Huirong Mai1, Qin Li1,2, Guobing Wang3, Ying Wang1, Shilin Liu1, Xue Tang1, Fen Chen1, Guichi Zhou1, Yi Liu1, Tonghui Li1, Lulu Wang1, Chunyan Wang1, Feiqiu Wen1, Sixi Liu4. 1. Department of Hematology and Oncology, Shenzhen Children's Hospital, No. 7019, Yitian Road, Futian District, Shenzhen, China. 2. Department of Hematology and Oncology, Shenzhen Children's Hospital, China Medical University, Shenzhen, China. 3. Pediatrics Research Institute, Shenzhen Children's Hospital, Shenzhen, China. 4. Department of Hematology and Oncology, Shenzhen Children's Hospital, No. 7019, Yitian Road, Futian District, Shenzhen, China. tiger647@126.com.
Abstract
BACKGROUND: Next-generation sequencing (NGS) is an emerging technology that can comprehensively assess the diversity of the immune system. We explored the feasibility of NGS in detecting minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL) based on immunoglobulin and T cell receptor. METHODS: Bone marrow samples were collected pre- and post-treatment with pediatric ALL admitted to Shenzhen Children's Hospital from February 1st, 2020 to January 31st, 2021. We analyzed the MRD detected by NGS, multiparametric flow cytometry (MFC) and real-time quantitative PCR (RQ-PCR), and analyzed risk factors of positive NGS-MRD at the end of B-ALL induction chemotherapy. RESULTS: A total of paired 236 bone marrow samples were collected from 64 children with ALL (58 B-ALL and 6 T-ALL). The decrease in the clonal rearrangement frequency of IGH, IGK, and IGL was generally consistent after treatment. Positive MRD was detected in 57.5% (77/134) of B-ALL and 80% (12/15) of T-ALL by NGS after chemotherapy, which was higher than those detected by MFC and RQ-PCR. In B-ALL patients, MRD results detected by NGS were consistent with MFC (r = 0.708, p < 0.001) and RQ-PCR (r = 0.618, p < 0.001). At the end of induction, NGS-MRD of 40.4% B-ALL was > 0.01% and multivariate analysis indicated that ≧2 clonal rearrangement sequences before treatment were an independent factor of negative NGS-MRD. CONCLUSIONS: NGS is more sensitive than MFC and RQ-PCR for MRD measurement. B-ALL children with ≧2 clonal rearrangements detected by NGS before treatment are difficult to switch to negative MRD after chemotherapy.
BACKGROUND: Next-generation sequencing (NGS) is an emerging technology that can comprehensively assess the diversity of the immune system. We explored the feasibility of NGS in detecting minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL) based on immunoglobulin and T cell receptor. METHODS: Bone marrow samples were collected pre- and post-treatment with pediatric ALL admitted to Shenzhen Children's Hospital from February 1st, 2020 to January 31st, 2021. We analyzed the MRD detected by NGS, multiparametric flow cytometry (MFC) and real-time quantitative PCR (RQ-PCR), and analyzed risk factors of positive NGS-MRD at the end of B-ALL induction chemotherapy. RESULTS: A total of paired 236 bone marrow samples were collected from 64 children with ALL (58 B-ALL and 6 T-ALL). The decrease in the clonal rearrangement frequency of IGH, IGK, and IGL was generally consistent after treatment. Positive MRD was detected in 57.5% (77/134) of B-ALL and 80% (12/15) of T-ALL by NGS after chemotherapy, which was higher than those detected by MFC and RQ-PCR. In B-ALL patients, MRD results detected by NGS were consistent with MFC (r = 0.708, p < 0.001) and RQ-PCR (r = 0.618, p < 0.001). At the end of induction, NGS-MRD of 40.4% B-ALL was > 0.01% and multivariate analysis indicated that ≧2 clonal rearrangement sequences before treatment were an independent factor of negative NGS-MRD. CONCLUSIONS: NGS is more sensitive than MFC and RQ-PCR for MRD measurement. B-ALL children with ≧2 clonal rearrangements detected by NGS before treatment are difficult to switch to negative MRD after chemotherapy.
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