U Thiel1, A Wawer1, P Wolf2, M Badoglio3, A Santucci4, T Klingebiel5, O Basu5, A Borkhardt6, H-J Laws6, Y Kodera7, A Yoshimi8, C Peters9, R Ladenstein9, A Pession10, A Prete10, E-C Urban11, W Schwinger11, P Bordigoni12, A Salmon12, M A Diaz13, B Afanasyev14, I Lisukov14, E Morozova14, A Toren15, B Bielorai15, J Korsakas16, F Fagioli17, D Caselli18, G Ehninger19, B Gruhn20, U Dirksen21, F Abdel-Rahman22, M Aglietta23, E Mastrodicasa4, M Torrent24, P Corradini25, F Demeocq26, G Dini27, P Dreger28, M Eyrich29, J Gozdzik30, F Guilhot31, E Holler32, E Koscielniak33, C Messina34, D Nachbaur35, R Sabbatini36, E Oldani37, H Ottinger38, H Ozsahin39, R Schots40, S Siena41, J Stein42, S Sufliarska43, A Unal44, M Ussowicz45, P Schneider46, W Woessmann47, H Jürgens21, M Bregni48, S Burdach49. 1. Department of Pediatrics and Wilhelm Sander Sarcoma Unit MRI, Pediatric Oncology Center, Technische Universität München. 2. Institute for Medical Statistics and Epidemiology, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany. 3. EBMT Data & Study Office, Hopital Saint-Antoine, Assistance Publique des Hôpitaux de Paris and UPMC Univ Paris 06, Paris, France. 4. Section of Pediatric Hematology & Oncology, University of Perugia, Perugia, Italy. 5. Children's Hospital III, Department of Pediatrics, Johann Wolfgang Goethe University, Frankfurt. 6. Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich Heine University, Düsseldorf, Germany. 7. Department of Promotion for Blood and Marrow Transplantation, Aichi Medical University, Aichi; APBMT Data Center, Nagoya University School of Medicine, Nagoya, Japan. 8. APBMT Data Center, Nagoya University School of Medicine, Nagoya, Japan. 9. Department of Pediatrics, St. Anna Kinderspital, Vienna, Austria. 10. Department of Scienze Pediatriche Mediche e Chirurgiche, Ospedale S Orsola Malpighi, Bologna, Italy. 11. Department of Pediatrics, Medical University of Graz, Graz, Austria. 12. Service de Transplantation Medullaire, CHU de Nancy Brabois, Vandoeuvre-les-Nancy, France. 13. Department of Pediatrics, Division of Pediatric Hematology-Oncology and Hematopoietic Stem Cell Transplantation and Cell Therapy Unit, Hospital Infantil Universitario Niño Jesus, Madrid, Spain. 14. St. Petersburg State Medical Pavlov University, Ratsa Gorbacheva Memorial Children`s Institute, Department of Hematology and Transplantology, St. Petersburg, Russia. 15. Pediatric Hemato-Oncology Unit, Sheba Medical Center (affiliated to the Sackler Faculty of Medicine), Tel Hashomer, Israel. 16. Department of Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania. 17. Stem Cell Transplantation and Cellular Therapy Unit, Pediatric Onco-Hematology Division, "Regina Margherita" Children's Hospital, Turin. 18. Department of Oncoematologia Pediatrica, Azienda Ospedaliero-Universitaria Meyer, Florence, Italy. 19. Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden. 20. Department of Pediatrics, University of Jena, Jena. 21. Department of Pediatric Hematology and Oncology, University Children's Hospital, Münster, Germany. 22. The Bone Marrow and Stem Cell Transplantation Program, King Hussein Cancer Center, Amman, Jordan. 23. Department of Istituto per la Ricerca e la Cura del Cancro, Turin, Italy. 24. Hospital de la Santa Creu i Sant Pau, Department of Pediatrics, Barcelona, Spain. 25. Department of Hematology - Bone Marrow Transplantation Unit, Istituto Nazionale dei Tumori, University of Milano, Milan, Italy. 26. Centre Hospitalier et Universitaire de Clermont-Ferrand, Service de Pédiatrie B et Unité Bioclinique de Thérapie Cellulaire, Clermont-Ferrand, France. 27. Department of UO Ematologia ed Oncologia Pediatrica, Istituto G Gaslini, Genova, Italy. 28. Department of Internal Medicine V, University of Heidelberg, Heidelberg. 29. Children's Hospital, Department of Paediatric Stem Cell Transplantation, University of Würzburg, Würzburg, Germany. 30. Transplantation Centre, University Children's Hospital, Cracow, Poland. 31. Department of Hematology, University Hospital, Poitiers, France. 32. Department of Hematology and Oncology, University of Regensburg, Regensburg. 33. Department of Pediatrics 5 (Oncology, Hematology, Immunology), Olga Hospital, Klinikum Stuttgart, Stuttgart, Germany. 34. Hemo/Oncology, Department of Pediatrics, Hospital-University of Padova, Padova, Italy. 35. University Hospital of Innsbruck, Internal Medicine V, Department of Hematology and Oncology, Innsbruck, Austria. 