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
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Giebel, Sebastian | Labopin, Myriam | Sobczyk-Kruszelnicka, Malgorzata | Stelljes, Matthias | Byrne, Jenny | Fegueux, Nathalie | Beelen, Dietrich | Rovira, Montserrat | Spyridonidis, Alexandros | Blaise, Didier | Bornhäuser, Martin | Karadogan, Ihsan | Savani, Bipin | 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 | Itäla-Remes, Maija | Orchard, Kim | Isaksson, Cecilia | Bethge, Wolfgang | Martin, Hans | Aljurf, Mahmoud | Faber, Edgar | Caballero, Dolores | Zák, Pavel | Leleu, Xavier | Bay, Jacques-Olivier | Rohrlich, Pierre-Simon | Kröger, Nicolaus | Huynh, Anne | Schäfer-Eckart, Kerstin | Milpied, Noel | Lenhoff, Stig | Ho, Aloysius | López, 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 | Reményi, Péter | Rubio, Marie Thérèse | Fanin, Renato | Pérez-Simón, Jose Antonio | Niels, Murawski | Diez-Martin, J. | Arat, Mutlu | Hermine, Olivier | Socié, Gerard | Cornelissen, Jan | Santarone, Stella | Guyotat, Denis | Bulabois, Claude Eric | Bernasconi, Paolo | Johansson, Jan-Erik | Vrhovac, Radovan | Greinix, Hildegard | Lorenzo, José Luis López | 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-Valère | Kaare, Ain | Risitano, Antonio | Petrini, Mario | Selleri, Carmine | Wu, Depei
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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.
