title: High WT1 expression is an early predictor for relapse in patients with acute promyelocytic leukemia in first remission with negative PML-RARa after anthracycline-based chemotherapy: a single-center cohort study.
abstract: Wilms' tumor gene 1 (WT1) expression is a well-known predictor for relapse in acute myeloid leukemia. We monitored WT1 decrement along the treatment course to identify its significant role as a marker for residual disease in acute promyelocytic leukemia (APL) and tried to suggest its significance for relapse prediction. In this single center retrospective study, we serially measured PML-RARa and WT1 expression from 117 APL patients at diagnosis, at post-induction and post-consolidation chemotherapies, and at every 3 months after starting maintenance therapy. All 117 patients were in molecular remission after treatment of at least 2 consolidation chemotherapies. We used WT1 ProfileQuant™ kit (Ipsogen) for WT1 monitoring. High WT1 expression (>120 copies/104ABL1) after consolidation and at early period (3 months) after maintenance therapy significantly predicted subsequent relapse. All paired PML-RARa RQ-PCR were not detected except for one sample with early relapse. Patients with high WT1 expression at 3 months after maintenance therapy (n = 40) showed a significantly higher relapse rate (30.5 vs. 6.9%, P < 0.001) and inferior disease free survival (62.8 vs. 91.4%, P < 0.001). Multivariate analysis revealed that high peak leukocyte counts at diagnosis (HR = 6.4, P < 0.001) and high WT1 expression at 3 months after maintenance therapy (HR = 7.1, P < 0.001) were significant factors for prediction of relapse. Our data showed high post-remission WT1 expression was a reliable marker for prediction of subsequent molecular relapse in APL. In this high-risk group, early intervention with ATRA ± ATO, anti-CD33 antibody therapy, and WT1-specific therapy may be used for relapse prevention.
  
  
  
  Clinical Research Information Service (CRIS), KCT0002079.
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Korea. cumckim@catholic.ac.kr.
authors.forename: Hee-Je
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Korea.
authors.forename: Dae-Hun
authors.initials: DH
authors.lastname: Kwak
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Korea.
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Park
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Korea.
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Jeon
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Korea.
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Korea.
authors.forename: Byung-Sik
authors.initials: BS
authors.lastname: Cho
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Korea.
authors.forename: Ki-Seong
authors.initials: KS
authors.lastname: Eom
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Korea.
authors.forename: Yoo-Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Korea.
authors.forename: Seok
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Korea.
authors.forename: Chang-Ki
authors.initials: CK
authors.lastname: Min
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Korea.
authors.forename: Seok-Goo
authors.initials: SG
authors.lastname: Cho
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Korea.
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Korea.
authors.forename: Jong Wook
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Korea.
authors.forename: Woo-Sung
authors.initials: WS
authors.lastname: Min
mesh_terms: D018943:Anthracyclines / Q000627:therapeutic use*; D000906:Antibodies / Q000627:therapeutic use; D015331:Cohort Studies; D018572:Disease-Free Survival; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D007958:Leukocyte Count; D018365:Neoplasm, Residual / Q000175:diagnosis*; D015514:Oncogene Proteins, Fusion / Q000032:analysis; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000276:immunology; D014212:Tretinoin / Q000627:therapeutic use; D025721:WT1 Proteins / Q000032:analysis / Q000235:genetics*
chemical_list: D018943:Anthracyclines; D000906:Antibodies; C571163:CD33 protein, human; D015514:Oncogene Proteins, Fusion; D063268:Sialic Acid Binding Ig-like Lectin 3; D025721:WT1 Proteins; C583751:WT1 protein, human; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin
keywords: Acute promyelocytic leukemia; FLT3 mutation; Minimal residual disease; WT1