title: Conditioning with fludarabine and targeted busulfan for transplantation of allogeneic hematopoietic stem cells.
abstract: A regimen of busulfan and cyclophosphamide is standard therapy before transplantation of allogeneic hematopoietic stem cells in patients with chronic myelogenous leukemia (CML) or myelodysplastic syndrome (MDS). The clinical trial reported here was undertaken to test the hypothesis that fludarabine can replace cyclophosphamide in this regimen and facilitate donor engraftment with reduced toxicity. The conditioning regimen consisted of 30 mg/m2 intravenous fludarabine daily from day -9 to day -6, and oral busulfan given at 1 mg/kg 4 times a day every 6 hours from day -5 to day -2, with doses adjusted to target plasma levels of 900 +/- 100 ng/mL at steady state. Cyclosporine and methotrexate were used for prophylaxis for graft-versus-host disease. Enrolled were 42 patients with high-risk CML (n = 4) or MDS (n = 38). The median patient age was 52 years (range, 12-65 years). Mobilized blood stem cells were obtained from HLA-compatible siblings (n = 16) or unrelated donors (n = 26). Engraftment was achieved in all patients, and the day-100 regimen-related mortality was 7%. With a median follow-up of 18 months (range, 13-27 months), the probabilities of overall survival, disease-free survival, and nonrelapse mortality were 42.4%, 34.9%, and 24%, respectively. These data indicate that the combination of fludarabine and targeted busulfan is sufficiently immunosuppressive to facilitate engraftment of blood stem cells from HLA-matched siblings and unrelated donors. Based on these encouraging results, further studies of fludarabine and targeted busulfan are warranted in standard-risk patients.
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany. bornhaeuser@mk1.med.tu-dresden.de
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhauser
authors.forename: Barry
authors.initials: B
authors.lastname: Storer
authors.forename: John T
authors.initials: JT
authors.lastname: Slattery
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: H Joachim
authors.initials: HJ
authors.lastname: Deeg
authors.forename: John
authors.initials: J
authors.lastname: Hansen
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.forename: George B
authors.initials: GB
authors.lastname: McDonald
authors.forename: W Garrett
authors.initials: WG
authors.lastname: Nichols
authors.forename: Jerald
authors.initials: J
authors.lastname: Radich
authors.forename: Ann
authors.initials: A
authors.lastname: Woolfrey
authors.forename: Andreas
authors.initials: A
authors.lastname: Jenke
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schleyer
authors.forename: Christian
authors.initials: C
authors.lastname: Thiede
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D002066:Busulfan / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D012008:Recurrence; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000276:immunology; D014740:Vidarabine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine