.87 times with the female sex, 4.16 times with CNS involvement, and 3.85 times with traumatic LP. In univariate analyses, white blood cells ≥50.000 x10 3 /µL and T-cell ALL were identified as risk factors for diabetes, whereas they lost significance in multivariate analysis. 25 (55.5%) of the 45 patients with diabetes received insulin therapy. The median duration of insulin use was 24.7 days. In order to investigate the factors affecting the duration of insulin requirement, patients who used insulin for ≤ 4 days were compared with those who used insulin longer. HbA1c levels and the glucose/insulin ratio was higher in the patients who used insulin for more than four days, which means less insulin was secreted in response to the increase in glucose (p=0.002 and p=0.009, respectively). As a result, patient-specific risk factors play more important role in diabetes rather than the differences between treatment protocols in ALL patients. It should be kept in mind that, patients over 10 years of age, female gender, patients with CNS involvement and relapse disease are at higher risk, and blood glucose monitoring should be monitored closely in these patients. Unlike the other studies that are limited to the remission induction period in the treatment of ALL, our study provides information in terms of the frequency of hyperglycemia in all periods of the treatment and contributes to the literature by identifying strong risk factors as a result of investigating many possible risk factors for diabetes.