TPMT and ITPA genotypes significantly influence the metabolism of 6MP. DNA-TG may prove to be a more relevant pharmacokinetic parameter for monitoring 6MP treatment intensity than cytosolic metabolites. Prospective trials are needed to evaluate the usefulness of DNA-TGN for individual dose adjustments in childhood ALL maintenance therapy.

Background Metabolic syndrome (MetS) is frequent among survivors of childhood hematopoietic stem‐cell transplantation (HSCT), but assessment of risk factors is challenged by survivor and participation bias in long‐term follow‐up studies. Methods A cohort of 395 pediatric patients transplanted between 1980 and 2018 was investigated. MetS was assessed at follow‐up between December 2018 and March 2020. Two composite outcomes ((a) combining MetS and death, (b) combining MetS, death, and nonparticipation) were considered to address the risk of selection bias. Results Among 234 survivors invited to the follow‐up, 96 individuals (median age 27 years) participated. MetS prevalence was 30% among participants. The only significant HSCT risk factor was a variable combining HSCT indication and conditioning with total‐body irradiation (TBI) (p = .0011). Compared to acute leukemias (AL) treated with high‐grade TBI (8–12 Gy), a lower MetS prevalence was seen for nonmalignant diseases treated with no/low‐grade TBI (0–4.5 Gy) (OR = 0.04, 95% confidence interval (CI): 0.00–0.23). Analyses of the composite outcomes indicated overestimation of the effect of high‐grade TBI due to selection bias. Scrutiny showed strong residual confounding between HSCT indication and high‐grade TBI within AL‐patients. The HSCT effect on MetS reflected HSCT effects on high‐density‐lipoprotein (HDL) and triglycerides. Compared to AL treated with high‐grade TBI, nonmalignant diagnoses treated with no/low‐grade TBI had higher HDL (+40%, 95% CI: +21% to +62%) and lower triglyceride (−59%, 95% CI: −71% to −42%). Conclusion The TBI effect on MetS may be overestimated in follow‐up studies due to selection bias and confounding. The TBI effect was confined to the potentially modifiable MetS criteria  HDL and triglyceride.

Context Survivors of pediatric hematopoietic stem cell transplantation (HSCT) have increased risk of developing metabolic syndrome (MetS), but the mechanisms are poorly understood. Objective To test the hypothesis that insufficient secretion of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) plays a pathogenetic role in HSCT survivors with MetS. Design Cross-sectional cohort study. Setting The Danish national referral center for HSCT. Patients or Other Participants Forty-two male HSCT survivors (median age of 28.9 years) studied median 21.2 years from HSCT. Fifteen age- and sex-matched healthy controls. Intervention None. Main Outcome Measures Glucose metabolism and incretin hormones (measured in an oral glucose tolerance test (OGTT)) and MetS-criteria. The hypothesis was formulated before data collection. Results GLP-1, GIP, and glucagon during an OGTT were similar in patients and controls, with no overall difference between survivors with (24%) and without MetS. However, fasting glucagon was significantly higher in patients with hypertriglyceridemia (Mean Difference (MD): 6.1 pmol/L, 95%Confidence Interval (CI): 1.5 to 10.8, p = 0.01), and correlated with HDL (MD: 4.7 mmol/L, 95%CI: -0.6 to 9.9, p = 0.08), android-gynoid ratio (correlation coefficient (r) = 0.6, p = 0.0001) and waist-hip ratio (r = 0.5, p = 0.002). A similar pattern was seen for GIP, correlating positively with triglyceride (MD: 60%, 95%CI: 44 to 82, p = 0.002). GIP levels were significantly increased in patients treated with total body irradiation (TBI) (MD: 165%, 95%CI: 118 to 230, p = 0.004), that was found to be a significant risk factor for MetS. Conclusion This study demonstrates an altered production of incretin hormones in HSCT survivors previously treated with TBI, developing dyslipidemia and abdominal adiposity.