title: Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients.
abstract: Neuroblastoma is an aggressive pediatric tumor accounting for ~15% of cancer-associated mortalities in children. Despite the current intensive therapy, >50% of high-risk patients experience tumor relapse or regrowth caused by the activation of minimal residual disease (MRD). Although several MRD detection protocols using various reverse transcription-quantitative polymerase chain reaction (RT-qPCR) markers have been reported to evaluate the therapeutic response and disease status of neuroblastoma patients, their clinical significance remains elusive. The present study reports two high-risk neuroblastoma patients, whose MRD was consecutively monitored using 11 RT-qPCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) during their course of treatment. The two patients initially responded to the induction therapy and reached MRD-negative status. The patients' MRD subsequently became positive with no elevation of their urinary homovanillic acid, urinary vanillylmandelic acid and serum neuron-specific enolase levels at 13 or 19 weeks prior to the clinical diagnosis of tumor relapse or regrowth. The present cases highlight the possibility of consecutive MRD monitoring using 11 markers to enable an early detection of tumor relapse or regrowth in high-risk neuroblastoma patients.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirase
authors.affiliation: Department of Hematology and Oncology, Kobe Children's Hospital, Kobe 654-0081, Japan.
authors.forename: Atsuro
authors.initials: A
authors.lastname: Saitoh
authors.affiliation: Department of Epidemiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Tri Budi
authors.initials: TB
authors.lastname: Hartomo
authors.affiliation: Department of Hematology and Oncology, Kobe Children's Hospital, Kobe 654-0081, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Kozaki
authors.affiliation: Department of Hematology and Oncology, Kobe Children's Hospital, Kobe 654-0081, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yanai
authors.affiliation: Department of Hematology and Oncology, Kobe Children's Hospital, Kobe 654-0081, Japan.
authors.forename: Daiichiro
authors.initials: D
authors.lastname: Hasegawa
authors.affiliation: Department of Hematology and Oncology, Kobe Children's Hospital, Kobe 654-0081, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Kawasaki
authors.affiliation: Department of Hematology and Oncology, Kobe Children's Hospital, Kobe 654-0081, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kosaka
authors.affiliation: Department of Medical Rehabilitation, Kobe Gakuin University, Kobe 651-2180, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hayakawa
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Department of Epidemiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Hisahide
authors.initials: H
authors.lastname: Nishio
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Department of Epidemiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nishimura
keywords: minimal residual disease; neuroblastoma; regrowth; relapse