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Clinical significance of FLT3-ITD/CEBPA mutations and minimal residual disease in cytogenetically normal acute myeloid leukemia after hematopoietic stem cell transplantation

  • Original Article – Clinical Oncology
  • Published:
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Abstract

Purpose

Genetic changes have prognostic significance in cytogenetically normal acute myeloid leukemia (CN-AML). We set out to evaluate the prognostic of 6 gene mutations in CN-AML.

Methods

We performed a mutational analysis and evaluated prognostic findings of six genes (NPM1, CEBPA, DNMT3A, FLT3-ITD, FLT3-TKD, and C-KIT) in 428 CN-AML patients at our center over 10 years.

Results

A total of 282 patients (65.9%) had at least one gene mutation, and the mutation frequencies were as follows: 29.7% (NPM1), 24.1% (CEBPA), 20.1% (FLT3-ITD), 4.0% (FLT3-TKD), 11.9% (DNMT3A), and 4.7% (C-KIT). Multivariate analysis indicated that FLT3-ITDmut and CEBPAwt were independent risk factors correlated with poor overall survival (OS) and disease-free survival (DFS) of CN-AML. Compared with patients who received chemotherapy as consolidation, hematopoietic stem cell transplantation (HSCT) significantly improved OS of CN-AML patients. For standard/high risk patients, HSCT improved both OS and DFS. Combined analysis showed that patients with CEBPAmut/FLT3-ITDwt had the best prognosis, and patients with CEBPAwt/FLT3-ITDmut had the worst OS, with 3-year OS of only 44%. In 212 patients who received HSCT, FLT3-ITD/CEBPA mutations and minimal residual disease (MRD) were correlated with OS and DFS in univariate analysis.

Conclusions

We found that HSCT significantly improves the prognosis of standard/high risk CN-AML patients with superior OS and DFS. Molecular marker analyses, especially combined analysis of the FLT3-ITD and CEBPA status revealed a correlation with the prognosis of CN-AML. For patients who have received HSCT, MRD before transplantation was a strong prognostic marker predicting patient outcome.

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Data availability

All data generated or analyzed during this study are included in this published article.

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Acknowledgements

We would like to thank the patients and the physicians from the department of hematology, The First Affiliated Hospital of Soochow University.

Funding

This study was supported by grants from the National Natural Science Foundation of China (Grant No. 81100342, 81270591, 81670132), Jiangsu Province of China (BE2016665, BRA2011218), Jiangsu Provincial Special Program of Medical Science (BL2012005), and Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Author notes

  1. Hong Wang, Xue-Qian Li and Tian-Tian Chu contributed equally to this work.

Authors and Affiliations

  1. Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, 215000, China

    Hong Wang, Xue-Qian Li, Tian-Tian Chu, Shi-Yu Han, Jia-Qian Qi, Ya-Qiong Tang, Hui-Ying Qiu, Cheng-Cheng Fu, Xiao-Wen Tang, Chang-Geng Ruan, De-Pei Wu & Yue Han

  2. Collaborative Innovation Center of Hematology, Institute of Blood and Marrow Transplantation, Suzhou, China

    Hong Wang, Xue-Qian Li, Tian-Tian Chu, Shi-Yu Han, Jia-Qian Qi, Ya-Qiong Tang, Hui-Ying Qiu, Cheng-Cheng Fu, Xiao-Wen Tang, Chang-Geng Ruan, De-Pei Wu & Yue Han

  3. Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, China

    Hong Wang, Jia-Qian Qi, Ya-Qiong Tang, Hui-Ying Qiu, Cheng-Cheng Fu, Xiao-Wen Tang, Chang-Geng Ruan, De-Pei Wu & Yue Han

  4. State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China

    Hui-Ying Qiu, Cheng-Cheng Fu, Xiao-Wen Tang, Chang-Geng Ruan, De-Pei Wu & Yue Han

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  1. Hong Wang
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Contributions

HW collected data, made analysis and wrote the manuscript and provide funding support. X-QL and T-TC participated in data collection and analysis. S-YH, J-QQ and Y-QT participated in data collection. H-YQ, C-CF, X-WT and C-GR supervised the study and revised the manuscript. YH and D-PW conceived of and designed the study and provided funding support. All authors have reviewed the manuscript. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to De-Pei Wu or Yue Han.

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Conflict of interest

The authors declare no conflicts of interest.

Ethics approval

This retrospective chart review study involving human participants was performed in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the Committee for the Ethical Review of Research at First Affiliated Hospital of Soochow University.

Consent for participate

Informed consent was obtained from all patients prior to data collection and the study was approved by the Committee for the Ethical Review of Research at First Affiliated Hospital of Soochow University.

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The participants have consented to the submission of the study to the journal.

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Wang, H., Li, XQ., Chu, TT. et al. Clinical significance of FLT3-ITD/CEBPA mutations and minimal residual disease in cytogenetically normal acute myeloid leukemia after hematopoietic stem cell transplantation. J Cancer Res Clin Oncol 147, 2659–2670 (2021). https://doi.org/10.1007/s00432-021-03530-9

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