title: 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.
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.
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan. Electronic address: skurosaw@ncc.go.jp.
authors.forename: Saiko
authors.initials: S
authors.lastname: Kurosawa
authors.affiliation: Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Division of Biostatistics, Tohoku University Hospital, Sendai, Japan.
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Fukunaga
authors.affiliation: Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yui
authors.affiliation: Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Wakita
authors.affiliation: Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Heiwa
authors.initials: H
authors.lastname: Kanamori
authors.affiliation: Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Usuki
authors.affiliation: Department of Hematology, Matsushita Memorial Hospital, Moriguchi, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Uoshima
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Yanada
authors.affiliation: Department of Hematology, Chiba Aoba Municipal Hospital, Chiba, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Shono
authors.affiliation: Department of Hematology, Nagano Red Cross Hospital, Nagano, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Ueki
authors.affiliation: Department of Hematology, Hyogo Cancer Center, Akashi, Japan.
authors.forename: Ishikazu
authors.initials: I
authors.lastname: Mizuno
authors.affiliation: Division of Clinical Oncology and Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Yano
authors.affiliation: Department of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Jin
authors.initials: J
authors.lastname: Takeuchi
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Kanda
authors.affiliation: Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamura
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Inamoto
authors.affiliation: Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Koiti
authors.initials: K
authors.lastname: Inokuchi
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukuda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D060830:Consolidation Chemotherapy / Q000592:standards*; D020732:Cytogenetic Analysis; D003661:Decision Support Techniques; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000592:standards*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000628:therapy*; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011788:Quality of Life; D012074:Remission Induction; D018570:Risk Assessment; D014184:Transplantation, Homologous; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D051941:fms-Like Tyrosine Kinase 3
keywords: Acute myeloid leukemia; Decision analysis; Hematopoietic cell transplantation; Quality of life