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Giebel, Sebastian; Labopin, Myriam; Sobczyk-Kruszelnicka, Malgorzata; Stelljes, Matthias; Byrne, Jenny L.; Fegueux, Nathalie; Beelen, Dietrich W.; Rovira, Montserrat; Spyridonidis, Alexandros; Blaise, Didier; Bornhaeuser, Martin; Karadogan, Ihsan; Savani, Bipin N.; Nagler, Arnon; Mohty, Mohamad; Martin, Sonja; Chevallier, Patrice; Neubauer, Andreas; Damaj, Gandhi; Koc, Yener; Ganser, Arnold; Collin, Matthew; Yakoub-Agha, Ibrahim; Ozdogu, Hakan; Araujo, Mercedes Colorado; Itala-Remes, Maija; Orchard, Kim; Isaksson, Cecilia; Bethge, Wolfgang; Martin, Hans; Aljurf, Mahmoud; Faber, Edgar; Caballero, Dolores; Zak, Pavel; Leleu, Xavier; Bay, Jacques-Olivier; Rohrlich, Pierre-Simon; Kroeger, Nicolaus; Huynh, Anne; Schaefer-Eckart, Kerstin; Milpied, Noel; Lenhoff, Stig; Ho, Aloysius; Lopez, Jose Luis Bello; Mordini, Nicola; Lioure, Bruno; Halaburda, Kazimierz; Olivieri, Attilio; Gedde-Dahl, Tobias; Protheroe, Rachel; Tischer, Johanna; Klammer, Matthias; Clausen, Johannes; Potter, Victoria; Ladetto, Marco; Tilly, Herve; Deconinck, Eric; Brecht, Arne; Müller, Lutz Peter; Heinicke, Thomas; Carrete, Juan Pio Torres; Bazarbachi, Ali; Remenyi, Peter; Rubio, Marie Therese; Fanin, Renato; Perez-Simon, Jose Antonio; Niels, Murawski; Diez-Martin, J. L.; Arat, Mutlu; Hermine, Olivier; Socie, Gerard; Cornelissen, Jan J.; Santarone, Stella; Guyotat, Denis; Bulabois, Claude Eric; Bernasconi, Paolo; Johansson, Jan-Erik; Vrhovac, Radovan; Greinix, Hildegard; Lorenzo, Jose Luis Lopez; Apte, Shashikant; Craddock, Charles; Kobbe, Guido; Zahrani, Mohsen Al; Dreger, Peter; Lange, Andrzej; Tbakhi, Abdelghani; Meijer, Ellen; Llamas, Carlos Vallejo; Santasusana, Josep Maria Ribera; Corradini, Paolo; Benedetti, Fabio; Rambaldi, Alessandro; Gandemer, Virginie; Malfuson, Jean-Valere; Kaare, Ain; Risitano, Antonio; Petrini, Mario; Selleri, Carmine; Wu, Depei (2020): Total body irradiation plus fludarabine compared to busulfan plus fludarabine as "reduced-toxicity conditioning" for patients with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation in first complete remission: a study by the Acute Leukemia Working Party of the EBMT. In: Bone Marrow Transplantation, Vol. 56, No. 2: pp. 481-491
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Abstract

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.

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