title: Reduced-toxicity conditioning with treosulfan and fludarabine in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndromes: final results of an international prospective phase II trial.
abstract: BACKGROUND
  An alternative reduced-toxicity conditioning regimen for allogeneic transplantation, based on treosulfan and fludarabine, has recently been identified. The rationale for this study was to investigate the efficacy and safety of this regimen prospectively in patients with a primary myelodysplastic syndrome.
  
  
  METHODS
  A total of 45 patients with primary myelodysplastic syndromes were conditioned with 3×14 g/m(2) treosulfan and 5×30 mg/m(2) fludarabine followed by allogeneic hematopoietic stem cell transplantation. Subtypes of myelodysplastic syndromes were refractory anemia with excess blasts-2 (44%), refractory cytopenia with multilineage dysplasia (27%), refractory anemia (9%), refractory anemia with ringed sideroblasts (4%), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (4%), refractory anemia with excess blasts-1 (2%), and myelodysplastic syndrome with isolated del (5q) (2%). The myelodysplastic syndrome was unclassified in 7% of the patients. Forty-seven percent of the patients had a favorable karyotype, 29% an unfavorable one, and 18% an intermediate karyotype. Patients were evaluated for engraftment, adverse events, graft-versus-host disease, non-relapse mortality, relapse incidence, overall survival and disease-free survival.
  
  
  RESULTS
  All but one patient showed primary engraftment of neutrophils after a median of 17 days. Non-hematologic adverse events of grade III-IV in severity included mainly infections and gastrointestinal symptoms (80% and 22% of the patients, respectively). Acute graft-versus-host disease grade II-IV developed in 24%, and extensive chronic graft-versus-host disease in 28% of the patients. After a median follow-up of 780 days, the 2-year overall and disease-free survival estimates were 71% and 67%, respectively. The 2-year cumulative incidences of non-relapse mortality and relapse were 17% and 16%, respectively.
  
  
  CONCLUSIONS
  Our safety and efficacy data suggest that treosulfan-based conditioning therapy is a promising treatment option for patients with myelodysplastic syndromes. clinicaltrials.gov identifier: NCT01062490.
authors.affiliation: Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland. tapani.ruutu@hus.fi
authors.forename: Tapani
authors.initials: T
authors.lastname: Ruutu
authors.forename: Liisa
authors.initials: L
authors.lastname: Volin
authors.forename: Dietrich W
authors.initials: DW
authors.lastname: Beelen
authors.forename: Rudolf
authors.initials: R
authors.lastname: Trenschel
authors.forename: Juergen
authors.initials: J
authors.lastname: Finke
authors.forename: Marc
authors.initials: M
authors.lastname: Schnitzler
authors.forename: Jerzy
authors.initials: J
authors.lastname: Holowiecki
authors.forename: Sebastian
authors.initials: S
authors.lastname: Giebel
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Markiewicz
authors.forename: Lutz
authors.initials: L
authors.lastname: Uharek
authors.forename: Igor W
authors.initials: IW
authors.lastname: Blau
authors.forename: Joachim
authors.initials: J
authors.lastname: Kienast
authors.forename: Matthias
authors.initials: M
authors.lastname: Stelljes
authors.forename: Kajsa
authors.initials: K
authors.lastname: Larsson
authors.forename: Axel R
authors.initials: AR
authors.lastname: Zander
authors.forename: Martin
authors.initials: M
authors.lastname: Gramatzki
authors.forename: Roland
authors.initials: R
authors.lastname: Repp
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.forename: Gernot
authors.initials: G
authors.lastname: Stuhler
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
authors.forename: Jochen
authors.initials: J
authors.lastname: Casper
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002066:Busulfan / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D046528:Chimerism; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy*; D012008:Recurrence; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine