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Impact of FLT3-ITD allele ratio and ITD length on therapeutic outcome in cytogenetically normal AML patients without NPM1 mutation

Bone Marrow Transplantation volume 55, pages 740–748 (2020)Cite this article

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Abstract

Mutations of internal tandem duplication in FMS-like tyrosine kinase 3 (FLT3-ITD) contribute to poor prognosis in cytogenetically normal acute myeloid leukemia (CN-AML). Chemotherapy has limited effect, while allogeneic hematopoietic stem cell transplantation (allo-HSCT) plus sorafenib maintenance is a promising protocol to improve their therapeutic outcome. However, the prognostic significance of FLT3-ITD mutant status remains controversial. To investigate this, we detected FLT3-ITD mutant ratio (high and low) and length (long and short) in enrolled 184 CN-AML patients without NPM1 mutation, and evaluated their impact on complete remission (CR), overall survival (OS), relapse-free survival (RFS) and relapse risk (RR) after chemotherapy or allo-HSCT plus sorafenib maintenance. Our studies showed that FLT3-ITD mutation had negative impact on chemotherapeutic response, OS and RFS in CN-AML patients. There was no significant difference in CR rate between high and low ratio, or long and short length. Increasing ITD mutant ratio and length were associated with decreasing OS, and long length had shorter RFS and higher RR than the short after chemotherapy. Allo-HSCT plus sorafenib maintenance was an effective strategy to improve RFS and decrease relapse probability in FLT3-ITD AML patients, and benefited to these regardless of mutant ratio, and those with long length instead of the short.

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Funding

This work was supported by the National Natural Science Foundation of China (81570152); Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (LC2016YM005); and Science and Technology Planning Project of Guangdong (2014A020212185).

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Authors and Affiliations

  1. Department of Hematology, Nanfang Hospital, Southern Medical University, Guangdong, 510515, China

    Fang Chen, Junya Sun, Changxin Yin, Jiaying Cheng, Jinle Ni, Ling Jiang, Qiang Wang, Guopan Yu, Yongqiang Wei, Xiaoli Liu, Jing Sun & Xuejie Jiang

  2. Department of Hematology, Central Hospital of Xiangtan, Xiangtan, 411100, Hunan, China

    Fang Chen

  3. Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Bing Z. Carter

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Contributions

FC: Development of methodology, acquisition of data, analysis and interpretation of data, writing the manuscript and technical support. JS: Development of methodology, acquisition of data, analysis and interpretation of data. CY: Development of methodology, acquisition of data, technical and material support. JN: Acquisition of data, analysis and interpretation of data. JC: Acquisition of data. LJ: Analysis and interpretation of data and editing the manuscript. GY: Analysis and interpretation of data, writing the manuscript. JS: Editing the manuscript and administrative support. YW and BZC: Editing the manuscript, administrative support, and study supervision. XJ: Conception and design, development of methodology, analysis and interpretation of data, writing the manuscript, administrative and technical support, and study supervision. FC, JS, CY, and JC contributed equally to this work.

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Correspondence to Xuejie Jiang.

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This study was conducted in accordance with the Declaration of Helsinki, and the protocols approved by the ethics committee at Nanfang Hospital, Guangzhou China

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Chen, F., Sun, J., Yin, C. et al. Impact of FLT3-ITD allele ratio and ITD length on therapeutic outcome in cytogenetically normal AML patients without NPM1 mutation. Bone Marrow Transplant 55, 740–748 (2020). https://doi.org/10.1038/s41409-019-0721-z

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