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Allogeneic transplant can abrogate the risk of relapse in the patients of first remission acute myeloid leukemia with detectable measurable residual disease by next-generation sequencing

Abstract

In patients with acute myeloid leukemia (AML) consolidation treatment options are between allogeneic hematopoietic stem cell transplantation (HCT) and chemotherapy, based on disease risk at the time of initial presentation and age. Measurable residual disease (MRD) following induction chemotherapy could be incorporated as a useful parameter for treatment decisions. The present study evaluated treatment outcomes according to the next-generation sequencing (NGS)-based MRD status and the type of consolidation therapy in patients with normal karyotype (NK)-AML. By sequencing 278 paired samples collected at diagnosis and first remission (CR1), we identified 361 mutations in 124 patients at diagnosis and tracked these at CR1. After excluding mutations associated with age-related clonal hematopoiesis, 82 mutations in 50 of the 124 patients (40.3%) were detected at CR1. Survival benefit was observed in favor of allogeneic HCT over chemotherapy consolidation in the MRDpos subgroup with respect to overall survival (HR 0.294, p = 0.003), relapse-free survival (HR 0.376, p = 0.015) and cumulative incidence of relapse (HR 0.279, p = 0.004) in multivariate analysis, but not in the MRDneg subgroup. In summary, these data support allogeneic HCT in NK-AML patients with detectable MRD by NGS in CR1. Randomized clinical trials will be required to confirm this observation.

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Fig. 1: Frequency of mutations and flow chart of patients with normal karyotype acute myeloid leukemia (NK-AML).
Fig. 2: Survival, relapse risks, and non-relapse mortalities according to the measurable residual disease (MRD) status and the type of consolidation therapy in patients with normal karyotype acute myeloid leukemia (NK-AML).
Fig. 3: Survival, relapse risks, and non-relapse mortalities according to the measurable residual disease (MRD) status at first complete remission.

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Acknowledgements

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT, and Future Planning (NRF-2015R1A2A1A10054579 and NRF-2017R1C1B5017389) and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1720160). This study was supported by a grant (HCRI20018) Chonnam National University Hwasun Hospital Institute for Biomedical Science. This work was also supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2018R1A2A1A05078480) and by the Princess Margaret Cancer Foundation, Toronto, ON, Canada. TK was supported by a scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC, PGS-D). The biospecimens used in this study were provided by the Biobank of Chonnam National University Hwasun Hospital, a member of the Korea Biobank. The whole-exome data used in this study have been deposited in the Clinical & Omics Data Archive (CODA, http://coda.nih.go.kr) under accession # R000007.

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Correspondence to Zhaolei Zhang or Hyeoung-Joon Kim or Dennis Dong Hwan Kim.

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Ahn, JS., Kim, T., Jung, SH. et al. Allogeneic transplant can abrogate the risk of relapse in the patients of first remission acute myeloid leukemia with detectable measurable residual disease by next-generation sequencing. Bone Marrow Transplant (2020). https://doi.org/10.1038/s41409-020-01165-x

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