Decision Analysis of Postremission Therapy in Cytogenetically Intermediate-Risk Acute Myeloid Leukemia: The Impact of FLT3 Internal Tandem Duplication, Nucleophosmin, and CCAAT/Enhancer Binding Protein Alpha

Saiko Kurosawa, Hiroki Yamaguchi, Takuhiro Yamaguchi, Keiko Fukunaga, Shunsuke Yui, Satoshi Wakita, Heiwa Kanamori, Kensuke Usuki, Nobuhiko Uoshima, Masamitsu Yanada, Katsuhiro Shono, Toshimitsu Ueki, Ishikazu Mizuno, Shingo Yano, Jin Takeuchi, Junya Kanda, Hiroshi Okamura, Yoshihiro Inamoto, Koiti Inokuchi, Takahiro Fukuda

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We performed a decision analysis comparing allogeneic hematopoietic cell transplantation (allo-HCT) versus chemotherapy in first complete remission for patients with cytogenetically intermediate-risk acute myeloid leukemia, depending on the presence or absence of FLT3-internal tandem duplication (ITD), nucleophosmin (NPM1), and CCAAT/enhancer binding protein alpha (CEBPA) mutations. Adjusted means of the patient-reported EQ-5D index were used as quality-of-life (QOL) estimates. In 332 patients for which FLT3-ITD status was available, FLT3-ITD was present in 60. In 272 patients without FLT3-ITD, NPM1 mutations were present in 83. CEBPA biallelic mutations were detected in 53 patients. For patients harboring FLT3-ITD, allo-HCT improved life expectancy (LE) (52 versus 32 months during 10-year observation) and QOL-adjusted life expectancy (QALE, 36 versus 21). Monte-Carlo simulation identified allo-HCT as the favored strategy in 100% of simulations. In patients without FLT3-ITD, allo-HCT improved LE/QALE with or without NPM1 mutations. However, sensitivity analyses showed that the results were not robust enough. For patients harboring CEBPA biallelic mutations, chemotherapy was favored (LE, 53 versus 84; QALE, 37 versus 59), whereas, for patients with monoallelic mutations or wild-type CEBPA, allo-HCT was favored (LE, 68 versus 54; QALE, 48 versus 37). Sensitivity analyses did not change the results in either group. In conclusion, based on a Markov decision analysis, allo-HCT was a favored postremission strategy in patients with FLT3-ITD, and chemotherapy was favored in patients with biallelic CEBPA mutations. A prospective study is warranted to determine the value of allo-HCT, especially in FLT3-ITD-negative patients.

Original languageEnglish
Pages (from-to)1125-1132
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume22
Issue number6
DOIs
Publication statusPublished - 2016 Jun 1

Keywords

  • Acute myeloid leukemia
  • Decision analysis
  • Hematopoietic cell transplantation
  • Quality of life

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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    Kurosawa, S., Yamaguchi, H., Yamaguchi, T., Fukunaga, K., Yui, S., Wakita, S., Kanamori, H., Usuki, K., Uoshima, N., Yanada, M., Shono, K., Ueki, T., Mizuno, I., Yano, S., Takeuchi, J., Kanda, J., Okamura, H., Inamoto, Y., Inokuchi, K., & Fukuda, T. (2016). Decision Analysis of Postremission Therapy in Cytogenetically Intermediate-Risk Acute Myeloid Leukemia: The Impact of FLT3 Internal Tandem Duplication, Nucleophosmin, and CCAAT/Enhancer Binding Protein Alpha. Biology of Blood and Marrow Transplantation, 22(6), 1125-1132. https://doi.org/10.1016/j.bbmt.2016.03.015