Central nervous system (CNS) status in pediatric acute lymphoblastic leukemia (ALL) is a key prognostic factor that makes precise detection critical. Flow cytometry (FCM) offers a higher detection rate than conventional cytology (CC); however, results are considered negative with 10 FCM events, limiting its sensitivity. This study analyzed the cerebrospinal fluid from 173 pediatric patients with ALL using both CC and FCM, characterizing immunoglobulin heavy chain rearrangement clonotypes using next-generation sequencing (NGS). The sensitivities of CC and FCM were similar (P = 0.824) when the standard FCM positivity threshold was used. Receiver operating characteristic analysis based on NGS showed ≥ 3 events as the optimal FCM positivity cutoff, significantly improving sensitivity over CC (P = 0.005). Among patients treated according to the Taiwan Pediatric Oncology Group 2013 ALL protocol, FCM positivity correlated with lower event-free survival (EFS) and higher cumulative incidence of CNS relapse (CIRCNS). Patients with hyperdiploidy who were CC-negative/FCM-positive had worse EFS and CIRCNS when receiving less intensive CNS-directed treatments. The three-event cutoff for FCM positivity enhances the detection of CNS involvement in pediatric ALL and, when combined with CC, identifies patients at a higher risk of CNS relapse, highlighting the potential need for treatment intensification.
Chou et al. (Fri,) studied this question.