title: Treosulfan/fludarabine: a new conditioning regimen in allogeneic transplantation.
abstract: Recently, the water-soluble bifunctional alkylating agent treosulfan demonstrated broad stem cell toxicity, immunosuppressive as well as antileukemic activity. Due to its well known low non-hematologic toxicity profile, treosulfan was considered an alternative agent for conditioning prior to allogeneic transplantation. A first clinical study, combining 3 x 10 g/m2 of treosulfan with 5 x 30 mg/m2 of fludarabine, demonstrated the feasibility of this conditioning. A fast, reliable and complete development of the donor hematopoiesis was evident as well as a low non-hematologic toxicity, transplantation-related mortality and relapse rate. In a second study treosulfan was escalated from 3 x 10 to 3 x 12 and 3 x 14 g/m2. In this protocol, 55 pts (patients) not amenable to standard conditioning suffering from various hematological malignancies were included. Complete donor chimerism was reached by day 28 in 80% of the pts. So far, 8 pts (11%) died without disease progression and 11 pts (20%) relapsed. Treosulfan was very well tolerated. Especially no hepatic VOD, severe cardiac or pulmonary toxicity was noted. Acute GvHD (degrees 11-IV) occurred in 44% and chronic GvHD in 45% of pts. Considering the poor prognosis of these study populations, treosulfan-based conditioning is considered to be safe and efficient. New phase 11 clinical protocols in AML and MDS will be initiated.
authors.affiliation: University of Rostock, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Casper
authors.forename: W
authors.initials: W
authors.lastname: Knauf
authors.forename: I
authors.initials: I
authors.lastname: Blau
authors.forename: T
authors.initials: T
authors.lastname: Ruutu
authors.forename: L
authors.initials: L
authors.lastname: Volin
authors.forename: H
authors.initials: H
authors.lastname: Wandt
authors.forename: K
authors.initials: K
authors.lastname: Schafer-Eckart
authors.forename: J
authors.initials: J
authors.lastname: Holowiecki
authors.forename: S
authors.initials: S
authors.lastname: Giebel
authors.forename: J
authors.initials: J
authors.lastname: Aschan
authors.forename: A
authors.initials: A
authors.lastname: Zander
authors.forename: N
authors.initials: N
authors.lastname: Kroger
authors.forename: G
authors.initials: G
authors.lastname: Doelken
authors.forename: M
authors.initials: M
authors.lastname: Freund
mesh_terms: D002066:Busulfan / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D007938:Leukemia / Q000145:classification / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D017708:Leukocyte Transfusion; D008223:Lymphoma / Q000145:classification / Q000628:therapy*; D009190:Myelodysplastic Syndromes / Q000188:drug therapy; D033581:Stem Cell Transplantation; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000276:immunology* / Q000379:methods*; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine