title: Treosulfan and fludarabine: a new toxicity-reduced conditioning regimen for allogeneic hematopoietic stem cell transplantation.
abstract: New conditioning regimens are being explored to reduce toxicity and enable allogeneic bone marrow transplantation in patients not eligible for conventional transplantation. We have investigated treosulfan, an alkylating agent, with the aim of developing an efficient and reliable but less-toxic conditioning regimen. A series of 30 patients who were not eligible for standard conditioning therapy received transplants from HLA-matched related (n = 14) or unrelated (n = 16) donors after administration of treosulfan 10 g/m2 intravenously daily for 3 days and fludarabine 30 mg/m2 intravenously daily for 5 days. Patients receiving grafts from unrelated donors also were given rabbit antithymocyte globulin 10 mg/kg intravenously daily for 3 days. All patients achieved prompt neutrophil and platelet recovery. Extramedullary toxicity was generally mild with Common Toxicity Criteria (CTC) grade 3 or 4 attributable to the conditioning seen only with transaminases. Complete donor chimerism was achieved by 90% of the patients. Acute graft-versus-host disease (GVHD) grade III or IV developed in 14% of the patients and chronic GVHD in 39%. An estimated overall survival rate of 73% and an event-free survival rate of 49% have been reached after a median of 22 months (range, 7.4-33.4 months). In summary, the combination of treosulfan and fludarabine is a safe and efficient conditioning regimen.
authors.affiliation: Department of Hematology and Oncology, University of Rostock, PO Box 100888, 18055 Rostock, Germany. jochen.casper@med.uni-rostock.de
authors.forename: Jochen
authors.initials: J
authors.lastname: Casper
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Knauf
authors.forename: Thomas
authors.initials: T
authors.lastname: Kiefer
authors.forename: Daniel
authors.initials: D
authors.lastname: Wolff
authors.forename: Beate
authors.initials: B
authors.lastname: Steiner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hammer
authors.forename: Rudolf
authors.initials: R
authors.lastname: Wegener
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Kleine
authors.forename: Stefan
authors.initials: S
authors.lastname: Wilhelm
authors.forename: Agnes
authors.initials: A
authors.lastname: Knopp
authors.forename: Gernot
authors.initials: G
authors.lastname: Hartung
authors.forename: Gottfried
authors.initials: G
authors.lastname: Dölken
authors.forename: Mathias
authors.initials: M
authors.lastname: Freund
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000477:Alkylating Agents / Q000627:therapeutic use; D002066:Busulfan / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D002908:Chronic Disease; D005190:Family; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use* / Q000633:toxicity; D007938:Leukemia / Q000145:classification / Q000628:therapy*; D019520:Living Donors / Q000706:statistics & numerical data; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy; D033581:Stem Cell Transplantation; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000276:immunology*; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D000477:Alkylating Agents; D007166:Immunosuppressive Agents; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine