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

Sebastian Giebel , Myriam Labopin , Malgorzata Sobczyk-Kruszelnicka , Matthias Stelljes , Jenny Byrne , Nathalie Fegueux , Dietrich Beelen , Montserrat Rovira , Alexandros Spyridonidis , Didier Blaise (1, 2) , Martin Bornhäuser , Ihsan Karadogan , Bipin Savani , Arnon Nagler , Mohamad Mohty , 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. Diez-Martin , Mutlu Arat , Olivier Hermine , Gerard Socié , Jan 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

1 IPC - Institut Paoli-Calmettes
2 CRCM - Centre de Recherche en Cancérologie de Marseille

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.

Domaines: Cancer; Immunologie

Sebastian Giebel, Myriam Labopin, Malgorzata Sobczyk-Kruszelnicka, Matthias Stelljes, Jenny Byrne, et al.. 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. Bone Marrow Transplantation, 2021, 56 (2), pp.481-491. ⟨10.1038/s41409-020-01050-7⟩. ⟨hal-03623714⟩