title: Allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies after dose-escalated treosulfan/fludarabine conditioning.
abstract: OBJECTIVE
  Treosulfan was introduced recently as a conditioning agent for allogeneic blood stem-cell transplantation. The favorable nonhematologic toxicity profile at 3 x 10 g/m(2) was the basis for dose escalation in this prospective, multicenter trial.
  
  
  METHODS
  Fifty-six patients with various hematologic malignancies who were not eligible for standard conditioning were treated with one of three doses: 10 g/m(2), 12 g/m(2), or 14 g/m(2) of intravenous treosulfan, which was administered on days -6 to -4 combined with fludarabine 30 mg/m(2) on days -6 to -2. Patients in complete remission (CR; 42%) or non-CR (58%) received grafts from matched related (47%) or matched unrelated (51%) donors; one patient had a mismatched related donor (2%).
  
  
  RESULTS
  No engraftment failure occurred. Overall, extramedullary toxicity and the nonrelapse mortality rate at 2 years (20%) were low and did not increase with dose. Cumulative incidence of relapse/progression reached 31%. The overall survival and progression-free survival rates were 64% and 49%, respectively, in the total study population. An inverse dose dependency of relapse incidence was indicated in the subgroup receiving transplantations from matched related donors (P = .0568).
  
  
  CONCLUSIONS
  Treosulfan-based conditioning was feasible at all three doses. The 3 x 14 g/m(2) dose was selected for additional studies, because it combines desired characteristics of low toxicity and a low relapse rate.
authors.affiliation: University of Rostock, Rostock, Germany. casper.jochen@klinikum-oldenburg.de
authors.forename: Jochen
authors.initials: J
authors.lastname: Casper
authors.forename: Daniel
authors.initials: D
authors.lastname: Wolff
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Knauf
authors.forename: Igor W
authors.initials: IW
authors.lastname: Blau
authors.forename: Tapani
authors.initials: T
authors.lastname: Ruutu
authors.forename: Liisa
authors.initials: L
authors.lastname: Volin
authors.forename: Hannes
authors.initials: H
authors.lastname: Wandt
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schäfer-Eckart
authors.forename: Jerzy
authors.initials: J
authors.lastname: Holowiecki
authors.forename: Sebastian
authors.initials: S
authors.lastname: Giebel
authors.forename: Johan
authors.initials: J
authors.lastname: Aschan
authors.forename: Axel R
authors.initials: AR
authors.lastname: Zander
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.forename: Inken
authors.initials: I
authors.lastname: Hilgendorf
authors.forename: Joachim
authors.initials: J
authors.lastname: Baumgart
authors.forename: Heidrun A
authors.initials: HA
authors.lastname: Mylius
authors.forename: Uwe
authors.initials: U
authors.lastname: Pichlmeier
authors.forename: Mathias
authors.initials: M
authors.lastname: Freund
mesh_terms: D000293:Adolescent; D000328:Adult; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine