BACKGROUND: The role of allogeneic stem cell transplantation in post-remission management of children with high-risk acute myeloid leukemia remains controversial. In the multi-center AML-BFM 98 study we prospectively evaluated the impact of allogeneic stem cell transplantation in children with high-risk acute myeloid leukemia in first complete remission. DESIGN AND METHODS: HLA-typed patients with high-risk acute myeloid leukemia, who achieved first complete remission (n = 247), were included in this analysis. All patients received double induction and consolidation. Based on the availability of a matched-sibling donor, patients were allocated by genetic chance to allogeneic stem cell transplantation (n = 61) or chemotherapy-only (i.e. intensification and maintenance therapy; n = 186). The main analysis was done on an intention-to-treat basis according to this allocation. RESULTS: Intention-to-treat analysis did not show a significantly different 5-year disease-free survival (49 ± 6% versus 45 ± 4%, P(log rank) = 0.44) or overall survival (68 ± 6% versus 57 ± 4%, P(log rank) = 0.17) between the matched-sibling donor and no-matched-sibling donor groups, whereas late adverse effects occurred more frequently after allogeneic stem cell transplantation (72.5% versus 31.8%, P(Fischer)<0.01). These results were confirmed by as-treated analysis corrected for the time until transplantation (5-year overall survival: 72 ± 8% versus 60 ± 4%, P(Mantel-Byar) 0.21). Subgroup analysis demonstrated improved survival rates for patients with 11q23 aberrations allocated to allogeneic stem cell transplantation (5-year overall survival: 94 ± 6% versus 52 ± 7%, P(log-rank) = 0.01; n = 18 versus 49) in contrast to patients without 11q23 aberrations (5-year overall survival: 58 ± 8% versus 55 ± 5%, P(log-rank) = 0.66). CONCLUSIONS: Our analyses defined a genetic subgroup of children with high-risk acute myeloid leukemia who benefited from allogeneic stem cell transplantation in the prospective multi-center AML-BFM 98 study. For the remainder of the pediatric high-risk acute myeloid leukemia patients the prognosis was not improved by allogeneic stem cell transplantation, which was, however, associated with a higher rate of late sequelae.
RCT Entities:
BACKGROUND: The role of allogeneic stem cell transplantation in post-remission management of children with high-risk acute myeloid leukemia remains controversial. In the multi-center AML-BFM 98 study we prospectively evaluated the impact of allogeneic stem cell transplantation in children with high-risk acute myeloid leukemia in first complete remission. DESIGN AND METHODS: HLA-typed patients with high-risk acute myeloid leukemia, who achieved first complete remission (n = 247), were included in this analysis. All patients received double induction and consolidation. Based on the availability of a matched-sibling donor, patients were allocated by genetic chance to allogeneic stem cell transplantation (n = 61) or chemotherapy-only (i.e. intensification and maintenance therapy; n = 186). The main analysis was done on an intention-to-treat basis according to this allocation. RESULTS: Intention-to-treat analysis did not show a significantly different 5-year disease-free survival (49 ± 6% versus 45 ± 4%, P(log rank) = 0.44) or overall survival (68 ± 6% versus 57 ± 4%, P(log rank) = 0.17) between the matched-sibling donor and no-matched-sibling donor groups, whereas late adverse effects occurred more frequently after allogeneic stem cell transplantation (72.5% versus 31.8%, P(Fischer)<0.01). These results were confirmed by as-treated analysis corrected for the time until transplantation (5-year overall survival: 72 ± 8% versus 60 ± 4%, P(Mantel-Byar) 0.21). Subgroup analysis demonstrated improved survival rates for patients with 11q23 aberrations allocated to allogeneic stem cell transplantation (5-year overall survival: 94 ± 6% versus 52 ± 7%, P(log-rank) = 0.01; n = 18 versus 49) in contrast to patients without 11q23 aberrations (5-year overall survival: 58 ± 8% versus 55 ± 5%, P(log-rank) = 0.66). CONCLUSIONS: Our analyses defined a genetic subgroup of children with high-risk acute myeloid leukemia who benefited from allogeneic stem cell transplantation in the prospective multi-center AML-BFM 98 study. For the remainder of the pediatric high-risk acute myeloid leukemiapatients the prognosis was not improved by allogeneic stem cell transplantation, which was, however, associated with a higher rate of late sequelae.
