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: a study by the Acute Leukemia Working Party of the EBMT

S Giebel, M Labopin, M Sobczyk-Kruszelnicka, M Stelljes, JL Byrne, N Fegueux, DW Beelen, M Rovira, A Spyridonidis, D Blaise, M Bornhäuser, I Karadogan, BN Savani, A Nagler, M Mohty, S Martin, P Chevallier, A Neubauer, G Damaj, Y KocA Ganser, M Collin, I Yakoub-Agha, H Ozdogu, MC Araujo, M Itäla-Remes, K Orchard, C Isaksson, W Bethge, H Martin, M Aljurf, E Faber, D Caballero, P Zák, X Leleu, JO Bay, PS Rohrlich, N Kröger, A Huynh, K Schäfer-Eckart, N Milpied, S Lenhoff, A Ho, JLB López, N Mordini, B Lioure, K Halaburda, A Olivieri, T Gedde-Dahl, R Protheroe, J Tischer, M Klammer, J Clausen, V Potter, M Ladetto, H Tilly, E Deconinck, A Brecht, LP Müller, T Heinicke, JPT Carrete, A Bazarbachi, P Reményi, MT Rubio, R Fanin, JA Pérez-Simón, M Niels, JL Diez-Martin, M Arat, O Hermine, G Socié, Jan Cornelissen, S Santarone, D Guyotat, CE Bulabois, P Bernasconi, JE Johansson, R Vrhovac, H Greinix, JLL Lorenzo, S Apte, C Craddock, G Kobbe, MA Zahrani, P Dreger, A Lange, A Tbakhi, E Meijer, CV Llamas, JMR Santasusana, P Corradini, F Benedetti, A Rambaldi, V Gandemer, JV Malfuson, A Kaare, A Risitano, M Petrini, C Selleri, D Wu

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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.

Original languageEnglish
Pages (from-to)481-491
Number of pages11
JournalBone Marrow Transplantation
Volume56
Issue number2
DOIs
Publication statusPublished - Feb 2021

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© 2020, The Author(s), under exclusive licence to Springer Nature Limited.

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