title: Reduced-toxicity conditioning with fludarabine, once-daily intravenous busulfan, and antithymocyte globulins prior to allogeneic stem cell transplantation: results of a multicenter prospective phase 2 trial.
abstract: BACKGROUND
  The optimal intensity of myeloablation delivered as part of a reduced-intensity/toxicity conditioning (RIC/RTC) regimen to decrease the recurrence rate, without increasing nonrecurrence mortality (NRM), remains to be established.
  
  
  METHODS
  The current phase 2, prospective, multicenter trial aimed to assess the efficacy and safety of an RIC/RTC regimen based on busulfan at a dose of 130 mg/m(2) /day intravenously for 3 days, fludarabine at a dose of 30 mg/m(2) /day for 5 days, and antithymocyte globulins at a dose of 2.5 mg/kg/day for 2 days. A total of 80 patients (median age, 53 years; range, 25-64 years) with hematological malignancies were included.
  
  
  RESULTS
  With a median follow-up of 21 months (range, 12-36.5 months), the Kaplan-Meier estimates of overall and disease-free survival at 2 years were 62% (95% confidence interval [95% CI], 51%-73%) and 50% (95% CI, 33%-57%), respectively. The cumulative incidences of grade 2 to 4 acute graft-versus-host disease (GVHD) and chronic GVHD (all grades) were 29% (95% CI, 19%-39%) and 35% (95% CI, 24%-46%), respectively. At 2 years, the cumulative incidence of recurrence/disease progression and NRM were 44% (95% CI, 31%-56%) and 11% (95% CI, 6%-19%), respectively. Patient age, diagnosis, donor type, sex, presence of comorbidities, and the Hematopoietic cell transplantation-specific comorbidities index did not appear to have any statistically significant impact on NRM, recurrence/disease progression, disease-free survival, or overall survival.
  
  
  CONCLUSIONS
  The RIC/RTC regimen used in the current study appeared to be safe, with a low NRM rate at 2 years noted among high-risk patients, and efficient disease control, warranting prospective phase 3 trials.
authors.affiliation: Hematology Department, Nantes University Medical Center, Nantes, France; Cancerologie Reserch Center Nantes Angers, INSERM 892, CNRS 6299, University of Nantes School of Medicine, Nantes, France; Center for Clinical Investigation of Cancer, Nantes University Medical Center, Nantes, France; Hematology Department, AP-HP, Paris University 6, Saint Antoine Hospital, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.forename: Florent
authors.initials: F
authors.lastname: Malard
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
authors.forename: Noel
authors.initials: N
authors.lastname: Milpied
authors.forename: Sabine
authors.initials: S
authors.lastname: Furst
authors.forename: Resa
authors.initials: R
authors.lastname: Tabrizi
authors.forename: Thierry
authors.initials: T
authors.lastname: Guillaume
authors.forename: Stéphane
authors.initials: S
authors.lastname: Vigouroux
authors.forename: Jean
authors.initials: J
authors.lastname: El-Cheikh
authors.forename: Jacques
authors.initials: J
authors.lastname: Delaunay
authors.forename: Steven
authors.initials: S
authors.lastname: Le Gouill
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage* / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
keywords: allogeneic stem cell transplantation; intravenous busulfan; prospective trial; reduced-intensity conditioning; submyeloablative conditioning