ORIGINAL ARTICLE High-dose chemotherapy (HDCT) with auto-SCT in children with atypical teratoid/rhabdoid tumors (AT/RT): a report from the European Rhabdoid Registry (EU-RHAB) M Benesch 1 , K Bartelheim 2 , G Fleischhack 3 , B Gruhn 4 , PG Schlegel 5 , O Witt 6 , KD Stachel 7 , H Hauch 8 , C Urban 1 , F Quehenberger 9 , M Massimino 10 , T Pietsch 11 , M Hasselblatt 12 , F Giangaspero 13,14 , U Kordes 15 , R Schneppenheim 15 , P Hauser 16 , T Klingebiel 17 and MC Fru¨ hwald 2,18 A retrospective analysis of data from the European Rhabdoid Registry (EU-RHAB) was performed to describe the outcome of children with atypical teratoid/rhabdoid tumors (AT/RT) who underwent high-dose chemotherapy (HDCT) with auto-SCT. Nineteen patients (male, n ¼ 15; median age at diagnosis 21 months) were identified. Nine patients presented with metastatic disease at diagnosis. A partial or subtotal resection was achieved in 11, a total resection in five and a biopsy in three patients. Patients received a median of six chemotherapy cycles prior to HDCT. Additional radiotherapy was performed in 14 patients (first-line, n ¼ 9; following progression, n ¼ 5). Six patients underwent tandem auto-SCT. Disease status before HDCT was CR in six, PR in eight, stable disease in two and progressive disease (PD) in two patients (data missing, n ¼ 1). With a median follow-up of 16 months, 14 patients progressed. Estimated progression-free and OS at 2 years were 29% ( ± 11%) and 50% ( ± 12%), respectively. At last follow-up, eight patients were alive (first CR, n ¼ 4; second CR, n ¼ 2; PR, n ¼ 1; PD, n ¼ 1). Eleven patients died of PD. Median time-to-progression was 14 months. Selected patients with AT/RT might benefit from HDCT with radiotherapy. The definitive impact of this treatment modality has to be evaluated prospectively in a randomized trial. Bone Marrow Transplantation (2014) 49, 370–375; doi:10.1038/bmt.2013.208; published online 13 January 2014 Keywords: atypical teratoid/rhabdoid tumors; auto-SCT; children INTRODUCTION Atypical teratoid/rhabdoid tumors (AT/RT) are highly malignant tumors of the central nervous system (CNS). 1 Among children below the age of 3 years, AT/RT constitute the most common malignant CNS tumors (17.3%), followed by medulloblastomas (16%) and primitive neuroectodermal tumors of the CNS (13.3%). 2 In a population-based study, the age-standardized incidence rate of AT/RT was calculated at 1.38 per 1 000 000 person–years. 2 The median age at diagnosis is between 14 and 24 months, with boys more commonly affected than girls. 1–9 Infratentorial location has been reported in 38–65% of AT/RT and up to 1/3 of patients with AT/RT present with metastatic disease at diagnosis. 1–9 Prognosis of patients with AT/RT is generally poor. The vast majority of patients develop early local progression or recurren- ce ± distant metastases within 1 year following diagnosis. 1–8 Among various clinical parameters, younger age and presence of metastases were most consistently associated with a worse outcome. 4,5–7,9 In terms of treatment, a gross total resection 2,4,5,8 and radiotherapy 5,6,9 seem to contribute to a prolongation of survival. The impact of high-dose chemotherapy (HDCT) with auto-SCT on prognosis is unclear. The aim of the present retrospective analysis was thus to report the clinical characteristics and outcome of 19 children with AT/RT who underwent HDCT within the European Rhabdoid Registry (EU-RHAB) and the previous registry Rhabdoid 2007. PATIENTS AND METHODS Aims of EU-RHAB and rhabdoid 2007 The primary goal of the EU-RHAB registry is to optimize the management of patients with rhabdoid tumors of all anatomical sites. Thus EU-RHAB serves as a platform for the standardized registration of epidemiologic-, molecular-, clinical- and treatment-related data. EU-RHAB contains 1 Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria; 2 Swabian Children’s Cancer Center, Children’s Hospital Augsburg, Augsburg, Germany; 3 Pediatrics III, University Hospital of Essen, Essen, Germany; 4 Department of Pediatrics, Jena University Hospital, Jena, Germany; 5 Department of Pediatric Hematology, Oncology and Neurooncology, University Children’s Hospital Wu¨ rzburg, Wu¨ rzburg, Germany; 6 Department of Pediatric Oncology, Hematology, Immunology and Pneumonology, Children’s Hospital, University of Heidelberg, Heidelberg, Germany; 7 Children’s University Hospital, Friedrich-Alexander University Erlangen-Nu¨ rnberg, Erlangen, Germany; 8 Department of Pediatric Hematology and Oncology, Justus Liebig University Gieen, Gieen, Germany; 9 Institute for Medical Statistics, Medical University of Graz, Graz, Austria; 10 Department of Pediatrics, Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy; 11 Institute of Neuropathology, University of Bonn, Bonn, Germany; 12 Institute of Neuropathology, University Hospital Mu¨ nster, Mu¨ nster, Germany; 13 Department of Radiological, Oncological and Anatomo-pathological Sciences, University La Sapienza, Rome, Italy; 14 IRCCS Neuromed, Pozzilli, Italy; 15 Department of Pediatric Hematology and Oncology, University Medical Center Hamburg- Eppendorf, Hamburg, Germany; 16 Department of Pediatrics, Semmelweis University, Budapest, Hungary; 17 Division of Pediatric Hematology and Oncology, Department of Pediatrics, J. W. Goethe University Children’s Hospital of Frankfurt, Frankfurt, Germany and 18 Department of Pediatric Hematology and Oncology, University Children’s Hospital Mu¨ nster, Mu¨ nster, Germany. Correspondence: Dr M Benesch, Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Auenbruggerplatz 38, A-8036 Graz, Austria or Dr MC Fru¨ hwald, Swabian Children’s Cancer Center, Children’s Hospital Augsburg, Stenglinstrae 2, D-86156 Augsburg, Germany. E-mail: martin.benesch@klinikum-graz.at or michael.fruehwald@klinikum-augsburg.de Received 9 July 2013; revised 12 November 2013; accepted 12 November 2013; published online 13 January 2014 Bone Marrow Transplantation (2014) 49, 370–375 & 2014 Macmillan Publishers Limited All rights reserved 0268-3369/14 www.nature.com/bmt