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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We sincerely thank the centers of the EBMT for contributing patient information and data collection. Principal investigators of the contributing institutions are listed below.
Principle investigators of the contributing institutions
Sonja Martin15, Patrice Chevallier16, Andreas Neubauer17, Gandhi Damaj18, Yener Koc19, Arnold Ganser20, Matthew Collin21, Ibrahim Yakoub-Agha22, Hakan Ozdogu23, Mercedes Colorado Araujo24, Maija Itäla-Remes25, Kim Orchard26, Cecilia Isaksson27, Wolfgang Bethge28, Hans Martin29, Mahmoud Aljurf30, Edgar Faber31, Dolores Caballero32, Pavel Zák33, Xavier Leleu34, Jacques-Olivier Bay35, Pierre-Simon Rohrlich36, Nicolaus Kröger37, Anne Huynh38, Kerstin Schäfer-Eckart39, Noel Milpied40, Stig Lenhoff41, Aloysius Ho42, Jose Luis Bello López43, Nicola Mordini44, Bruno Lioure45, Kazimierz Halaburda46, Attilio Olivieri47, Tobias Gedde-Dahl48, Rachel Protheroe49, Johanna Tischer50, Matthias Klammer51, Johannes Clausen52, Victoria Potter53, Marco Ladetto54, Herve Tilly55, Eric Deconinck56, Arne Brecht57, Lutz Peter Müller58, Thomas Heinicke59, Juan Pio Torres Carrete60, Ali Bazarbachi61, Péter Reményi62, Marie Thérèse Rubio63, Renato Fanin64, Jose Antonio Pérez-Simón65, Murawski Niels66, J. L. Diez-Martin67, Mutlu Arat68, Olivier Hermine69, Gerard Socié70, Jan J. Cornelissen71, Stella Santarone72, Denis Guyotat73, Claude Eric Bulabois74, Paolo Bernasconi75, Jan-Erik Johansson76, Radovan Vrhovac77, Hildegard Greinix78, José Luis López Lorenzo79, Shashikant Apte80, Charles Craddock81, Guido Kobbe82, Mohsen Al Zahrani83, Peter Dreger84, Andrzej Lange85, Abdelghani Tbakhi86, Ellen Meijer87, Carlos Vallejo Llamas88, Josep Maria Ribera Santasusana89, Paolo Corradini90, Fabio Benedetti91, Alessandro Rambaldi92, Virginie Gandemer93, Jean-Valère Malfuson94, Ain Kaare95, Antonio Risitano96, Mario Petrini97, Carmine Selleri98, Depei Wu99.
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Giebel, S., Labopin, M., Sobczyk-Kruszelnicka, M. 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 Transplant 56, 481–491 (2021). https://doi.org/10.1038/s41409-020-01050-7