title: Treosulfan and fludarabine low-toxicity conditioning for allogeneic haematopoietic stem cell transplantation in chronic myeloid leukaemia.
abstract: Allogeneic haematopoietic stem cell transplantation (alloHSCT) is the only treatment of proven long-term efficacy in chronic myeloid leukaemia (CML), although high non-relapse mortality (NRM) observed after conventional myeloablative conditioning limits its applicability. This phase II trial evaluated the efficacy and toxicity of a new preparative regimen consisting of treosulfan 3 x 14 g/m(2) and fludarabine 5 x 30 mg/m(2), in patients with CML in chronic phase. Among the 40 patients included, 18 received alloHSCT from a sibling and 22 from an unrelated donor. All patients engrafted with 92.5% of cases achieving complete donor chimaerism by day +100. All but one patient had achieved complete cytogenetic remission on day +100. Grade III or IV non-haematological toxicities included: neutropenic fever (10%), nausea/vomiting (10%), elevated liver enzymes (5%) and infection (2.5%). The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 22.5% and extensive chronic GVHD, 14%. The 2-year probability of overall survival, leukaemia-free survival and NRM was 85%, 82.5% and 15% respectively. At 1 year post-transplant, 85% of survivors had a Karnofsky index of 100%. We concluded that treosulfan and fludarabine conditioning is a low-toxicity regimen with high anti-leukaemic potential that seems feasible in CML patients referred for alloHSCT.
authors.affiliation: Department of Haematology and BMT, Silesian Medical University, Katowice, Poland. holow@sum.edu.pl
authors.forename: Jerzy
authors.initials: J
authors.lastname: Holowiecki
authors.forename: Sebastian
authors.initials: S
authors.lastname: Giebel
authors.forename: Jerzy
authors.initials: J
authors.lastname: Wojnar
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Krawczyk-Kulis
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Markiewicz
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Holowiecka-Goral
authors.forename: Mathias
authors.initials: M
authors.lastname: Freund
authors.forename: Jochen
authors.initials: J
authors.lastname: Casper
mesh_terms: D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine