title: Wilms' tumor gene 1 transcript levels in leukapheresis of peripheral blood hematopoietic cells predict relapse risk in patients autografted for acute myeloid leukemia.
abstract: Autologous hematopoietic stem cell transplantation (ASCT) is a curative option alternative to allogeneic transplantation for patients with acute myeloid leukemia (AML). Relapse after ASCT can be due to contamination with leukemic blasts of autologous peripheral blood stem cells (PBSCs) collected by leukapheresis (LK). Identification and quantification of a minimal residual disease (MRD) marker in PBSCs could be relevant in determining the relapse risk after ASCT. High levels of the WT1 gene transcript in bone marrow of AML patients after treatment completion predict disease relapse. We evaluated WT1 transcript levels in autologous PBSC from LK used for ASCT in 30 consecutive AML patients in complete remission (CR) and established a correlation with clinical outcome. At diagnosis, all patients had WT1 overexpression. All patients were in morphological and genetic CR at the time of PBSC collection and before ASCT. Real-time quantitative PCR of WT1 was performed in samples of each LK, using TaqMan technology on RNA from mononucleated cells. The median WT1 transcript level in the PBSC graft (WT1-LK) of patients who relapsed was significantly higher than of those who did not relapse after transplantation (P <.0001). We defined a cut-off level of 80 WT1-LK copies/ABL 10e4 copies to discriminate between positive and negative PBSC grafts. The cut-off level was strongly associated with disease recurrence, DFS and OS. Our study represents the largest series of patients evaluating WT1 as a marker of MRD in PBSC LK products using a completely standardized real-time WT1-reverse transcriptase-PCR based assay. These data, if confirmed by prospective study, will help to determine an individual patient's adapted postremission allocation strategy.
authors: Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors: Carlo
authors: C
authors: Messina
authors: Division of Hematology and Bone Marrow Transplantation Unit, University Hospital of Udine, Udine, Italy.
authors: Anna
authors: A
authors: Candoni
authors: Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors: Matteo G
authors: MG
authors: Carrabba
authors: Immuno-hematology and Transfusion Medicine, San Raffaele Scientific Institute, Milan, Italy.
authors: Cristina
authors: C
authors: Tresoldi
authors: Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors: Elisa
authors: E
authors: Sala
authors: Immuno-hematology and Transfusion Medicine, San Raffaele Scientific Institute, Milan, Italy.
authors: Michela
authors: M
authors: Tassara
authors: Immuno-hematology and Transfusion Medicine, San Raffaele Scientific Institute, Milan, Italy.
authors: Alessandra
authors: A
authors: Crippa
authors: Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors: Jacopo
authors: J
authors: Peccatori
authors: Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors: Andrea
authors: A
authors: Assanelli
authors: Immuno-hematology and Transfusion Medicine, San Raffaele Scientific Institute, Milan, Italy.
authors: Salvatore
authors: S
authors: Gattillo
authors: Immuno-hematology and Transfusion Medicine, San Raffaele Scientific Institute, Milan, Italy.
authors: Laura
authors: L
authors: Bellio
authors: Division of Hematology and Bone Marrow Transplantation Unit, University Hospital of Udine, Udine, Italy.
authors: Renato
authors: R
authors: Fanin
authors: Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy. Electronic address: ciceri.fabio@hsr.it.
authors: Fabio
authors: F
authors: Ciceri
authors: Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors: Massimo
authors: M
authors: Bernardi
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007937:Leukapheresis; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D018365:Neoplasm, Residual; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D025721:WT1 Proteins / Q000235:genetics* / Q000276:immunology
chemical_list: D014408:Biomarkers, Tumor; D019653:Myeloablative Agonists; D012333:RNA, Messenger; D025721:WT1 Proteins; C583751:WT1 protein, human
keywords: Acute myeloid leukemia; Autologous stem cell transplantation; Minimal residual disease; Peripheral blood stem cell apheresis; Real-time quantitative PCR; Wilms' tumor gene 1