Preemptive NUDT15 Genotyping and Its Impact on Febrile Neutropenia in Pediatric Patients With Acute Lymphoblastic Leukemia in Taiwan

Abstract

This study investigated whether preemptive NUDT15 genotyping can reduce episodes of febrile neutropenia during the continuation phase of acute lymphoblastic leukemia (ALL) treatment. This retrospective cohort study enrolled 243 children with ALL who were treated according to the Taiwan Pediatric Oncology Group protocol at the National Taiwan University Hospital. The patients were divided into those who underwent preemptive NUDT15 genotyping (n=30) and historical controls (n=213). Febrile neutropenia episodes were compared between groups stratified by risk classification (standard risk [SR], high-risk [HR], very high-risk [VHR] groups). Multivariate analysis was performed, and the dosage was adjusted for age, sex, and mercaptopurine. Preemptive genotyping did not significantly reduce febrile neutropenia episodes in the SR, HR, and VHR patient groups-although a general trend toward reduction was observed. VHR patients with compound heterozygous NUDT15 polymorphisms had a significantly higher risk (risk ratio: 5.6, P =0.001). Younger age at diagnosis was determined to be a predictor of febrile neutropenia. Preemptive NUDT15 genotyping did not significantly reduce febrile neutropenia episodes in our cohort of pediatric patients with ALL, although it allowed a potential reduction in HR patients. Clinicians should consider preemptive testing, particularly in HR and VHR patient groups, to optimize ALL treatments and reduce adverse events.

Keywords: NUDT15; acute lymphoblastic leukemia; febrile neutropenia; mercaptopurine; pediatric oncology.