Etoposide plus cytarabine versus cyclophosphamide or melphalan in busulfan-based preparative regimens for autologous stem cell transplantation in adults with acute myeloid leukemia in first complete remission: a study from the Acute Leukemia Working Party of the EBMT.
Humans
Adult
Hematopoietic Stem Cell Transplantation
Melphalan
/ therapeutic use
Busulfan
Etoposide
/ therapeutic use
Cytarabine
/ therapeutic use
Retrospective Studies
Transplantation, Autologous
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Leukemia, Myeloid, Acute
/ drug therapy
Cyclophosphamide
/ therapeutic use
Acute Disease
Transplantation Conditioning
Journal
Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
received:
25
05
2023
accepted:
25
07
2023
revised:
13
07
2023
medline:
6
11
2023
pubmed:
9
8
2023
entrez:
8
8
2023
Statut:
ppublish
Résumé
We retrospectively compared the impact of the conditioning regimen in adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) that received high-dose myeloablative chemotherapy followed by autologous stem cell transplantation (ASCT) from 2010 to 2021 with either high-dose cytarabine, etoposide and busulfan (BEA), busulfan with cyclophosphamide (BUCY) or busulfan and high-dose melphalan (BUMEL) registered in the EBMT database. Overall 1560 patients underwent ASCT, of which 156, 1143 and 261 received BEA, BUCY and BUMEL, respectively. Compared to BUCY and BUMEL, BEA patients were younger (p < 0.001) and less frequently had NPM1 mutations (p = 0.03). Transplant outcomes at 5 years with BEA, BUCY and BUMEL were: cumulative incidence of relapse 41.8%, 46.6% and 51.6%; non-relapse mortality (NRM) 1.5%, 5.2% and 7.3%; probability of leukemia-free survival (LFS) 56.7%, 48.2% and 41.1%; and overall survival (OS) 71.3%, 62.3% and 56%, respectively. In multivariable analysis the BEA regimen showed significant improvement in OS compared to BUCY (hazard ratio [HR] 0.65; 95% CI, 0.42-0.83; p = 0.048) and BUMEL (HR 0.59; 95% CI, 0.37-0.94; p = 0.029). In conclusion, high-dose myeloablative combination chemotherapy with BEA offered improved outcomes compared to classical BUCY or BUMEL in patients with AML in CR1 undergoing ASCT.
Identifiants
pubmed: 37553468
doi: 10.1038/s41409-023-02075-4
pii: 10.1038/s41409-023-02075-4
doi:
Substances chimiques
Melphalan
Q41OR9510P
Busulfan
G1LN9045DK
Etoposide
6PLQ3CP4P3
Cytarabine
04079A1RDZ
Cyclophosphamide
8N3DW7272P
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1197-1202Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Döhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140:1345–77.
doi: 10.1182/blood.2022016867
pubmed: 35797463
Snowden JA, Sánchez-Ortega I, Corbacioglu S, Basak GW, Chabannon C, de la Camara R, et al. Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2022. Bone Marrow Transplant. 2022;57:1217–39.
doi: 10.1038/s41409-022-01691-w
pubmed: 35589997
pmcid: 9119216
Gorin N-C, Labopin M, Czerw T, Pabst T, Blaise D, Dumas P-Y, et al. Autologous stem cell transplantation for adult acute myelocytic leukemia in first remission-Better outcomes after busulfan and melphalan compared with busulfan and cyclophosphamide: a retrospective study from the Acute Leukemia Working Party of the Europe. Cancer. 2017;123:824–31.
doi: 10.1002/cncr.30400
pubmed: 27906458
Gorin NC, Labopin M, Blaise D, Dumas PY, Pabst T, Trisolini SM, et al. Optimizing the pretransplant regimen for autologous stem cell transplantation in acute myelogenous leukemia: Better outcomes with busulfan and melphalan compared with busulfan and cyclophosphamide in high risk patients autografted in first complete remiss. Am J Hematol. 2018;93:859–66.
doi: 10.1002/ajh.25105
pubmed: 29644709
Harada M, Akashi K, Hayashi S, Eto T, Takamatsu Y, Teshima T, et al. Granulocyte colony-stimulating factor-combined marrow-ablative chemotherapy and autologous blood cell transplantation for the treatment of patients with acute myelogenous leukemia in first remission. Int J Hematol. 1997;66:297–301.
doi: 10.1016/S0925-5710(97)00037-6
pubmed: 9401275
Gondo H, Harada M, Miyamoto T, Takenaka K, Tanimoto K, Mizuno S, et al. Autologous peripheral blood stem cell transplantation for acute myelogenous leukemia. Bone Marrow Transplant. 1997;20:821–6.
