title: Higher busulfan dose intensity appears to improve leukemia-free and overall survival in AML allografted in CR2: An analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.
abstract: Allogeneic hematopoietic cell transplantation is a potentially curative treatment in patients with acute myeloid leukemia. Recent advances in the field of hematopoietic cell allografting have resulted in a practice shift, favoring less intense preparative regimens. We present results of a retrospective comparative analysis of two preparative regimens, namely FB2 (IV fludarabine plus IV busulfan 6.4mg/kg±10%) and FB4 (IV fludarabine plus IV busulfan 12.8mg/kg ±10%), in patients with acute myeloid leukemia undergoing hematopoietic cell allografting in second complete remission at EBMT participating centers. Between 2003 and 2010, 128 AML patients in second complete remission were allografted following a preparative regimen of FB2 (n=88) or FB4 (n=40). The median time-to-neutrophil engraftment was similar whether patients received FB2 (16 (5-38) days) or FB4 (16 (9-29) days), p=0.45. A multivariate analysis showed that use of FB4 resulted in improved 2-year leukemia-free (HR=0.44 (95%CI=0.21, 0.94), p=0.03) and overall survival (HR=0.38 (95%CI=0.16, 0.86), p=0.02). Cumulative incidence of non-relapse mortality (2-year) for all patients was 21% (95%CI=14-28%). Our analysis suggests that FB4 improves 2-year leukemia-free and overall survival in AML allografted in second complete remission. A confirmatory randomized controlled trial that compares these two preparative regimens (FB2 vs. FB4) in AML in CR2 is definitely warranted.
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL, United States.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Kharfan-Dabaja
authors.affiliation: Acute Leukemia Working Party of EBMT, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: Division of Hematology-Oncology and BMT Program, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Ali
authors.initials: A
authors.lastname: Bazarbachi
authors.affiliation: Service d'Hématologie Greffe, Hôpital Saint Louis, Paris, France.
authors.forename: Gerard
authors.initials: G
authors.lastname: Socie
authors.affiliation: Bone Marrow Transplantation Centre, Univ. Hospital Eppendorf, Hamburg, Germany.
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kroeger
authors.affiliation: Unité de Transplantation et de Thérapie Cellulaire (U2T), Institut Paoli-Calmettes, Marseille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Veelken
authors.affiliation: Dept of Hematology, Hospital Universitario Marqués de Valdecilla, Instituto de Formación e Investigación Marqués de Valdecilla, Santander, Spain.
authors.forename: Arancha
authors.initials: A
authors.lastname: Bermudez
authors.affiliation: Dept of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Reuven
authors.initials: R
authors.lastname: Or
authors.affiliation: CHU Hautepierre-Département d'Hématologie et Oncologie, Strasbourg, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lioure
authors.affiliation: University Hospital, Department of Bone Marrow Transplantation, Essen, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Beelen
authors.affiliation: Service d'Hématologie, CHU, Montpellier, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Fegueux
authors.affiliation: Centre Pierre et Marie Curie, Alger, Algeria.
authors.forename: Rose Marie
authors.initials: RM
authors.lastname: Hamladji
authors.affiliation: Acute Leukemia Working Party of EBMT, Paris, France; Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.affiliation: Acute Leukemia Working Party of EBMT, Paris, France; Département d'Hématologie, Hopital Saint Antoine, Paris, France. Electronic address: mohamad.mohty@inserm.fr.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D002066:Busulfan / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
keywords: Acute myeloid leukemia; Allogeneic hematopoietic cell transplantation; Leukemia-free survival; Overall survival; Second complete remission