TY - JOUR
T1 - Decision Analysis of Postremission Therapy in Cytogenetically Intermediate-Risk Acute Myeloid Leukemia
T2 - The Impact of FLT3 Internal Tandem Duplication, Nucleophosmin, and CCAAT/Enhancer Binding Protein Alpha
AU - Kurosawa, Saiko
AU - Yamaguchi, Hiroki
AU - Yamaguchi, Takuhiro
AU - Fukunaga, Keiko
AU - Yui, Shunsuke
AU - Wakita, Satoshi
AU - Kanamori, Heiwa
AU - Usuki, Kensuke
AU - Uoshima, Nobuhiko
AU - Yanada, Masamitsu
AU - Shono, Katsuhiro
AU - Ueki, Toshimitsu
AU - Mizuno, Ishikazu
AU - Yano, Shingo
AU - Takeuchi, Jin
AU - Kanda, Junya
AU - Okamura, Hiroshi
AU - Inamoto, Yoshihiro
AU - Inokuchi, Koiti
AU - Fukuda, Takahiro
N1 - Funding Information:
The authors thank all the physicians who provided leukemia samples and clinical data. The results were presented at the 56th Annual Meeting of the American Society of Hematology in San Francisco, CA, on December 6, 2014. Financial disclosure statement: This work was supported by grants from the National Cancer Research and Development Fund (26-A-26) and the Advanced Clinical Research Organization . Conflict of interest statement: The authors declare no conflicts of interest. Authorship contribution statement : S.K. was the principal investigator and takes primary responsibility for the manuscript; H.Y. was primarily responsible for the laboratory work in this study and interpreted data; T.Y. was primarily responsible for the study design, data analysis, and interpretation of the data; K.F., S.Yui, and S.W. performed laboratory work in this study; H.K., K.U., N.U., M.Y., K.S., T.U., I.M., S.Yano, J.T., J.K., and H.O. provided leukemia samples and clinical data and interpreted data; Y.I. helped to analyze and interpret data; and K.I. and T.F. interpreted data.
Publisher Copyright:
© 2016 The American Society for Blood and Marrow Transplantation.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
KW - Acute myeloid leukemia
KW - Decision analysis
KW - Hematopoietic cell transplantation
KW - Quality of life
UR - http://www.scopus.com/inward/record.url?scp=84973358567&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84973358567&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2016.03.015
DO - 10.1016/j.bbmt.2016.03.015
M3 - Article
C2 - 27040395
AN - SCOPUS:84973358567
SN - 1083-8791
VL - 22
SP - 1125
EP - 1132
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 6
ER -
