title: Outcomes after use of two standard ablative regimens in patients with refractory acute myeloid leukaemia: a retrospective, multicentre, registry analysis.
abstract: BACKGROUND
  Cyclophosphamide plus intravenous busulfan has not been compared with cyclophosphamide plus total body irradiation (TBI) in adults with advanced refractory acute myeloid leukaemia before allogeneic haemopoietic stem-cell transplantation (HCT). We aimed to assess whether survival of patients receiving ablative intravenous busulfan-based conditioning regimens before a related or volunteer-unrelated donor HCT for refractory acute myeloid leukaemia is not inferior to that of patients receiving an ablative TBI-based regimen.
  
  
  METHODS
  In this retrospective, multicentre, registry-based study, we obtained data for patients (aged >18 years) with refractory acute myeloid leukaemia in active phase of disease, who had received HCT from an HLA-identical sibling or an unrelated donor after intravenous busulfan plus cyclophosphamide or cyclophosphamide plus TBI conditioning between 2000 and 2012. Data was obtained from the European Group for Blood and Marrow Transplantation registry. The primary endpoints of the study were overall survival and leukaemia-free survival.
  
  
  RESULTS
  We obtained data for 514 patients who had received intravenous busulfan plus cyclophosphamide and 338 patients who had received cyclophosphamide plus TBI. The median percentage of blasts before HCT did not differ significantly between groups (20% [range 5-100; IQR 10-32] in the intravenous busulfan plus cyclophosphamide group vs 16% [5-95; 9-33] in the cyclophosphamide plus TBI group; p=0·16). Overall survival at 2 years did not differ between the groups in the univariate analysis (31·2% [95% CI 26·8-35·5] with intravenous busulfan plus cyclophosphamide vs 33·4% [28·1-38·7] wth cyclophosphamide plus TBI; p=0·65). Leukaemia-free survival at 2 years also did not differ between groups (25·0% [95% CI 21·0-29·0] vs 28·4% [23·4-33·5]; p=0·47). In multivariable analysis adjusting for differences between both groups, no difference was noted between the two groups in terms of overall survival (hazard ratio [HR] 0·99 [95% CI 0·83-1·20]; p=0·95) or leukaemia-free survival (HR 0·97 [0·81-1·16]; p=0·71). Main causes of non-relapse mortality were graft-versus-host disease (49 [10%] in the intravenous busulfan plus cyclophosphamide group vs 25 [7%] in the cyclophosphamide plus TBI group) and infection (36 [7%] vs 18 [5%]).
  
  
  CONCLUSIONS
  From a practical standpoint, the use of intravenous busulfan plus cyclophosphamide is likely to be a valid and efficient alternative to cyclophosphamide plus TBI conditioning regimen for patients with refractory acute myeloid leukaemia, especially for those transplant centres without access to radiation facilities.
  
  
  BACKGROUND
  None.
authors.affiliation: Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel; European Group for Blood and Marrow Transplantation (EBMT) Paris Study Office/CEREST-TC, Paris, France.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: bipin.savani@vanderbilt.edu.
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.affiliation: European Group for Blood and Marrow Transplantation (EBMT) Paris Study Office/CEREST-TC, Paris, France; Department of Haematology, Saint Antoine Hospital, Paris, France; INSERM UMR 938, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: European Group for Blood and Marrow Transplantation (EBMT) Paris Study Office/CEREST-TC, Paris, France; Department of Haematology, Saint Antoine Hospital, Paris, France; INSERM UMR 938, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Polge
authors.affiliation: University Hospital, Basel, Switzerland.
authors.forename: Jakob
authors.initials: J
authors.lastname: Passweg
authors.affiliation: Department of Medicine, Division of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg, Freiburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Finke
authors.affiliation: University Department of Haematology and BMT, Medical University of Silesia, Katowice, Poland.
authors.forename: Slawomira
authors.initials: S
authors.lastname: Kyrcz-Krzemien
authors.affiliation: Helsinki University Central Hospital, Comprehensive Cancer Center, Helsinki, Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Volin
authors.affiliation: Haematology Department/BMT Unit, George Papanicolaou General Hospital, Thessaloniki, Greece.
authors.forename: Achilles
authors.initials: A
authors.lastname: Anagnostopoulos
authors.affiliation: Department of Oncology, Section of Adult Haematology/BMT, King Faisal Specialist Hospital and Research Centre Riyadh, Saudi Arabia.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Aljurf
authors.affiliation: Department of Bone Marrow Transplantation, University Hospital, Essen, Germany.
authors.forename: Dietrich W
authors.initials: DW
authors.lastname: Beelen
authors.affiliation: Department of Haematology and Cell Therapy, University Hospital, Bordeaux, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Vigouroux
authors.affiliation: Department of Haematology and Cell Therapy, University Hospital, Bordeaux, France.
authors.forename: Noel
authors.initials: N
authors.lastname: Milpied
authors.affiliation: Department of Adult Hematology, Necker University Hospital, INSERM U1163, Institut Imagine, Sorbonne Paris Cité and Université Paris Descartes, Paris, France.
authors.forename: Felipe
authors.initials: F
authors.lastname: Suarez
authors.affiliation: European Group for Blood and Marrow Transplantation (EBMT) Paris Study Office/CEREST-TC, Paris, France; Department of Haematology, Saint Antoine Hospital, Paris, France; INSERM UMR 938, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D002066:Busulfan / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012042:Registries; D012189:Retrospective Studies; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D014916:Whole-Body Irradiation; D055815:Young Adult
chemical_list: D003520:Cyclophosphamide; D002066:Busulfan