Clinical utility of next‐generation sequencing‐based minimal residual disease in paediatric B‐cell acute lymphoblastic leukaemia. (11th November 2016)

• Record Type: Journal Article
• Authors: Sekiya, Yuko; Xu, Yinyan; Muramatsu, Hideki; Okuno, Yusuke; Narita, Atsushi; Suzuki, Kyogo; Wang, Xinan; Kawashima, Nozomu; Sakaguchi, Hirotoshi; Yoshida, Nao; Hama, Asahito; Takahashi, Yoshiyuki; Kato, Koji; Kojima, Seiji
• Is Part Of: British journal of haematology. Volume 176:Number 2(2017)
• Page Start: 248
• Page End: 257
• Publication Date: 2016-11-11
• Subjects: next‐generation sequencing -- minimal residual disease -- paediatric acute lymphoblastic leukaemia -- prognosis for relapse; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.14420
• Languages: English
• ISSNs: 0007-1048

Abstract

Summary: 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.