title: Results from a clofarabine-busulfan-containing, reduced-toxicity conditioning regimen prior to allogeneic stem cell transplantation: the phase 2 prospective CLORIC trial.
abstract: We prospectively evaluated the safety and efficacy of a clofarabine, intravenous busulfan and antithymocyte globulin-based reduced-toxicity conditioning (CloB2A2) regimen before allogeneic stem cell transplantation. Thirty high-risk patients (median age: 59 years; acute myeloid leukemia n=11, acute lymphoblastic leukemia n=13; myelodysplastic syndrome n=5, bi-phenotypic leukemia n=1) were included in this phase 2 study. At time of their transplant, 20 and seven patients were in first and second complete remission, respectively, while three patients with myelodysplastic syndrome were responding to chemotherapy or who had not been previously treated. The CloB2A2 regimen consisted of clofarabine 30 mg/m(2)/day for 4 days, busulfan 3.2 mg/kg/day for 2 days and antithymocyte globulin 2.5 mg/kg/day for 2 days. The median follow-up was 23 months. Engraftment occurred in all patients. The 1-year overall survival, leukemia-free survival, relapse incidence and non-relapse mortality rates were 63±9%, 57±9%, 40±9%, and 3.3±3%, respectively. Comparing patients with acute myeloid leukemia/myelodysplastic syndrome versus those with acute lymphoblastic leukemia/bi-phenotypic leukemia, the 1-year overall and leukemia-free survival rates were 75±10% versus 50±13%, respectively (P=0.07) and 69±12% versus 43±13%, respectively (P=0.08), while the 1-year relapse incidence was 25±11% versus 57±14%, respectively (P=0.05). The CloB2A2 regimen prior to allogeneic stem cell transplantation is feasible, allowing for full engraftment and low toxicity. Disease control appears to be satisfactory, especially in patients with acute myeloid leukemia/myelodysplastic syndrome. The trial was registered at www.clinicaltrials.gov no. NCT00863148.
authors.affiliation: Hematology Department, CHU Hotel-Dieu, Nantes patrice.chevallier@chu-nantes.fr.
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
authors.affiliation: Université Pierre & Marie Curie, Paris INSERM, UMRs 938, Paris Hôpital Saint-Antoine, AP-HP, Paris.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: Hematology Department, Hopital Saint-Louis, Paris.
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.affiliation: Hematology Department, CHU, Bordeaux.
authors.forename: Reza
authors.initials: R
authors.lastname: Tabrizi
authors.affiliation: Hematology Department, Institut Paoli-Calmette, Marseille.
authors.forename: Sabine
authors.initials: S
authors.lastname: Furst
authors.affiliation: Hematology Department, CHU, Strasbourg, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lioure
authors.affiliation: Hematology Department, CHU Hotel-Dieu, Nantes.
authors.forename: Thierry
authors.initials: T
authors.lastname: Guillaume
authors.affiliation: Hematology Department, CHU Hotel-Dieu, Nantes.
authors.forename: Jacques
authors.initials: J
authors.lastname: Delaunay
authors.affiliation: Hematology Department, Hopital Saint-Louis, Paris.
authors.forename: Régis Peffault
authors.initials: RP
authors.lastname: de La Tour
authors.affiliation: Hematology Department, CHU, Bordeaux.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Vigouroux
authors.affiliation: Hematology Department, Institut Paoli-Calmette, Marseille.
authors.forename: Jean
authors.initials: J
authors.lastname: El-Cheikh
authors.affiliation: Hematology Department, Institut Paoli-Calmette, Marseille.
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
authors.affiliation: Hematology Department, CHU, Lyon.
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.affiliation: Hematology Department, CHU, Strasbourg, France.
authors.forename: Karin
authors.initials: K
authors.lastname: Bilger
authors.affiliation: Hematology Department, CHU, Bordeaux.
authors.forename: Noel
authors.initials: N
authors.lastname: Milpied
authors.affiliation: Hematology Department, CHU Hotel-Dieu, Nantes.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Hematology Department, CHU Hotel-Dieu, Nantes Université Pierre & Marie Curie, Paris INSERM, UMRs 938, Paris Hôpital Saint-Antoine, AP-HP, Paris.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
mesh_terms: D000227:Adenine Nucleotides / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001087:Arabinonucleosides / Q000627:therapeutic use; D002066:Busulfan / Q000627:therapeutic use; D000077866:Clofarabine; D004334:Drug Administration Schedule; D005260:Female; D006085:Graft Survival / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015456:Leukemia, Biphenotypic, Acute / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012008:Recurrence; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D000227:Adenine Nucleotides; D000961:Antilymphocyte Serum; D001087:Arabinonucleosides; D019653:Myeloablative Agonists; D000077866:Clofarabine; D002066:Busulfan