Authors: A Sander; M Zimmermann; M Dworzak; G Fleischhack; C von Neuhoff; D Reinhardt; G J L Kaspers; U Creutzig Journal: Leukemia Date: 2010-06-10 Impact factor: 11.528
Authors: Denise M Oliansky; J Douglas Rizzo; Peter D Aplan; Robert J Arceci; Louis Leone; Yaddanapudi Ravindranath; Jean E Sanders; Franklin O Smith; Fiona Wilmot; Philip L McCarthy; Theresa Hahn Journal: Biol Blood Marrow Transplant Date: 2007-01 Impact factor: 5.742
Authors: B E S Gibson; K Wheatley; I M Hann; R F Stevens; D Webb; R K Hills; S S N De Graaf; C J Harrison Journal: Leukemia Date: 2005-12 Impact factor: 11.528
Authors: Christine von Neuhoff; Dirk Reinhardt; Annette Sander; Martin Zimmermann; Jutta Bradtke; David R Betts; Zuzana Zemanova; Jan Stary; Jean-Pierre Bourquin; Oskar A Haas; Michael N Dworzak; Ursula Creutzig Journal: J Clin Oncol Date: 2010-05-03 Impact factor: 44.544
Authors: Y Ravindranath; M Chang; C P Steuber; D Becton; G Dahl; C Civin; B Camitta; A Carroll; S C Raimondi; H J Weinstein Journal: Leukemia Date: 2005-12 Impact factor: 11.528
Authors: Ursula Creutzig; Martin Zimmermann; Thomas Lehrnbecher; Norbert Graf; Johann Hermann; Charlotte M Niemeyer; Alfred Reiter; Jörg Ritter; Michael Dworzak; Jan Stary; Dirk Reinhardt Journal: J Clin Oncol Date: 2006-09-20 Impact factor: 44.544
Authors: A Pession; R Rondelli; G Basso; C Rizzari; A M Testi; F Fagioli; P De Stefano; F Locatelli Journal: Leukemia Date: 2005-12 Impact factor: 11.528
Authors: John T Horan; Todd A Alonzo; Gary H Lyman; Robert B Gerbing; Beverly J Lange; Yaddanapudi Ravindranath; David Becton; Franklin O Smith; William G Woods Journal: J Clin Oncol Date: 2008-10-27 Impact factor: 44.544
Authors: Beverly J Lange; Franklin O Smith; James Feusner; Dorothy R Barnard; Patricia Dinndorf; Stephen Feig; Nyla A Heerema; Carola Arndt; Robert J Arceci; Nita Seibel; Margie Weiman; Kathryn Dusenbery; Kevin Shannon; Sandra Luna-Fineman; Robert B Gerbing; Todd A Alonzo Journal: Blood Date: 2007-11-13 Impact factor: 22.113
Authors: Brian V Balgobind; Susana C Raimondi; Jochen Harbott; Martin Zimmermann; Todd A Alonzo; Anne Auvrignon; H Berna Beverloo; Myron Chang; Ursula Creutzig; Michael N Dworzak; Erik Forestier; Brenda Gibson; Henrik Hasle; Christine J Harrison; Nyla A Heerema; Gertjan J L Kaspers; Anna Leszl; Nathalia Litvinko; Luca Lo Nigro; Akira Morimoto; Christine Perot; Rob Pieters; Dirk Reinhardt; Jeffrey E Rubnitz; Franklin O Smith; Jan Stary; Irina Stasevich; Sabine Strehl; Takashi Taga; Daisuke Tomizawa; David Webb; Zuzana Zemanova; C Michel Zwaan; Marry M van den Heuvel-Eibrink Journal: Blood Date: 2009-06-15 Impact factor: 22.113
