Minimal residual disease detected by droplet digital PCR in peripheral blood stem cell grafts has a prognostic impact on high-risk neuroblastoma patients

Nanako Nino; Toshiaki Ishida; Naoko Nakatani; Kyaw San Lin; Kaung Htet Nay Win; Cho Yee Mon; Akihiro Nishimura; Shotaro Inoue; Akihiro Tamura; Nobuyuki Yamamoto; Suguru Uemura; Atsuro Saito; Takeshi Mori; Daiichiro Hasegawa; Yoshiyuki Kosaka; Kandai Nozu; Noriyuki Nishimura

doi:10.1016/j.heliyon.2022.e10978

Minimal residual disease detected by droplet digital PCR in peripheral blood stem cell grafts has a prognostic impact on high-risk neuroblastoma patients

Heliyon. 2022 Oct 8;8(10):e10978. doi: 10.1016/j.heliyon.2022.e10978. eCollection 2022 Oct.

Authors

Nanako Nino¹, Toshiaki Ishida², Naoko Nakatani¹, Kyaw San Lin¹, Kaung Htet Nay Win³, Cho Yee Mon³, Akihiro Nishimura¹, Shotaro Inoue¹, Akihiro Tamura¹, Nobuyuki Yamamoto¹, Suguru Uemura², Atsuro Saito², Takeshi Mori², Daiichiro Hasegawa², Yoshiyuki Kosaka², Kandai Nozu¹, Noriyuki Nishimura³

Affiliations

¹ Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
² Department of Hematology and Oncology, Kobe Children's Hospital, Kobe, Japan.
³ Department of Public Health, Kobe University Graduate School of Health Science, Kobe, Japan.

Abstract

More than half of high-risk neuroblastoma (NB) patients have experienced relapse due to the activation of chemoresistant minimal residual disease (MRD) even though they are treated by high-dose chemotherapy with autologous peripheral blood stem cell (PBSC) transplantation. Although MRD in high-risk NB patients can be evaluated by quantitative PCR with several sets of neuroblastoma-associated mRNAs (NB-mRNAs), the prognostic significance of MRD in PBSC grafts (PBSC-MRD) is unclear. In the present study, we collected 20 PBSC grafts from 20 high-risk NB patients and evaluated PBSC-MRD detected by droplet digital PCR (ddPCR) with 7NB-mRNAs (CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNA). PBSC-MRD in 11 relapsed patients was significantly higher than that in 9 non-relapsed patients. Patients with a higher PBSC-MRD had a lower 3-year event-free survival (P = 0.0148). The present study suggests that PBSC-MRD detected by ddPCR with 7NB-mRNAs has a prognostic impact on high-risk NB patients.

Keywords: Droplet digital PCR (ddPCR); Minimal residual disease (MRD); Neuroblastoma (NB); Neuroblastoma-associated mRNAs (NB-mRNAs); Peripheral blood stem cell (PBSC).