Arnon Nagler1, Vanderson Rocha, Myriam Labopin, Ali Unal, Tarek Ben Othman, Antonio Campos, Liisa Volin, Xavier Poire, Mahmoud Aljurf, Tamás Masszi, Gerard Socie, Henrik Sengelov, Mauricette Michallet, Jakob Passweg, Hendrik Veelken, Ibrahim Yakoub-Agha, Avichai Shimoni, Mohamad Mohty. 1. Arnon Nagler and Avichai Shimoni, Chaim Sheba Medical Center, Tel Hasomer, Israel; Vanderson Rocha, Churchill Hospital, Oxford University Hospitals, Oxford, United Kingdom; Myriam Labopin and Mohamad Mohty, Hôpital Saint-Antoine, Paris University; Gerard Socie, Hôpital St Louis, Paris; Mauricette Michallet, Hôpital Edouard Herriot, Lyon; Ibrahim Yakoub-Agha, University Hospital Lille, France; Ali Unal, Erciyes Medical School, Kayseri, Turkey; Tarek Ben Othman, Centre National de Greffe de Moelle, Tunis, Tunisia; Antonio Campos, Instituto Portugues de Oncologia do Porto, Porto, Portugal; Liisa Volin, Helsinki University Central Hospital, Helsinki, Finland; Xavier Poire, Cliniques Universitaires St Luc, Brussels, Belgium; Mahmoud Aljurf, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Henrik Sengelov, National University Hospital, Copenhagen, Denmark; Jakob Passweg, University Hospital, Basel, Switzerland; and Hendrik Veelken, Leiden University Medical Center, Leiden, the Netherlands.
Abstract
PURPOSE: Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with busulfan (Bu) are currently the most common myeloablative regimens used in allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous leukemia (AML). Intravenous (IV) Bu has more predictable bioavailability and a safer toxicity profile than the oral formulation. Comparative studies of outcomes have been performed between oral Bu/Cy and Cy/TBI, but there have been no comparative trials in the era of IV Bu. PATIENTS AND METHODS: We performed a retrospective registry-based study comparing outcomes of patients with AML in first or second remission after alloSCT from sibling donors who underwent IV Bu/Cy (n = 795) or Cy/TBI (n = 864) conditioning. RESULTS: Engraftment rate was 98% and 99% after IV Bu/Cy and Cy/TBI, respectively. Grade 2 to 4 acute graft-versus-host disease (GVHD) was significantly lower in the IV Bu/Cy compared with Cy/TBI group (P < .001). Similarly, chronic GVHD was significantly lower in the IV Bu/Cy compared with Cy/TBI group (P = .003). Cumulative incidence of 2-year nonrelapse mortality (NRM; ± standard deviation [SD]) was 12% ± 1% in the IV Bu/Cy group and 15% ± 2% in the Cy/TBI group (P = .14), and 2-year relapse incidence (RI; ± SD) was 26% ± 3% and 21% ± 1%, respectively (P = .012). Leukemia-free survival (LFS) rate (± SD) was 61% ± 2% after IV Bu/Cy and 64% ± 2% after Cy/TBI (P = .27). In multivariable analysis, adjusting for differences between both groups, patients who received IV Bu/Cy had lower acute and chronic GVHD, higher RI, and a trend toward lower NRM. LFS was not statistically different between the two conditioning regimens. CONCLUSION: This retrospective study shows that final outcomes after myeloablative conditioning using IV Bu/Cy were not statistically different from those after Cy/TBI.
PURPOSE:Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with busulfan (Bu) are currently the most common myeloablative regimens used in allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous leukemia (AML). Intravenous (IV) Bu has more predictable bioavailability and a safer toxicity profile than the oral formulation. Comparative studies of outcomes have been performed between oral Bu/Cy and Cy/TBI, but there have been no comparative trials in the era of IV Bu. PATIENTS AND METHODS: We performed a retrospective registry-based study comparing outcomes of patients with AML in first or second remission after alloSCT from sibling donors who underwent IV Bu/Cy (n = 795) or Cy/TBI (n = 864) conditioning. RESULTS: Engraftment rate was 98% and 99% after IV Bu/Cy and Cy/TBI, respectively. Grade 2 to 4 acute graft-versus-host disease (GVHD) was significantly lower in the IV Bu/Cy compared with Cy/TBI group (P < .001). Similarly, chronic GVHD was significantly lower in the IV Bu/Cy compared with Cy/TBI group (P = .003). Cumulative incidence of 2-year nonrelapse mortality (NRM; ± standard deviation [SD]) was 12% ± 1% in the IV Bu/Cy group and 15% ± 2% in the Cy/TBI group (P = .14), and 2-year relapse incidence (RI; ± SD) was 26% ± 3% and 21% ± 1%, respectively (P = .012). Leukemia-free survival (LFS) rate (± SD) was 61% ± 2% after IV Bu/Cy and 64% ± 2% after Cy/TBI (P = .27). In multivariable analysis, adjusting for differences between both groups, patients who received IV Bu/Cy had lower acute and chronic GVHD, higher RI, and a trend toward lower NRM. LFS was not statistically different between the two conditioning regimens. CONCLUSION: This retrospective study shows that final outcomes after myeloablative conditioning using IV Bu/Cy were not statistically different from those after Cy/TBI.
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