Authors: G Michel; R Cunha; A Ruggeri; T A O'Brien; H Bittencourt; J H Dalle; F Locatelli; A P Iori; M Mauad; C Oudin; F Giannotti; F Volt; E Gluckman; P Bader; V Rocha Journal: Leukemia Date: 2015-09-15 Impact factor: 11.528
Authors: Colin de Haar; Maud Plantinga; Nina Jg Blokland; Niek P van Til; Thijs Wh Flinsenberg; Viggo F Van Tendeloo; Evelien L Smits; Louis Boon; Lotte Spel; Marianne Boes; Jaap Jan Boelens; Stefan Nierkens Journal: Oncoimmunology Date: 2015-05-27 Impact factor: 8.110
Authors: Martin G Sauer; Peter J Lang; Michael H Albert; Peter Bader; Ursula Creutzig; Matthias Eyrich; Johann Greil; Bernd Gruhn; Wolfgang Holter; Thomas Klingebiel; Bernhard Kremens; Heiko von der Leyen; Christine Mauz-Körholz; Roland Meisel; Kirsten Mischke; Ingo Müller; Charlotte M Niemeyer; Christina Peters; Christine Pohler; Dirk Reinhardt; Birgit Burkhardt; Paul G Schlegel; Ansgar S Schulz; Johanna Schrum; Petr Sedlacek; Brigitte Strahm; Wilhelm Woessmann; Rupert Handgretinger; Martin Zimmermann; Arndt Borkhardt Journal: Leukemia Date: 2019-10-02 Impact factor: 11.528
Authors: Michael J Kelly; John T Horan; Todd A Alonzo; Mary Eapen; Robert B Gerbing; Wensheng He; Beverly J Lange; Susan K Parsons; William G Woods Journal: Pediatr Blood Cancer Date: 2013-08-19 Impact factor: 3.167
Authors: F Locatelli; R Masetti; R Rondelli; M Zecca; F Fagioli; A Rovelli; C Messina; E Lanino; A Bertaina; C Favre; G Giorgiani; M Ripaldi; O Ziino; G Palumbo; M Pillon; A Pession; S Rutella; A Prete Journal: Bone Marrow Transplant Date: 2014-11-10 Impact factor: 5.483
Authors: A Sureda; P Bader; S Cesaro; P Dreger; R F Duarte; C Dufour; J H F Falkenburg; D Farge-Bancel; A Gennery; N Kröger; F Lanza; J C Marsh; A Nagler; C Peters; A Velardi; M Mohty; A Madrigal Journal: Bone Marrow Transplant Date: 2015-03-23 Impact factor: 5.483
Authors: A-L Alloin; G Leverger; J-H Dalle; C Galambrun; Y Bertrand; A Baruchel; A Auvrignon; V Gandemer; C Ragu; A Loundou; C Bilhou-Nabera; M Lafage-Pochitaloff; N Dastugue; B Nelken; C Jubert; F Rialland; G Plat; C Pochon; J-P Vannier; P-S Rohrlich; J Kanold; P Lutz; A Sirvent; C Oudin; W Cuccuini; G Michel Journal: Bone Marrow Transplant Date: 2016-12-12 Impact factor: 5.483
Authors: Elad Jacoby; Allen Chen; David M Loeb; Christopher J Gamper; Elias Zambidis; Nicolas J Llosa; Jeffrey Huo; Kenneth R Cooke; Rick Jones; Ephraim Fuchs; Leo Luznik; Heather J Symons Journal: Biol Blood Marrow Transplant Date: 2015-09-04 Impact factor: 5.742