36. Department of Oncology, Haematology, and Respiratory Diseases, Policlinico di Modena, Modena. 37. Department of U.S.C. Ematologia, Ospedali Riuniti, Bergamo, Italy. 38. Department of Bone Marrow Transplantation, University Hospital of Essen, Essen, Germany. 39. Paediatric Oncology Unit, University of Geneva Children's Hospital, Geneva, Switzerland. 40. Division of Clinical Hematology and BMT Unit, University Hospital Brussels, Brussels, Belgium. 41. Department of S. C. Divisione Oncologia Falck and S. C. Divisione Anatomia Patologica, Ospedale Niguarda Ca' Granda, Milan, Italy. 42. Bone marrow Transplant Unit, Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel. 43. Bone Marrow Transplantation Unit, Department of Pediatrics, Comenius University Medical School, Bratislava, Slovak Republic. 44. Institutions Erciyes Medical School, Department of Hematology and Oncology, Kapadokya BMT Center, Kayseri, Turkey. 45. Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland. 46. Department of Pediatric Hematology and Oncology, Hôpital Charles Nicolle, Rouen, France. 47. Department of Pediatric Hematology and Oncology, University Hospital, Giessen, Germany. 48. Unit of Medical Oncology, Ospedale San Giuseppe, Milan, Italy. 49. Department of Pediatrics and Wilhelm Sander Sarcoma Unit MRI, Pediatric Oncology Center, Technische Universität München. Electronic address: meta-eicess@lrz.tum.de.
Abstract
BACKGROUND: Outcomes of Ewing tumor (ET) patients treated with allogeneic stem cell transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts. PATIENTS AND METHODS: We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia Pacific Blood and Marrow Transplantation and MetaEICESS registries treated with allo-SCT. Fifty patients received RIC (group A) and 37 patients received HIC (group B). Twenty-four patients received HLA-mismatched grafts and 63 received HLA-matched grafts. RESULTS: Median overall survival was 7.9 months [±1.24, 95% confidence interval (CI) 5.44-10.31] for group A and 4.4 months (±1.06, 95% CI 2.29-6.43) for group B patients (P = 1.3). Death of complications (DOC) occurred in 4 of 50 (0.08) and death of disease (DOD) in 33 of 50 (0.66) group A and in 16 of 37 (0.43) and 17 of 37 (0.46) group B patients, respectively. DOC incidence was decreased (P < 0.01) and DOD/relapse increased (P < 0.01) in group A compared with group B. HLA mismatch was not generally associated with graft-versus-Ewing tumor effect (GvETE). CONCLUSIONS: There was no improvement of survival with RIC compared with HIC due to increased DOD/relapse incidence after RIC despite less DOC incidence. This implicates general absence of a clinically relevant GvETE with current protocols.
BACKGROUND: Outcomes of Ewing tumor (ET) patients treated with allogeneic stem cell transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts. PATIENTS AND METHODS: We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia Pacific Blood and Marrow Transplantation and MetaEICESS registries treated with allo-SCT. Fifty patients received RIC (group A) and 37 patients received HIC (group B). Twenty-four patients received HLA-mismatched grafts and 63 received HLA-matched grafts. RESULTS: Median overall survival was 7.9 months [±1.24, 95% confidence interval (CI) 5.44-10.31] for group A and 4.4 months (±1.06, 95% CI 2.29-6.43) for group B patients (P = 1.3). Death of complications (DOC) occurred in 4 of 50 (0.08) and death of disease (DOD) in 33 of 50 (0.66) group A and in 16 of 37 (0.43) and 17 of 37 (0.46) group B patients, respectively. DOC incidence was decreased (P < 0.01) and DOD/relapse increased (P < 0.01) in group A compared with group B. HLA mismatch was not generally associated with graft-versus-Ewing tumor effect (GvETE). CONCLUSIONS: There was no improvement of survival with RIC compared with HIC due to increased DOD/relapse incidence after RIC despite less DOC incidence. This implicates general absence of a clinically relevant GvETE with current protocols.
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Authors: U Thiel; E Koscielniak; F Blaeschke; T G P Grunewald; M Badoglio; M A Diaz; C Paillard; A Prete; M Ussowicz; P Lang; F Fagioli; P Lutz; G Ehninger; P Schneider; A Santucci; P Bader; B Gruhn; M Faraci; P Antunovic; J Styczynski; W H Krüger; L Castagna; P Rohrlich; M Ouachée-Chardin; A Salmon; C Peters; M Bregni; S Burdach Journal: Br J Cancer Date: 2013-10-22 Impact factor: 7.640
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