Total body irradiation plus fludarabine versus busulfan plus fludarabine as a myeloablative conditioning for adults with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation. A study on behalf of the Acute Leukemia Working Party of the EBMT.
Journal
Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
23
05
2022
accepted:
18
11
2022
revised:
16
11
2022
pubmed:
3
12
2022
medline:
15
3
2023
entrez:
2
12
2022
Statut:
ppublish
Résumé
Cyclophosphamide is frequently substituted with fludarabine (Flu) in conditioning regimens before allogeneic hematopoietic cell transplantation (allo-HCT). We aimed to compare retrospectively, total body irradiation (12 Gy) plus Flu (FluTBI12) versus busulfan (Bu) plus Flu (FB4) as a myeloablative conditioning before allo-HCT in patients with acute myeloid leukemia (AML). Out of 3203 patients who met the inclusion criteria, 109 patients treated with FluTBI12 and 213 treated with FB4 were included in a final matched-pair analysis. In both groups, median patient age was 41 years, first or second complete remission (CR1/CR2) proportion was 78%/22%, allo-HCT from an unrelated donor was performed in 78% of patients. The probabilities of leukemia-free survival and overall survival at 2 years in FluTBI12 and FB4 groups were 65% vs. 60% (p = 0.64) and 70% vs. 72% (p = 0.87), respectively. The cumulative incidence of relapse was 19% vs. 29% (p = 0.11), while non-relapse mortality was 16% vs. 11%, respectively (p = 0.13). There were no statistical differences in both acute and chronic graft-versus-host disease (GVHD) incidence. The probability of GVHD-free, relapse-free survival (GRFS) was 49% for both groups. FluTBI12 and FB4 are comparable myeloablative regimens before allo-HCT in AML patients transplanted in CR1 and CR2.
Identifiants
pubmed: 36460819
doi: 10.1038/s41409-022-01882-5
pii: 10.1038/s41409-022-01882-5
doi:
Substances chimiques
Busulfan
G1LN9045DK
fludarabine
P2K93U8740
Vidarabine
FA2DM6879K
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
282-287Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Nagler A, Rocha V, Labopin M, Unal A, Ben Othman T, Campos A, et al. Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in remission: comparison of intravenous busulfan plus cyclophosphamide (Cy) versus total-body irradiation plus Cy as conditioning regimen-a report from the acute leukemia working party of the European group for blood and marrow transplantation. J Clin Oncol. 2013;31:3549–56.
doi: 10.1200/JCO.2013.48.8114
pubmed: 23980086
Nagler A, Savani BN, Labopin M, Polge E, Passweg J, Finke J, et al. Outcomes after use of two standard ablative regimens in patients with refractory acute myeloid leukaemia: a retrospective, multicentre, registry analysis. Lancet Haematol. 2015;2:e384–e392.
doi: 10.1016/S2352-3026(15)00146-5
pubmed: 26685771
Ben-Barouch S, Cohen O, Vidal L, Avivi I, Ram R. Busulfan fludarabine vs busulfan cyclophosphamide as a preparative regimen before allogeneic hematopoietic cell transplantation: systematic review and meta-analysis. Bone Marrow Transpl. 2016;51:232–40.
doi: 10.1038/bmt.2015.238
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 Transpl. 2021;56:481–91.
doi: 10.1038/s41409-020-01050-7
Solomon SR, Solh M, Zhang X, Morris LE, Holland HK, Bashey A. Fludarabine and total-body irradiation conditioning before ablative haploidentical transplantation: long-term safety and efficacy. Biol Blood Marrow Transpl. 2019;25:2211–6.
doi: 10.1016/j.bbmt.2019.06.017
Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, et al. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015;16:1525–36.
doi: 10.1016/S1470-2045(15)00200-4
pubmed: 26429297
Kanate AS, Nagler A, Savani B. Summary of scientific and statistical methods, study endpoints and definitions for observational and registry-based studies in hematopoietic cell transplantation. Clin Hematol Int. 2020;2:2–4.
