title: Effective use of high-dose chemotherapy and autologous stem cell rescue for relapsed adult Wilms' tumor and a novel alteration in intron 1 of the WT1 gene.
abstract: Adult Wilms' tumor (AWT) is a very rare and aggressive malignancy, and little information is available on effective therapy in adults. Although mutations in WT1 have been found in 10% to 15% of childhood Wilms' tumor patients, to date WT1 mutations in AWT patients have not been described. The authors describe a 47-year-old man with relapsed AWT and a novel germline alteration in intron 1 of WT1: IVS1-6 C-->A. This alteration may reduce the splicing efficiency for exon 2 and possibly results in exon skipping. The effective salvage chemotherapy contained ifosfamide, carboplatin, and etoposide and was followed by a high-dose chemotherapy that contained melphalan, carboplatin, and etoposide. Both chemotherapy regimens showed moderate treatment-related toxicity. This report is the first that indicates that adult nephroblastoma patients also may carry WT1 germline mutations.
authors.affiliation: Department of Hematology and Oncology, Charité University Hospital Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, D-13353 Berlin, Germany. ralf_ulrich.trappe@charite.de
authors.forename: Ralf Ulrich
authors.initials: RU
authors.lastname: Trappe
authors.forename: Hanno
authors.initials: H
authors.lastname: Riess
authors.forename: Frank
authors.initials: F
authors.lastname: Lippek
authors.forename: Michail
authors.initials: M
authors.lastname: Plotkin
authors.forename: Valerie
authors.initials: V
authors.lastname: Schumacher
authors.forename: Brigitte
authors.initials: B
authors.lastname: Royer-Pokora
authors.forename: Bert
authors.initials: B
authors.lastname: Hildebrandt
authors.forename: Johannes
authors.initials: J
authors.lastname: Zuber
authors.forename: Markus Y
authors.initials: MY
authors.lastname: Mapara
authors.forename: Stephan
authors.initials: S
authors.lastname: Oertel
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D016162:Genes, Wilms Tumor; D018095:Germ-Line Mutation; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D016879:Salvage Therapy; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D009396:Wilms Tumor / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D005047:Etoposide; D016190:Carboplatin; D008558:Melphalan