Total body irradiation + fludarabine compared to busulfan + fludarabine as “reduced-toxicity conditioning” for patients with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation in first complete remission

The optimal conditioning for patients with acute myeloid leukemia in first complete remission treated with allogeneic hematopoietic cell transplantation (allo-HCT) has not been defined so far. In this retrospective study, we compared two “reduced-toxicity” regimens: intravenous busulfan at a total d...

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Main Authors: Giebel, Sebastian (Author) , Müller, Lutz P. (Author) , Labopin, Myriam (Author) , Sobczyk-Kruszelnicka, Malgorzata (Author) , Stelljes, Matthias (Author) , Byrne, Jenny L. (Author) , Fegueux, Nathalie (Author) , Beelen, Dietrich W. (Author) , Rovira, Montserrat (Author) , Spyridonidis, Alexandros (Author) , Blaise, Didier (Author) , Bornhäuser, Martin (Author) , Karadogan, Ihsan (Author) , Savani, Bipin N. (Author) , Nagler, Arnon (Author) , Mohty, Mohamad (Author) , Dreger, Peter (Author)
Format: Article (Journal)
Language:English
Published: 2021
In: Bone marrow transplantation
Year: 2021, Volume: 56, Issue: 56, Pages: 481–491
ISSN:1476-5365
DOI:10.1038/s41409-020-01050-7
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41409-020-01050-7
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41409-020-01050-7
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Author Notes:a study by the acute leukemia working party of the EBMT$hSebastian Giebel, Myriam Labopin, Malgorzata Sobczyk-Kruszelnicka, Matthias Stelljes, Jenny L. Byrne, Nathalie Fegueux, Dietrich W. Beelen, Montserrat Rovira, Alexandros Spyridonidis, Didier Blaise, Martin Bornhäuser, Ihsan Karadogan, Bipin N. Savani, Arnon Nagler, Mohamad Mohty, Lutz Peter Müller, principal investigators of the contributing institutions
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Summary:The optimal conditioning for patients with acute myeloid leukemia in first complete remission treated with allogeneic hematopoietic cell transplantation (allo-HCT) has not been defined so far. In this retrospective study, we compared two “reduced-toxicity” regimens: intravenous busulfan at a total dose of 9.6 mg/kg (3 days) + fludarabine (Bu3/Flu) and total body irradiation at a dose of 8 Gy + fludarabine (TBI8Gy/Flu). In the entire study cohort (n = 518), the probabilities of overall survival (OS), leukemia-free survival (LFS), relapse and non-relapse mortality (NRM) at 2 years for Bu3/Flu and TBI8Gy/Flu were 62% vs. 72.5% (p = 0.051), 59.5% vs. 65% (p = 0.15), 30% vs. 20% (p = 0.01), and 10% vs. 14% (p = 0.18), respectively. In multivariate model for patients <50 years old, TBI8Gy/Flu was associated with improved LFS (hazard ratio (HR) = 0.5, p = 0.04), OS (HR = 0.31, p = 0.004), and survival free from both graft-versus-host disease and relapse (HR = 0.55, p = 0.03), as well as tendency to reduced risk of relapse (HR = 0.53, p = 0.08). Among patients aged 50 years or older the use of TBI8Gy/Flu was associated with increased incidence of NRM (HR = 3.9, p = 0.0009), with no significant impact on other outcome measures. We conclude that the use of TBI8Gy/Flu as “reduced-toxicity” regimen may be advised in younger patients with AML referred for allo-HCT.
Item Description:Online publiziert: 5. September 2020
Principle investigators of the contributing institutions: Sonja Martin, Patrice Chevallier, Andreas Neubauer, Gandhi Damaj, Yener Koc, Arnold Ganser, Matthew Collin, Ibrahim Yakoub-Agha, Hakan Ozdogu, Mercedes Colorado Araujo, Maija Itäla-Remes, Kim Orchard, Cecilia Isaksson, Wolfgang Bethge, Hans Martin, Mahmoud Aljurf, Edgar Faber, Dolores Caballero, Pavel Zák, Xavier Leleu, Jacques-Olivier Bay, Pierre-Simon Rohrlich, Nicolaus Kröger, Anne Huynh, Kerstin Schäfer-Eckart, Noel Milpied, Stig Lenhoff, Aloysius Ho, Jose Luis Bello López, Nicola Mordini, Bruno Lioure, Kazimierz Halaburda, Attilio Olivieri, Tobias Gedde-Dahl, Rachel Protheroe, Johanna Tischer, Matthias Klammer, Johannes Clausen, Victoria Potter, Marco Ladetto, Herve Tilly, Eric Deconinck, Arne Brecht, Lutz Peter Müller, Thomas Heinicke, Juan Pio Torres Carrete, Ali Bazarbachi, Péter Reményi, Marie Thérèse Rubio, Renato Fanin, Jose Antonio Pérez-Simón, Murawski Niels, J.L. Diez-Martin, Mutlu Arat, Olivier Hermine, Gerard Socié, Jan J. Cornelissen, Stella Santarone, Denis Guyotat, Claude Eric Bulabois, Paolo Bernasconi, Jan-Erik Johansson, Radovan Vrhovac, Hildegard Greinix, José Luis López Lorenzo, Shashikant Apte, Charles Craddock, Guido Kobbe, Mohsen Al Zahrani, Peter Dreger, Andrzej Lange, Abdelghani Tbakhi, Ellen Meijer, Carlos Vallejo Llamas, Josep Maria Ribera Santasusana, Paolo Corradini, Fabio Benedetti, Alessandro Rambaldi, Virginie Gandemer, Jean-Valère Malfuson, Ain Kaare, Antonio Risitano, Mario Petrini, Carmine Selleri, Depei Wu
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Physical Description:Online Resource
ISSN:1476-5365
DOI:10.1038/s41409-020-01050-7