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Maintenance sorafenib is superior to prophylactic donor lymphocyte infusion at improving the prognosis of acute myeloid leukemia with FMS-like tyrosine kinase 3 internal tandem duplication after allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 56, pages 293–296 (2021)Cite this article

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Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) occurs in ~25% of adult acute myeloid leukemia (AML) cases and is an independent risk factor for increased risk of relapse and inferior survival, even after allogeneic hematopoietic cell transplantation (allo-HSCT) [1]. Prophylactic donor lymphocyte infusion (pDLI) after allo-HSCT is a classical treatment for preventing relapse in some high-risk AML patients. In recent years, sorafenib was proven effective at improving the prognosis of FLT3-ITD-positive AML patients in the setting of post transplantation maintenance therapy [2]. However, there are limited data comparing maintenance sorafenib with pDLI at preventing relapse in FLT3-ITD-positive AML patients after allo-HSCT.

We performed a retrospective study with 68 FLT3-ITD-positive AML patients who received allo-HSCT in our center from January 2014 to December 2018. Their donors were HLA-identical related donors (n = 21), unrelated donors (n = 7), and HLA haplo-identical related donors (n = 40). To prevent AML relapse after allo-HSCT, 24 patients received maintenance sorafenib (group A), 12 patients received pDLI (group B), and the remaining 32 patients who did not receive pDLI or maintenance sorafenib post transplantation were included as the control group (group C). All patients who received pDLI or maintenance sorafenib had full donor chimerism and were negative for minimal residual disease (MRD) and the FLT3-ITD mutation. MRD monitoring after chemotherapy or allo-HSCT was performed using standard polymerase chain reaction (PCR)-based molecular techniques for FLT3. The maintenance concentration of cyclosporin A (CsA) was 150–250 ng/ml from day −3 to day +90 after transplantation and then tapered at 33% per month for discontinuation on day +150 to +180 unless GVHD developed. When patients received a pDLI, immunosuppressive agents were continued, and additional immunosuppressive agents were not administered to patients unless DLI-related GVHD developed.

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Fig. 1: The outcomes of FLT3-ITD-positive AML patients after allo-HSCT.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant no. 81870153) and the Science and Technology Department of Zhejiang Province (grant no. 2015C03038).

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  1. These authors contributed equally: Jimin Shi, Liqin Cao

Authors and Affiliations

  1. Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Jimin Shi, Liqin Cao, Yi Luo, Yanmin Zhao, Yamin Tan, Jian Yu, Xiaoyu Lai, Yuanyuan Zhu, Yongxian Hu, Jingsong He, Jie Sun, Weiyan Zheng, Guoqing Wei & He Huang

  2. Institute of Hematology, Zhejiang University, Hangzhou, China

    Jimin Shi, Liqin Cao, Yi Luo, Yanmin Zhao, Yamin Tan, Jian Yu, Xiaoyu Lai, Yuanyuan Zhu, Yongxian Hu, Jingsong He, Jie Sun, Weiyan Zheng, Guoqing Wei & He Huang

  3. Zhejiang Province Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, China

    Jimin Shi, Liqin Cao, Yi Luo, Yanmin Zhao, Yamin Tan, Jian Yu, Xiaoyu Lai, Yuanyuan Zhu, Yongxian Hu, Jingsong He, Jie Sun, Weiyan Zheng, Guoqing Wei & He Huang

  4. Stem Cell Institute, Zhejiang University, Hangzhou, China

    Jimin Shi, Liqin Cao, Yi Luo, Yanmin Zhao, Yamin Tan, Jian Yu, Xiaoyu Lai, Yuanyuan Zhu, Yongxian Hu, Jingsong He, Jie Sun, Weiyan Zheng, Guoqing Wei & He Huang

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Correspondence to He Huang.

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Shi, J., Cao, L., Luo, Y. et al. Maintenance sorafenib is superior to prophylactic donor lymphocyte infusion at improving the prognosis of acute myeloid leukemia with FMS-like tyrosine kinase 3 internal tandem duplication after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 56, 293–296 (2021). https://doi.org/10.1038/s41409-020-01015-w

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