Arnon Nagler1, Bipin N Savani2, Myriam Labopin3, Emmanuelle Polge3, Jakob Passweg4, Jürgen Finke5, Slawomira Kyrcz-Krzemien6, Liisa Volin7, Achilles Anagnostopoulos8, Mahmoud Aljurf9, Dietrich W Beelen10, Stephane Vigouroux11, Noel Milpied11, Felipe Suarez12, Mohamad Mohty3. 1. Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel; European Group for Blood and Marrow Transplantation (EBMT) Paris Study Office/CEREST-TC, Paris, France. 2. Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: bipin.savani@vanderbilt.edu. 3. 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. 4. University Hospital, Basel, Switzerland. 5. Department of Medicine, Division of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg, Freiburg, Germany. 6. University Department of Haematology and BMT, Medical University of Silesia, Katowice, Poland. 7. Helsinki University Central Hospital, Comprehensive Cancer Center, Helsinki, Finland. 8. Haematology Department/BMT Unit, George Papanicolaou General Hospital, Thessaloniki, Greece. 9. Department of Oncology, Section of Adult Haematology/BMT, King Faisal Specialist Hospital and Research Centre Riyadh, Saudi Arabia. 10. Department of Bone Marrow Transplantation, University Hospital, Essen, Germany. 11. Department of Haematology and Cell Therapy, University Hospital, Bordeaux, France. 12. Department of Adult Hematology, Necker University Hospital, INSERM U1163, Institut Imagine, Sorbonne Paris Cité and Université Paris Descartes, Paris, France.
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. FINDINGS: 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%]). INTERPRETATION: 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. FUNDING: None.
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. FINDINGS: 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%]). INTERPRETATION: 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. FUNDING: None.
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