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 Koc; A 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

doi:10.1038/s41409-020-01050-7

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

Hematology

Research output: Contribution to journal › Article › Academic › peer-review

13 Citations (Scopus)

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 language	English
Pages (from-to)	481-491
Number of pages	11
Journal	Bone Marrow Transplantation
Volume	56
Issue number	2
DOIs	https://doi.org/10.1038/s41409-020-01050-7
Publication status	Published - Feb 2021

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

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Giebel, S., Labopin, M., Sobczyk-Kruszelnicka, M., Stelljes, M., Byrne, JL., Fegueux, N., Beelen, DW., Rovira, M., Spyridonidis, A., Blaise, D., Bornhäuser, M., Karadogan, I., Savani, BN., Nagler, A., Mohty, M., Martin, S., Chevallier, P., Neubauer, A., Damaj, G., ... Wu, D. (2021). 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, 56(2), 481-491. https://doi.org/10.1038/s41409-020-01050-7

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. In: Bone Marrow Transplantation. 2021 ; Vol. 56, No. 2. pp. 481-491.

@article{251f5a76489e40f19497b348eb88731e,

title = "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",

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.",

author = "S Giebel and M Labopin and M Sobczyk-Kruszelnicka and M Stelljes and JL Byrne and N Fegueux and DW Beelen and M Rovira and A Spyridonidis and D Blaise and M Bornh{\"a}user and I Karadogan and BN Savani and A Nagler and M Mohty and S Martin and P Chevallier and A Neubauer and G Damaj and Y Koc and A Ganser and M Collin and I Yakoub-Agha and H Ozdogu and MC Araujo and M It{\"a}la-Remes and K Orchard and C Isaksson and W Bethge and H Martin and M Aljurf and E Faber and D Caballero and P Z{\'a}k and X Leleu and JO Bay and PS Rohrlich and N Kr{\"o}ger and A Huynh and K Sch{\"a}fer-Eckart and N Milpied and S Lenhoff and A Ho and JLB L{\'o}pez and N Mordini and B Lioure and K Halaburda and A Olivieri and T Gedde-Dahl and R Protheroe and J Tischer and M Klammer and J Clausen and V Potter and M Ladetto and H Tilly and E Deconinck and A Brecht and LP M{\"u}ller and T Heinicke and JPT Carrete and A Bazarbachi and P Rem{\'e}nyi and MT Rubio and R Fanin and JA P{\'e}rez-Sim{\'o}n and M Niels and JL Diez-Martin and M Arat and O Hermine and G Soci{\'e} and Jan Cornelissen and S Santarone and D Guyotat and CE Bulabois and P Bernasconi and JE Johansson and R Vrhovac and H Greinix and JLL Lorenzo and S Apte and C Craddock and G Kobbe and MA Zahrani and P Dreger and A Lange and A Tbakhi and E Meijer and CV Llamas and JMR Santasusana and P Corradini and F Benedetti and A Rambaldi and V Gandemer and JV Malfuson and A Kaare and A Risitano and M Petrini and C Selleri and D Wu",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = feb,

doi = "10.1038/s41409-020-01050-7",

language = "English",

volume = "56",

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Giebel, S, Labopin, M, Sobczyk-Kruszelnicka, M, Stelljes, M, Byrne, JL, Fegueux, N, Beelen, DW, Rovira, M, Spyridonidis, A, Blaise, D, Bornhäuser, M, Karadogan, I, Savani, BN, Nagler, A, Mohty, M, Martin, S, Chevallier, P, Neubauer, A, Damaj, G, Koc, Y, Ganser, A, Collin, M, Yakoub-Agha, I, Ozdogu, H, Araujo, MC, Itäla-Remes, M, Orchard, K, Isaksson, C, Bethge, W, Martin, H, Aljurf, M, Faber, E, Caballero, D, Zák, P, Leleu, X, Bay, JO, Rohrlich, PS, Kröger, N, Huynh, A, Schäfer-Eckart, K, Milpied, N, Lenhoff, S, Ho, A, López, JLB, Mordini, N, Lioure, B, Halaburda, K, Olivieri, A, Gedde-Dahl, T, Protheroe, R, Tischer, J, Klammer, M, Clausen, J, Potter, V, Ladetto, M, Tilly, H, Deconinck, E, Brecht, A, Müller, LP, Heinicke, T, Carrete, JPT, Bazarbachi, A, Reményi, P, Rubio, MT, Fanin, R, Pérez-Simón, JA, Niels, M, Diez-Martin, JL, Arat, M, Hermine, O, Socié, G, Cornelissen, J, Santarone, S, Guyotat, D, Bulabois, CE, Bernasconi, P, Johansson, JE, Vrhovac, R, Greinix, H, Lorenzo, JLL, Apte, S, Craddock, C, Kobbe, G, Zahrani, MA, Dreger, P, Lange, A, Tbakhi, A, Meijer, E, Llamas, CV, Santasusana, JMR, Corradini, P, Benedetti, F, Rambaldi, A, Gandemer, V, Malfuson, JV, Kaare, A, Risitano, A, Petrini, M, Selleri, C & Wu, D 2021, '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, vol. 56, no. 2, pp. 481-491. https://doi.org/10.1038/s41409-020-01050-7

