title: Busulfan 12 mg/kg plus melphalan 140 mg/m2 versus melphalan 200 mg/m2 as conditioning regimens for autologous transplantation in newly diagnosed multiple myeloma patients included in the PETHEMA/GEM2000 study.
abstract: BACKGROUND
  The aim of this study was to compare the long-term safety and efficacy of oral busulfan 12 mg/kg plus melphalan 140 mg/m(2) and melphalan 200 mg/m(2) as conditioning regimens for autologous stem cell transplantation in newly diagnosed patients with multiple myeloma in the GEM2000 study.
  
  
  METHODS
  The first 225 patients received oral busulfan 12 mg/kg plus melphalan 140 mg/m(2); because of a high frequency of veno-occlusive disease, the protocol was amended and a further 542 patients received melphalan 200 mg/m(2).
  
  
  RESULTS
  Engraftment and hospitalization times were similar in both groups. Oral busulfan 12 mg/kg plus melphalan 140 mg/m(2) resulted in higher transplant-related mortality (8.4% versus 3.5%; P=0.002) due to the increased frequency of veno-occlusive disease in this group. Response rates were similar in both arms. With respective median follow-ups of 72 and 47 months, the median progression-free survival was significantly longer with busulfan plus melphalan (41 versus 31 months; P=0.009), although survival was similar to that in the melphalan 200 mg/m(2) group. However, access to novel agents as salvage therapy after relapse/progression was significantly lower for patients receiving busulfan plus melphalan (43%) than for those receiving melphalan 200 mg/m(2) (58%; P=0.01).
  
  
  CONCLUSIONS
  Conditioning with oral busulfan 12 mg/kg plus melphalan 140 mg/m(2) was associated with longer progression-free survival but equivalent survival to that achieved with melphalan 200 mg/m(2) but this should be counterbalanced against the higher frequency of veno-occlusive disease-related deaths. This latter fact together with the limited access to novel salvage therapies in patients conditioned with oral busulfan 12 mg/kg plus melphalan 140 mg/m(2) may explain the absence of a survival difference. Oral busulfan was used in the present study; use of the intravenous formulation may reduce toxicity and result in greater efficacy, and warrants further investigation in myeloma patients. (Clinicaltrials.gov identifier: NCT00560053).
authors.affiliation: Hospital Universitario 12de Octubre, 28041 Madrid, Spain. jjlahuerta@telefonica.net
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lahuerta
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: Joaquin
authors.initials: J
authors.lastname: Martínez-López
authors.forename: Carlos
authors.initials: C
authors.lastname: Grande
authors.forename: Javier
authors.initials: J
authors.lastname: de la Rubia
authors.forename: Laura
authors.initials: L
authors.lastname: Rosiñol
authors.forename: Anna
authors.initials: A
authors.lastname: Sureda
authors.forename: José
authors.initials: J
authors.lastname: García-Laraña
authors.forename: Joaquín
authors.initials: J
authors.lastname: Díaz-Mediavilla
authors.forename: Miguel T
authors.initials: MT
authors.lastname: Hernández-García
authors.forename: Dolores
authors.initials: D
authors.lastname: Carrera
authors.forename: Joan
authors.initials: J
authors.lastname: Besalduch
authors.forename: Felipe
authors.initials: F
authors.lastname: de Arriba
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.forename: Lourdes
authors.initials: L
authors.lastname: Escoda
authors.forename: Javier
authors.initials: J
authors.lastname: García-Frade
authors.forename: Concepción
authors.initials: C
authors.lastname: Rivas-González
authors.forename: Adrían
authors.initials: A
authors.lastname: Alegre
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy*; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous
chemical_list: D019653:Myeloablative Agonists; D002066:Busulfan; D008558:Melphalan