title: Intravenous busulfan for autologous stem cell transplantation in adult patients with acute myeloid leukemia: a survey of 952 patients on behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.
abstract: Oral busulfan is the historical backbone of the busulfan+cyclophosphamide regimen for autologous stem cell transplantation. However intravenous busulfan has more predictable pharmacokinetics and less toxicity than oral busulfan; we, therefore, retrospectively analyzed data from 952 patients with acute myeloid leukemia who received intravenous busulfan for autologous stem cell transplantation. Most patients were male (n=531, 56%), and the median age at transplantation was 50.5 years. Two-year overall survival, leukemia-free survival, and relapse incidence were 67±2%, 53±2%, and 40±2%, respectively. The non-relapse mortality rate at 2 years was 7±1%. Five patients died from veno-occlusive disease. Overall leukemia-free survival and relapse incidence at 2 years did not differ significantly between the 815 patients transplanted in first complete remission (52±2% and 40±2%, respectively) and the 137 patients transplanted in second complete remission (58±5% and 35±5%, respectively). Cytogenetic risk classification and age were significant prognostic factors: the 2-year leukemia-free survival was 63±4% in patients with good risk cytogenetics, 52±3% in those with intermediate risk cytogenetics, and 37 ± 10% in those with poor risk cytogenetics (P=0.01); patients ≤50 years old had better overall survival (77±2% versus 56±3%; P<0.001), leukemia-free survival (61±3% versus 45±3%; P<0.001), relapse incidence (35±2% versus 45±3%; P<0.005), and non-relapse mortality (4±1% versus 10±2%; P<0.001) than older patients. The combination of intravenous busulfan and high-dose melphalan was associated with the best overall survival (75±4%). Our results suggest that the use of intravenous busulfan simplifies the autograft procedure and confirm the usefulness of autologous stem cell transplantation in acute myeloid leukemia. As in allogeneic transplantation, veno-occlusive disease is an uncommon complication after an autograft using intravenous busulfan.
authors.affiliation: Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.affiliation: Acute Leukemia Working Party -EBMT, Hôpital Saint Antoine, AP-HP, Université Pierre et Marie Curie Paris 6 UPMC, INSERM UMR-S 938, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: Acute Leukemia Working Party -EBMT, Hôpital Saint Antoine, AP-HP, Université Pierre et Marie Curie Paris 6 UPMC, INSERM UMR-S 938, Paris, France Department of Hematology and Cell Therapy, Hospital Saint Antoine, Paris, France norbert-claude.gorin@sat.aphp.fr.
authors.forename: Norbert-Claude
authors.initials: NC
authors.lastname: Gorin
authors.affiliation: Cardarelli Hospital, Napoli, Italy.
authors.forename: Felicetto
authors.initials: F
authors.lastname: Ferrara
authors.affiliation: Hospital Universitario La Fe, University of Valencia, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
authors.affiliation: First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Depei
authors.initials: D
authors.lastname: Wu
authors.affiliation: Hospital Reina Sofia, Córdoba, Spain.
authors.forename: Antonio Torres
authors.initials: AT
authors.lastname: Gomez
authors.affiliation: Department of Hematology and Cell Therapy, Hospital Saint Antoine, Paris, France.
authors.forename: Simona
authors.initials: S
authors.lastname: Lapusan
authors.affiliation: Azienda Ospedaliera, Reggio Calabria, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Irrera
authors.affiliation: Hospital Sao Joao and School of Medicine, Porto, Portugal.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Guimaraes
authors.affiliation: Hospital dos Capuchos, Lisboa, Portugal.
authors.forename: Aida Botelho
authors.initials: AB
authors.lastname: Sousa
authors.affiliation: Hospital San Martino, Genova, Italy.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Carella
authors.affiliation: Centre Paoli Calmettes, Marseille, France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.affiliation: Rome Transplant Network, Rome, Italy.
authors.forename: William
authors.initials: W
authors.lastname: Arcese
authors.affiliation: Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Avichai
authors.initials: A
authors.lastname: Shimoni
authors.affiliation: Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Raanan
authors.initials: R
authors.lastname: Berger
authors.affiliation: Churchill Hospital, Oxford University, UK.
authors.forename: Vanderson
authors.initials: V
authors.lastname: Rocha
authors.affiliation: Acute Leukemia Working Party -EBMT, Hôpital Saint Antoine, AP-HP, Université Pierre et Marie Curie Paris 6 UPMC, INSERM UMR-S 938, Paris, France Department of Hematology and Cell Therapy, Hospital Saint Antoine, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation / Q000401:mortality; D002066:Busulfan / Q000008:administration & dosage*; D003625:Data Collection / Q000379:methods; D005060:Europe / Q000453:epidemiology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006801:Humans; D007262:Infusions, Intravenous; D015470:Leukemia, Myeloid, Acute / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D014182:Transplantation, Autologous / Q000401:mortality; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002066:Busulfan