doi: 10.2991/chi.d.191207.001
pubmed: 34595436
Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med. 1999;18:695–706.
doi: 10.1002/(SICI)1097-0258(19990330)18:6<695::AID-SIM60>3.0.CO;2-O
pubmed: 10204198
Fine JP, Gray RJ. A proportional hazards model for subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.
doi: 10.1080/01621459.1999.10474144
Giebel S, Miszczyk L, Slosarek K, Moukhtari L, Ciceri F, Esteve J, et al. Extreme heterogeneity of myeloablative total body irradiation techniques in clinical practice: a survey of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Cancer. 2014;120:2760–5.
doi: 10.1002/cncr.28768
pubmed: 24804873
Fog LS, Wirth A, MacManus M, Downes S, Grace M, Moggré A, et al. Total body irradiation in Australia and New Zealand: results of a practice survey. Phys Eng Sci Med. 2020;43:825–35.
doi: 10.1007/s13246-020-00878-z
pubmed: 32613526
Atkinson JB, Mahoney FJ, Schwartz IR, Hesch JA. Therapy of acute leukemia by whole-body irradiation and bone marrow transplantation from an identical normal twin. Blood. 1959;14:228–34.
doi: 10.1182/blood.V14.3.228.228
pubmed: 13628820
Belkacemi Y, Labopin M, Giebel S, Loganadane G, Miszczyk L, Michallet M, et al. Single-dose daily fractionation is not inferior to twice-a-day fractionated total-body irradiation before allogeneic stem cell transplantation for acute leukemia: a useful practice simplification resulting from the SARASIN study. Int J Radiat Oncol Biol Phys. 2018;102:515–26.
doi: 10.1016/j.ijrobp.2018.06.015
pubmed: 29928948
Ueda N, Konuma T, Aoki J, Takahashi S, Ozawa Y, Mori T, et al. Prognostic impact of the fractionation of total body irradiation for patients with acute myeloid leukemia undergoing myeloablative allogeneic hematopoietic cell transplantation. Transpl Cell Ther. 2021;27:185.e1–185.e6.
doi: 10.1016/j.jtct.2020.10.018
Blaise D, Maraninchi D, Archimbaud E, Reiffers J, Devergie A, Jouet JP, et al. Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: a randomized trial of a busulfan-Cytoxan versus Cytoxan-total body irradiation as preparative regimen: a report from the Group d’Etudes de la Greffe de Moelle Osseuse. Blood. 1992;79:2578–82.
doi: 10.1182/blood.V79.10.2578.bloodjournal79102578
pubmed: 1586710
Stelljes M, Bornhauser M, Kroger M, Beyer J, Sauerland MC, Heinecke A, et al. Conditioning with 8-Gy total body irradiation and fludarabine for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia. Blood. 2005;106:3314–21.
doi: 10.1182/blood-2005-04-1377
pubmed: 16020510
Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, et al. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012;13:1035–44.
doi: 10.1016/S1470-2045(12)70349-2
pubmed: 22959335
Ciurea SO, Andersson BS. Busulfan in hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2009;15:523–36.
doi: 10.1016/j.bbmt.2008.12.489
Liu H, Zhai X, Song Z, Sun J, Xiao Y, Nie D, et al. Busulfan plus fludarabine as a myeloablative conditioning regimen compared with busulfan plus cyclophosphamide for acute myeloid leukemia in first complete remission undergoing allogeneic hematopoietic stem cell transplantation: a prospective and multicenter study. J Hematol Oncol. 2013;6:15.
doi: 10.1186/1756-8722-6-15
pubmed: 23394705
pmcid: 3571894
Dholaria B, Labopin M, Angelucci E, Ciceri F, Diez-Martin JL, Bruno B, et al. Impact of total body irradiation- vs chemotherapy-based myeloablative conditioning on outcomes of haploidentical hematopoietic cell transplantation for acute myelogenous leukemia. Am J Hematol. 2020;95:1200–8.
doi: 10.1002/ajh.25934