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Pretransplant FLT3-ITD levels predict outcome after allogeneic hematopoietic cell transplantation for AML patients in the first remission

Bone Marrow Transplantation volume 55, pages 821–823 (2020)Cite this article

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Patients with AML harboring FLT3-ITD mutations have a poorer outcome and are widely considered to be candidates for allogeneic hematopoietic cell transplant (allo-HCT) during their first complete remission (CR1) [1]. However, disease recurrence following HCT remains the main cause of treatment failure among these patients, which merits further investigation for early predicting relapse. Despite the general applicability, measurable residual disease (MRD) detected by multiparameter flow cytometry (MRDMFC) still exhibits inherent limitations when employed as a predictor for posttransplant outcomes [2]. Increasing evidences have proven the value of specific mutation levels as MRD marker for AML patients [2]. As a common leukemia-specific genetic aberration in AML, FLT3-ITD mutations have been identified as a highly sensitive means of predicting postremission outcomes [3, 4]. Nevertheless, few studies focused on the impact of pre-HCT FLT3-ITD mutant levels on the posttransplant outcomes for patients in CR1. Hence, we conducted a retrospective study to investigate the efficacy of using FLT3-ITD allele frequencies as MRD marker (MRDFLT3-ITD) pre-HCT, for predicting transplant outcomes, and enrolled 84 patients who received allo-HCT during their first remission in the First Affiliated Hospital of Soochow University between January 2012 and June 2017. Patients with acute promyelocytic leukemia or who had received FLT3 inhibitors before and/or after transplantation were excluded. All recipients and donors provided written informed consent for the protocol, which was approved by our hospital’s Ethics Committee.

Treatment before transplantation, conditioning regimen, GVHD prophylaxis, and posttransplant management were carried out as described previously [5]. Samples used for FLT3-ITD detection and MFC were acquired from the same preconditioning marrow aspiration with the median time of 18 (range 12–28) days before HCT. Detection of MRDMFC and MRDFLT3-ITD was performed as described previously, with the cutoff value of 0.1% for MRDMFC and 2.5% for MRDFLT3-ITD [6,7,8]. FLT3-ITD mutant allele frequencies >33% at diagnosis were defined as FLT3-ITDhi [9].

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References

  1. Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. New Engl J Med. 2016;374:2209–21.

    Article  CAS  Google Scholar 

  2. Schuurhuis GJ, Heuser M, Freeman S, Béné M, Buccisano F, Cloos J, et al. Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party. Blood. 2018;131:1275–91.

    Article  CAS  Google Scholar 

  3. Schiller J, Praulich I, Krings RC, Kreuzer KA. Patient-specific analysis of FLT3 internal tandem duplications for the prognostication and monitoring of acute myeloid leukemia. Eur J Haematol. 2012;89:53–62.

    Article  CAS  Google Scholar 

  4. Levis MJ, Perl AE, Altman JK, Gocke CD, Bahceci E, Hill J, et al. A next-generation sequencing-based assay for minimal residual disease assessment in AML patients with FLT3-ITD mutations. Blood Adv. 2018;2:825–31.

    Article  CAS  Google Scholar 

  5. Chen J, Yang L, Fan Y, Xu Y, Han Y, Tang X, et al. Comparison of autologous stem cell transplantation versus haploidentical donor stem cell transplantation for favorable- and intermediate-risk acute myeloid leukemia patients in first complete remission. Biol Blood Marrow Transplant. 2018;24:779–88.

    Article  Google Scholar 

  6. Murphy KM, Levis M, Hafez MJ, Geiger T, Cooper LC, Smith BD, et al. Detection of FLT3 internal tandem duplication and D835 mutations by a multiplex polymerase chain reaction and capillary electrophoresis assay. J Mol Diagn. 2003;5:96–102.

    Article  CAS  Google Scholar 

  7. Jongen-Lavrencic M, Grob T, Hanekamp D, Kavelaars FG, Al HA, Zeilemaker A, et al. Molecular minimal residual disease in acute myeloid leukemia. N Engl J Med. 2018;378:1189–99.

    Article  CAS  Google Scholar 

  8. Zhao XS, Yan CH, Liu DH, Xu LP, Liu YR, Liu KY, et al. Combined use of WT1 and flow cytometry monitoring can promote sensitivity of predicting relapse after allogeneic HSCT without affecting specificity. Ann Hematol. 2013;92:1111–9.

    Article  CAS  Google Scholar 

  9. Linch DC, Hills RK, Burnett AK, Khwaja A, Gale RE. Impact of FLT3(ITD) mutant allele level on relapse risk in intermediate-risk acute myeloid leukemia. Blood. 2014;124:273–6.

    Article  CAS  Google Scholar 

  10. Xuan L, Wang Y, Huang F, Jiang E, Deng L, Wu B, et al. Effect of sorafenib on the outcomes of patients with FLT3-ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation. Cancer. 2018;124:1954–63.

    Article  CAS  Google Scholar 

  11. Battipaglia G, Ruggeri A, Massoud R, El CJ, Jestin M, Antar A, et al. Efficacy and feasibility of sorafenib as a maintenance agent after allogeneic hematopoietic stem cell transplantation for Fms-like tyrosine kinase 3-mutated acute myeloid leukemia. Cancer. 2017;123:2867–74.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by Grant nos. 81500146 and 81700173 from the National Natural Science Foundation of China.

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  1. These authors contributed equally: Li Wan, Mingzhu Xu, Jia Chen, and Zuyi Yang

Authors and Affiliations

  1. The First Affiliated Hospital of Soochow University, Suzhou, China

    Li Wan, Mingzhu Xu, Jia Chen, Zuyi Yang, Mimi Xu, Hongjie Shen, Xiaojin Wu, Shengli Xue, Xiao Ma, Yue Han, Xiaowen Tang, Huiying Qiu, Depei Wu & Yuejun Liu

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  1. Li Wan
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Correspondence to Depei Wu or Yuejun Liu.

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Wan, L., Xu, M., Chen, J. et al. Pretransplant FLT3-ITD levels predict outcome after allogeneic hematopoietic cell transplantation for AML patients in the first remission. Bone Marrow Transplant 55, 821–823 (2020). https://doi.org/10.1038/s41409-019-0576-3

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