International Journal of Hematology

DOI: 10.1007/s12185-017-2395-x Pages: 586-595

Risk-stratified therapy for children with FLT3-ITD-positive acute myeloid leukemia: results from the JPLSG AML-05 study

1. Okayama University Hospital, Department of Pediatric Hematology/Oncology

2. Nagoya Medical Center, National Hospital Organization, Clinical Research Center

3. Osaka Medical Center, Department of Pediatrics, National Hospital Organization

4. Children’s Cancer Center, National Center for Child Health and Development, Division of Leukemia and Lymphoma

5. Yokohama City University, Department of Pediatrics

6. Aichi Gakuin University, Department of Nutritional Science

7. Shiga Medical University, Department of Pediatrics

8. Mie University, Department of Pediatrics

9. Hirosaki University, Department of Pediatrics

10. Miyazaki University, Department of Pediatrics

11. St. Marianna University, Department of Pediatrics, School of Medicine

12. Toho University Omori Medical Center, Department of Pediatrics

13. Kyushu Cancer Center, Department of Pediatrics

14. Saitama Children’s Medical Center, Department of Hematology/Oncology

15. Kanagawa Children’s Medical Center, Department of Hematology/Oncology

16. Kobe Children’s Medical Center, Department of Hematology/Oncology

17. National Center for Child Health and Development, Department of Pediatric Hematology and Oncology Research

18. Gunma Children’s Medical Center, Department of Hematology/Oncology

19. Kyoto University, Department of Clinical Biostatistics, Graduate School of Medicine

20. Kyoto University, Department of Human Health Science

21. Gunma University, Department of Pediatrics

Correspondence to:
Akira Shimada
Tel: +81-86-235-7249



Acute myeloid leukemia harboring internal tandem duplication of FMS-like tyrosine kinase 3 (AMLFLT3-ITD) is associated with poor prognosis. We evaluated the results of the AML-05 study, in which all AMLFLT3-ITD patients were assigned to receive hematopoietic stem cell transplantation (HSCT) in the first remission (1CR). We also investigated the effects of additional genetic alterations on FLT3-ITD. The 5-year overall survival (OS) and event-free survival (EFS) rates among the 47 AMLFLT3-ITD patients were 42.2 and 36.8%, respectively. The 5-year disease-free survival rate among 29 patients without induction failure was 58.4%. We defined the allelic ratio (AR) of FLT3-ITD to WT > 0.7 as high. Significant differences were found in OS (AR-high, 20% vs. AR-low, 66%, p < 0.001) and EFS (13 vs. 50%, p = 0.004). All five patients with concurrent NPM1 mutations survived, while seven of eight patients who expressed the NUP98-NSD1 chimera failed to achieve 1CR and died. Multivariate analysis revealed that AR > 0.7 and expression of the NUP98-NSD1 chimera strongly impacted OS and EFS. Although all the AMLFLT3-ITD patients received HSCT at 1CR, the treatment outcome of AMLFLT3-ITD patients did not improve compared with those in a previous study. Heterogeneity was observed among AMLFLT3-ITD patients.

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