doi: 10.1038/sj.bmt.1700979
pubmed: 9404921
Moscardó F, Mediavilla JD, de la Rubia J, Fernández P, Rayón C, Cañigral G, et al. 18: Autologous peripheral blood stem cell transplant using busulfan, etoposide, high dose Ara-C, and G-CSF priming as conditioning regimen in patients with acute myeloid leukemia in first complete remission. Biol. Blood Marrow Transplant. 2007;13:9.
doi: 10.1016/j.bbmt.2006.12.021
Eto T, Takase K, Miyamoto T, Ohno Y, Kamimura T, Nagafuji K, et al. Autologous peripheral blood stem cell transplantation with granulocyte colony-stimulating factor combined conditioning regimen as a postremission therapy for acute myelogenous leukemia in first complete remission. Int J Hematol. 2013;98:186–96.
doi: 10.1007/s12185-013-1378-9
pubmed: 23754766
Miyamoto T, Nagafuji K, Fujisaki T, Uchida N, Matsue K, Henzan H, et al. Prospective randomization of post-remission therapy comparing autologous peripheral blood stem cell transplantation versus high-dose cytarabine consolidation for acute myelogenous leukemia in first remission. Int J Hematol. 2018;107:468–77.
doi: 10.1007/s12185-017-2389-8
pubmed: 29243031
Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010;116:354–65.
doi: 10.1182/blood-2009-11-254441
pubmed: 20385793
Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.
doi: 10.1080/01621459.1999.10474144
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
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.
doi: 10.1080/01621459.1958.10501452
Cox DR. Regression models and life tables (with discussion). J R Stat Soc B. 1972;34:187–220.
Biard L, Labopin M, Chevret S, Resche-Rigon M. Investigating covariate-by-centre interaction in survival data. Stat Methods Med Res. 2018;27:920–32.
doi: 10.1177/0962280216647981
pubmed: 27166409
Passweg JR, Baldomero H, Chabannon C, Basak GW, Corbacioglu S, Duarte R, et al. The EBMT activity survey on hematopoietic-cell transplantation and cellular therapy 2018: CAR-T’s come into focus. Bone Marrow Transplant. 2020;55:1604–13.
doi: 10.1038/s41409-020-0826-4
pubmed: 32066864
pmcid: 7391287
Shouval R, Labopin M, Bomze D, Baerlocher GM, Capria S, Blaise D, et al. Risk stratification using FLT3 and NPM1 in acute myeloid leukemia patients autografted in first complete remission. Bone Marrow Transplantation. 2020;55:2244–53.
doi: 10.1038/s41409-020-0936-z
pubmed: 32388535
Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, et al. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011;118:6037–42.
doi: 10.1182/blood-2011-07-370247
pubmed: 21951683
Eter P, Assileth AC, Arrington APH, Rederick F, Ppelbaum RA, Azarus IML, et al. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med. 1998;339:1649–56. https://doi.org/10.1056/NEJM199812033392301 .
doi: 10.1056/NEJM199812033392301
Keating A, DaSilva G, Pérez WS, Gupta V, Cutler CS, Ballen KK, et al. Autologous blood cell transplantation versus HLA-identical sibling transplantation for acute myeloid leukemia in first complete remission: a registry study from the center for international blood and marrow transplantation research. Haematologica. 2013;98:185–92.
doi: 10.3324/haematol.2012.062059
pubmed: 22983587
pmcid: 3561424
Schlenk RF, Taskesen E, van Norden Y, Krauter J, Ganser A, Bullinger L, et al. The value of allogeneic and autologous hematopoietic stem cell transplantation in prognostically favorable acute myeloid leukemia with double mutant CEBPA. Blood. 2013;122:1576–82.
doi: 10.1182/blood-2013-05-503847
pubmed: 23863898
Mizutani M, Hara M, Fujita H, Aoki J, Kanamori H, Ohashi K, et al. Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR. Bone Marrow Transplant. 2016;51:645–53.
doi: 10.1038/bmt.2015.349
pubmed: 26808566
Baron F, Efficace F, Cannella L, Willemze R, Vignetti M, Muus P, et al. Long-term follow-up of a trial comparing post-remission treatment with autologous or allogeneic bone marrow transplantation or intensive chemotherapy in younger acute myeloid leukemia patients. Haematologica. 2020;105:E13–6.
doi: 10.3324/haematol.2019.221333
pubmed: 31097634
pmcid: 6939505
Lemoli RM, D’addio A, Marotta G, Pezzullo L, Zuffa E, Montanari M, et al. BU/melphalan and auto-SCT in AML patients in first CR: a ‘Gruppo Italiano Trapianto di Midollo Osseo (GITMO)’ retrospective study. Bone Marrow Transplantation. 2010;45:640–6.
doi: 10.1038/bmt.2009.235
pubmed: 19802019