title: Clinical utility of next-generation sequencing-based minimal residual disease in paediatric B-cell acute lymphoblastic leukaemia.
abstract: We assessed the clinical utility of next-generation sequencing (NGS)-based monitoring of minimal residual disease (MRD) in a uniformly treated cohort of 79 patients with paediatric B-cell acute lymphoblastic leukaemia. Bone marrow samples were collected at the time of diagnosis, days 33 and 80, pre- (4-5 months) and post- (24 months) maintenance therapy time points, and at relapse. We identified leukaemia-specific CDR3 sequences in 72 of 79 patients (91%) and detected MRD in 59 of 232 samples. Although MRD was detected in 28 of 55 samples (51%) on day 33, the frequencies of MRD detection decreased to 25% (16/65) at day 80, 19% (11/58) at 4-5 months and 7·4% (4/54) at 24 months. In a univariate analysis, positive MRD results on day 80 [relative risk (RR) 95% confidence interval (CI) = 7·438 (2·561-21·6), P < 0·001], at 4-5 months [RR (95% CI) = 10·24 (3·374-31·06), P < 0·001], and at 24 months [RR (95% CI) = 19·26 (4·974-74·59), P < 0·001] exhibited statistically significant associations with inferior leukaemia-free survival; this was confirmed using a Cox proportional hazard model. Our study suggests the promising potential of NGS-MRD for patients with B-cell ALL.
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sekiya
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Muramatsu
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuno
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Narita
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kyogo
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Xinan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kawashima
authors.affiliation: Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Sakaguchi
authors.affiliation: Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Asahito
authors.initials: A
authors.lastname: Hama
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
mesh_terms: D000293:Adolescent; D001402:B-Lymphocytes / Q000473:pathology; D001856:Bone Marrow Examination; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual / Q000175:diagnosis*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis*; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D013997:Time Factors
chemical_list: D004273:DNA, Neoplasm
keywords: minimal residual disease; next-generation sequencing; paediatric acute lymphoblastic leukaemia; prognosis for relapse