International Journal of Hematology

DOI: 10.1007/s12185-019-02720-z Pages: 566-574

Significance of FLT3-tyrosine kinase domain mutation as a prognostic factor for acute myeloid leukemia

1. Nippon Medical School, Department of Hematology

2. Komagome Hospital, Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center

3. NTT Medical Center Tokyo, Department of Hematology

4. Nagano Red Cross Hospital, Department of Hematology

5. Jichi Medical University, Division of Hematology, Department of Medicine

6. St. Luke’s International Hospital, Hemato-Oncology Department

7. Kyoto Daini Hospital, Department of Hematology, Japanese Red Cross

8. Jichi Medical University Saitama Medical Center, Division of Hematology

9. Yokohama Minami Kyousai Hospital, Department of Hematology

10. Chiba Aoba Municipal Hospital, Department of Hematology

11. Chiba University Hospital, Department of Hematology

12. Eiju General Hopital, Department of Hematology

13. Kyoto University, Department of Hematology and Oncology, Graduate School of Medicine

14. Japanese Red Cross Kyoto Daiichi Hospital, Department of Hematology

15. Kyoto Prefectural University of Medicine, Division of Hematology and Oncology

16. Toranomon Hospital, Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations

17. Saga University, Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine

18. National Cancer Center Hospital, Department of Hematopoietic Stem Cell Transplantation

Correspondence to:
Hiroki Yamaguchi
Tel: +81-3-3822-2131



The prognostic significance of FLT3-tyrosine kinase domain (TKD) mutations remains unknown. To investigate the prognostic impact of FLT3-TKD, 676 de novo acute myeloid leukemia (AML), we retrospectively analyzed cases and conducted a review of the literature. Of the 676 de novo AML cases, 34 (5.0%) were FLT3-TKD-positive; both FLT3-TKD and FLT3-ITD were noted in only two cases (0.3%). Although no significant differences in relapse-free survival (RFS) were noted, FLT3-TKD-positive cases showed better prognoses than FLT3-ITD-positive cases (FLT3-TKD versus FLT3-ITD, p = 0.152). For overall survival (OS), although FLT3-TKD-positive cases showed prognoses similar to those for FLT3-WT cases, their prognoses were significantly better than those of FLT3-ITD-positive cases (FLT3-TKD versus FLT3-ITD, p = 0.032). Moreover, the 5-year OS for FLT3-TKD-positive cases was 46.1%, indicating that this as an intermediate prognosis group. Although no reports from Asia have indicated a frequency of FLT3-TKD-positive cases > 10%, several reports from Europe and the United States have indicated frequencies > 10%. This suggests the possibility that FLT3-TKD-positive cases are less common in Asia than in Europe and the United States. We anticipate that in the future, the appearance of targeting agents, such as FLT3 inhibitors, will improve the prognosis of FLT3-TKD-positive AML relative to that of FLT3-WT AML.

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