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Allogeneic hematopoietic cell transplantation can overcome the adverse prognosis indicated by secondary-type mutations in de novo acute myeloid leukemia

Bone Marrow Transplantation volume 57, pages 1810–1819 (2022)Cite this article

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Abstract

Secondary-type mutations (STMs), namely SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, and STAG2, are more frequently detected in secondary acute myeloid leukemia (AML) than in de novo AML. Whether de novo AML with STMs should be differently managed is, however, unclear. In 394 patients diagnosed with de novo AML who had a normal karyotype, the genetic profiling via targeted deep sequencing of 45 genes revealed 59 patients carrying STMs (STM+). The STM+ group showed shorter overall survival (OS) than the STM− group (5-year OS, 15.3 vs. 31.0%) (hazard ratio [HR]: 1.975, 95% confidence interval [CI]: 1.446–2.699, p < 0.001). Among the 40 STM+ patients who achieved CR, those who received allogeneic HCT (n = 15) showed better OS (5-year OS, 40.0 vs. 12.0%) (HR: 0.423, 95% CI: 0.184–0.975, p = 0.043) and relapse-free survival (5-year, 40.0 vs. 8.0%) (HR: 0.438, 95% CI: 0.189–1.015, p = 0.054) than those who received consolidation chemotherapy only. The cumulative incidence of relapse was lower in the patients who received allogeneic HCT (5-year, 33.3 vs. 60.0%) (HR: 0.288, 95% CI: 0.111–0.746, p = 0.011), and non-relapse mortality was similar between the two groups (p = 0.935). In conclusion, STM is an independent prognostic factor for adverse outcomes in AML that can be overcome by allogeneic HCT.

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Fig. 1: Flow chart of the patients and genetic mutation analysis result.
Fig. 2: Prognostic significance of secondary-type mutation (STM).
Fig. 3: Clinical outcome of the patients with secondary-type mutation (STM) according to allogeneic HCT.

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Data availability

The dataset is available from the corresponding author upon reasonable request.

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Funding

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 the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1720160). This study was supported by a grant (HCRI21006) 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 Korean government (MSIT) (No. 2018R1A2A1A05078480). 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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Author notes

  1. These authors contributed equally: Ga-Young Song, TaeHyung Kim.

Authors and Affiliations

  1. Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea

    Ga-Young Song, Seo-Yeon Ahn, Sung-Hoon Jung, Mihee Kim, Deok-Hwan Yang, Je-Jung Lee, Jae-Sook Ahn & Hyeoung-Joon Kim

  2. Department of Computer Science, University of Toronto, Toronto, ON, Canada

    TaeHyung Kim & Zhaolei Zhang

  3. The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada

    TaeHyung Kim & Zhaolei Zhang

  4. Genomic Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea

    Seung Hyun Choi, Mi Yeon Kim, Jae-Sook Ahn & Hyeoung-Joon Kim

  5. Division of Hematology-Oncology, Samsung Medical Center, Seoul, South Korea

    Chul Won Jung & Jun-Ho Jang

  6. Department of Hematology, The Catholic University of Korea, Seoul, South Korea

    Hee Je Kim

  7. Department of Hematology-Oncology, Kyungpook National University Hospital, Daegu, South Korea

    Joon Ho Moon & Sang Kyun Sohn

  8. Department of Hematology-Oncology, Soon Chun Hyang University Hospital, Seoul, South Korea

    Jong-Ho Won & Seong-Kyu Park

  9. Department of Hematology-Oncology, Dong-A University College of Medicine, Busan, Korea

    Sung-Hyun Kim

  10. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

    Zhaolei Zhang

  11. Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada

    Dennis Dong Hwan Kim

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Contributions

H-JK, J-SA, and DDHK designed the study and all authors prepared the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Jae-Sook Ahn, Hyeoung-Joon Kim or Dennis Dong Hwan Kim.

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This retrospective study was approved by the institutional ethics committee of each participating institution and conducted in accordance with the Declaration of Helsinki. The committee waived the need for informed patient consent because of the retrospective nature of the work.

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Song, GY., Kim, T., Ahn, SY. et al. Allogeneic hematopoietic cell transplantation can overcome the adverse prognosis indicated by secondary-type mutations in de novo acute myeloid leukemia. Bone Marrow Transplant 57, 1810–1819 (2022). https://doi.org/10.1038/s41409-022-01817-0

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