International Journal of Hematology

DOI: 10.1007/s12185-017-2340-z Pages: 1-10

Prognostic value of genetic mutations in adolescent and young adults with acute myeloid leukemia

1. Nagoya University Hospital, Center for Advanced Medicine and Clinical Research

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

3. Nagoya University Graduate School of Medicine, Department of Hematology and Oncology

4. Cleveland Clinic, Department of Translational Hematology and Oncology Research, Taussig Cancer Institute

5. Yokohama City University Hospital, Graduate School of Medicine, Department of Pediatrics

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

7. Okayama University Hospital, Department of Pediatrics

8. Mie University Graduate School of Medicine, Department of Pediatrics

9. Tokai University School of Medicine, Department of Laboratory Medicine

10. National Hospital Organization, Osaka National Hospital, Department of Pediatrics

11. Shiga University of Medical Science, Department of Pediatrics

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

13. National Hospital Organization, Kyushu Cancer Center, Department of Pediatrics

14. National Research Institute for Child Health and Development, Department of Pediatric Hematology and Oncology Research

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

16. Kanagawa Children’s Medical Center, Division of Hemato-Oncology and Regenerative Medicine

17. Hyogo Prefectural Kobe Children’s Hospital, Department of Hematology and Oncology

18. Saitama Medical University, Department of Hematology, International Medical Center

19. Kanazawa University

20. Tokyo Metropolitan Ohtsuka Hospital, Division of Hematology

21. Nagasaki University Graduate School of Biomedical Sciences, Department of Hematology, Atomic Bomb Disease Institute

22. Saiseikai Maebashi Hospital, Leukemia Research Center

23. Japanese Red Cross Nagoya First Hospital, Department of Hematology

24. Jikei University School of Medicine, Division of Clinical Oncology and Hematology, Department of Internal Medicine

25. Kanagawa Cancer Center, Department of Hematology

26. Tokyo Medical University, Department of Hematology

27. Sapporo Hokuyu Hospital, Department of Hematology

28. National Hospital Organization Kyushu Cancer Center, Department of Hematology

29. National Defense Medical College, Division of Hematology, Department of Internal Medicine

30. Ichinomiya Municipal Hospital, Division of Hematology

31. Chiba University Hospital, Department of Hematology

32. The University of Tokyo, Cancer Genomics Project, Graduate School of Medicine

33. Kyoto University, Department of Pathology and Tumor Biology, Graduate School of Medicine

34. National Hospital Organization Nagoya Medical Center

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

36. St. Luke’s International Hospital, Department of Pediatrics

37. Tokyo Medical and Dental University, Department of Pediatrics and Developmental Biology

38. Kyoto University, Human Health Sciences

Correspondence to:
Yachiyo Kuwatsuka
Tel: +81-52-744-1957
Email: ykuwatsuka@med.nagoya-u.ac.jp

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Abstract

Clinical outcomes and the genetic background of acute myeloid leukemia (AML) in adolescent and young adults (AYAs) are known to differ in younger children and older adults. To clarify the impact of genetic mutations on clinical outcomes of AYAs with AML, we analyzed data from the JPLSG AML-05 and JALSG AML201 studies. AYAs aged 15–39 years (n = 103) were included. FLT3-ITD, KIT, CEBPA, NRAS, KRAS, WT1, MLL-PTD, and NPM1 mutations were analyzed. Overall survival (OS) of the AYAs was 61% and event-free survival was 38% at 3 years. FLT3-ITD (HR 2.10; 95% CI 1.07–4.12; p = 0.031) and NPM1 (HR 0.24; 95% CI 0.06–1.00; p = 0.050) mutations were associated with risk of overall mortality in multivariate analysis. OS was significantly different according to FLT3-ITD and NPM1 mutation status (p = 0.03). Survival was 100% with NPM1 mutations in the absence of FLT3-ITD and 35% (95% CI 14–57%) with FLT3-ITD in the absence of NPM1 mutations. The OS of AYAs, children (n = 413) and older adults (n = 124) of the AML-05 and AML201 participants were significantly different (p < 0.0001). This is the first report to combine clinical and genetic data of AYA AML from the major Japanese pediatric and adult study groups.

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