title: Dose-escalated treosulphan in combination with cyclophosphamide as a new preparative regimen for allogeneic haematopoietic stem cell transplantation in patients with an increased risk for regimen-related complications.
abstract: Treosulphan has recently demonstrated antileukaemic activity and potent haematopoietic stem cell toxicity. Dose-escalated treosulphan (3 x 12 or 3 x 14 g/m2) combined with cyclophosphamide (Cy) was chosen for a new preparative regimen before allogeneic haematopoietic stem cell transplantation in 18 patients (median age 44, range 19-64 years) with haematological malignancies, considered ineligible for other myeloablative preparative regimens. Pharmacokinetic studies demonstrated rapid treosulphan plasma clearance and a dose-dependent increase of its maximum plasma concentrations and area under the concentration-time curves. Rapid and sustained white blood cell and platelet recovery and full donor chimerism was attained in all evaluable patients. Nonhaematological regimen-related CTC grades 3-4 adverse events were transient and predominantly consisted of cardiac (28%), gastrointestinal (39%), and hepatic (39%) toxicities. The 1-year nonrelapse mortality was 22%. Principal causes of transplant-related lethal events were infections in three of four affected patients. Only one patient died from regimen-related cardiac toxicity. The 1-year relapse estimate is 22%, overall and progression-free survival estimates are 67 and 56%, respectively. In conclusion, this new treosulphan and Cy combination is an effective, comparatively well-tolerated myeloablative preparative regimen even in patients with an increased risk for regimen-related toxic complications.
authors.affiliation: Department of Bone Marrow Transplantation, University Hospital Essen, Germany. dietrich.beelen@uni-essen.de
authors.forename: D W
authors.initials: DW
authors.lastname: Beelen
authors.forename: R
authors.initials: R
authors.lastname: Trenschel
authors.forename: J
authors.initials: J
authors.lastname: Casper
authors.forename: M
authors.initials: M
authors.lastname: Freund
authors.forename: R A
authors.initials: RA
authors.lastname: Hilger
authors.forename: M E
authors.initials: ME
authors.lastname: Scheulen
authors.forename: N
authors.initials: N
authors.lastname: Basara
authors.forename: A A
authors.initials: AA
authors.lastname: Fauser
authors.forename: B
authors.initials: B
authors.lastname: Hertenstein
authors.forename: H A
authors.initials: HA
authors.lastname: Mylius
authors.forename: J
authors.initials: J
authors.lastname: Baumgart
authors.forename: U
authors.initials: U
authors.lastname: Pichlmeier
authors.forename: J R
authors.initials: JR
authors.lastname: Hahn
authors.forename: E
authors.initials: E
authors.lastname: Holler
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity; D002066:Busulfan / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D002423:Cause of Death; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D010599:Pharmacokinetics; D012008:Recurrence; D018570:Risk Assessment; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; C018404:treosulfan; D002066:Busulfan