title: Serial measurement of WT1 expression and decrement ratio until hematopoietic cell transplantation as a marker of residual disease in patients with cytogenetically normal acute myelogenous leukemia.
abstract: Using real-time quantitative PCR, we monitored Wilms tumor gene 1 (WT1) expression from diagnosis to hematopoietic stem cell transplantation (HSCT) in adult patients with cytogenetically normal acute myelogenous leukemia (CN-AML) and FLT3-ITD and NPM1 mutations. The values at diagnosis were evaluated in 104 patients. Data collected after induction chemotherapy were available for all patients, but only 68 patients were treated with HSCT. Significant WT1 expression cut-offs were determined by receiver operation characteristic curve analysis, and rates of overall survival (OS) and disease-free survival (DFS) were estimated. WT1 decrement ratios (DR) at postinduction chemotherapy and at pre- and post-HSCT compared with the diagnostic level were calculated. Higher WT1 expression at diagnosis, postinduction chemotherapy, and pre-HSCT showed inferior OS (P = .015, <.001, and .002) and DFS (P = .006, <.001, and .003). The cut-offs were determined at the median for diagnostic WT1 expression and at the 25% level from the top for other time points excluding post-HSCT. The WT1 DR ≥ 1-log after induction chemotherapy showed superior OS and DFS (P = .009 and .002) and WT1 DR ≥ 1-log preceding HSCT also showed superior OS and DFS (P = .009 and .003). Results of WT1 DR were consistently applicable in each subgroup with higher (≥ 1.0) and lower (<1.0) WT1 expression at diagnosis and also in NPM1-wild-type/FLT3-ITD-negative CN-AML. The WT1 DR therefore predicted survival outcomes after HSCT more accurately than did the diagnostic WT1 expression. WT1 expression may serve as a reliable marker for residual disease and WT1 DR as a prognostic indicator, particularly in NPM1-wild-type/FLT3-ITD-negative CN-AML. These measures may be applied throughout the course of treatment and even after HSCT.
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Yoon
authors.forename: Hee-Je
authors.initials: HJ
authors.lastname: Kim
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Shin
authors.forename: Seung-Ah
authors.initials: SA
authors.lastname: Yahng
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Byung-Sik
authors.initials: BS
authors.lastname: Cho
authors.forename: Ki-Seong
authors.initials: KS
authors.lastname: Eom
authors.forename: Yoo-Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Seok
authors.initials: S
authors.lastname: Lee
authors.forename: Chang-Ki
authors.initials: CK
authors.lastname: Min
authors.forename: Seok-Goo
authors.initials: SG
authors.lastname: Cho
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Lee
authors.forename: Woo-Sung
authors.initials: WS
authors.lastname: Min
authors.forename: Chong-Won
authors.initials: CW
authors.lastname: Park
authors.forename: Ji-Hyang
authors.initials: JH
authors.lastname: Lim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology*; D020732:Cytogenetic Analysis; D005260:Female; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality / Q000628:therapy; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology; D000090243:Nucleophosmin; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000276:immunology; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D025721:WT1 Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D014408:Biomarkers, Tumor; D019653:Myeloablative Agonists; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D025721:WT1 Proteins; C583751:WT1 protein, human; D000090243:Nucleophosmin