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. / Giebel, S; Labopin, M; Sobczyk-Kruszelnicka, M et al.
In: Bone Marrow Transplantation, Vol. 56, No. 2, 02.2021, p. 481-491.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - 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

AU - Giebel, S

AU - Labopin, M

AU - Sobczyk-Kruszelnicka, M

AU - Stelljes, M

AU - Byrne, JL

AU - Fegueux, N

AU - Beelen, DW

AU - Rovira, M

AU - Spyridonidis, A

AU - Blaise, D

AU - Bornhäuser, M

AU - Karadogan, I

AU - Savani, BN

AU - Nagler, A

AU - Mohty, M

AU - Martin, S

AU - Chevallier, P

AU - Neubauer, A

AU - Damaj, G

AU - Koc, Y

AU - Ganser, A

AU - Collin, M

AU - Yakoub-Agha, I

AU - Ozdogu, H

AU - Araujo, MC

AU - Itäla-Remes, M

AU - Orchard, K

AU - Isaksson, C

AU - Bethge, W

AU - Martin, H

AU - Aljurf, M

AU - Faber, E

AU - Caballero, D

AU - Zák, P

AU - Leleu, X

AU - Bay, JO

AU - Rohrlich, PS

AU - Kröger, N

AU - Huynh, A

AU - Schäfer-Eckart, K

AU - Milpied, N

AU - Lenhoff, S

AU - Ho, A

AU - López, JLB

AU - Mordini, N

AU - Lioure, B

AU - Halaburda, K

AU - Olivieri, A

AU - Gedde-Dahl, T

AU - Protheroe, R

AU - Tischer, J

AU - Klammer, M

AU - Clausen, J

AU - Potter, V

AU - Ladetto, M

AU - Tilly, H

AU - Deconinck, E

AU - Brecht, A

AU - Müller, LP

AU - Heinicke, T

AU - Carrete, JPT

AU - Bazarbachi, A

AU - Reményi, P

AU - Rubio, MT

AU - Fanin, R

AU - Pérez-Simón, JA

AU - Niels, M

AU - Diez-Martin, JL

AU - Arat, M

AU - Hermine, O

AU - Socié, G

AU - Cornelissen, Jan

AU - Santarone, S

AU - Guyotat, D

AU - Bulabois, CE

AU - Bernasconi, P

AU - Johansson, JE

AU - Vrhovac, R

AU - Greinix, H

AU - Lorenzo, JLL

AU - Apte, S

AU - Craddock, C

AU - Kobbe, G

AU - Zahrani, MA

AU - Dreger, P

AU - Lange, A

AU - Tbakhi, A

AU - Meijer, E

AU - Llamas, CV

AU - Santasusana, JMR

AU - Corradini, P

AU - Benedetti, F

AU - Rambaldi, A

AU - Gandemer, V

AU - Malfuson, JV

AU - Kaare, A

AU - Risitano, A

AU - Petrini, M

AU - Selleri, C

AU - Wu, D

PY - 2021/2

Y1 - 2021/2

N2 - 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.

AB - 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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U2 - 10.1038/s41409-020-01050-7

DO - 10.1038/s41409-020-01050-7

M3 - Article

C2 - 32892216

SN - 0268-3369

VL - 56

SP - 481

EP - 491

JO - Bone Marrow Transplantation

JF - Bone Marrow Transplantation

IS - 2

ER -

Giebel S, Labopin M, Sobczyk-Kruszelnicka M, Stelljes M, Byrne JL, Fegueux N 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 Feb;56(2):481-491. doi: 10.1038/s41409-020-01050-7

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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