title: High-dose sequential chemoradiotherapy, a widely applicable regimen, confers survival benefit to patients with high-risk multiple myeloma.
abstract: OBJECTIVE
  To assess the toxicity, efficacy, and applicability of high-dose therapy with bone marrow and/or peripheral-blood autotransplantation in high-risk, previously untreated patients with multiple myeloma.
  
  
  METHODS
  Thirteen consecutive patients with high-labeling index (LI) multiple myeloma received a novel high-dose sequential (HDS) regimen consisting in the high-dose administration of cyclophosphamide (7 g/m2) followed by vincristine (1.4 mg/m2) plus methotrexate (8 g/m2 with leucovorin rescue), etoposide (2 g/m2) and, finally, total-body irradiation (TBI; 10 Gy) plus melphalan (120 mg/m2) with autografting of peripheral-blood hematopoietic progenitor cells. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 5 micrograms/kg/d) was continuously infused after cyclophosphamide and etoposide both to accelerate hematopoietic recovery and to expand/mobilize the hematopoietic progenitor-cell pool.
  
  
  RESULTS
  Among 13 patients, 12 completed the program; 10 (or 77%) achieved a complete response and five are alive and disease-free after a median follow-up duration of 36 months (range, 24 to 52). The durations of both freedom from progression (FFP; median, 38 months) and overall survival (OS; median, 41 months) were significantly superior in the 13 HDS-treated patients as compared with 19 well-matched historical controls.
  
  
  CONCLUSIONS
  HDS emerges as a highly effective, well-tolerated, and widely accessible regimen capable of imparting a survival benefit to patients with high-LI multiple myeloma. Larger studies using this or similar programs in standard-risk myeloma are clearly warranted.
authors.affiliation: Cristina Gandini Bone Marrow Transplantation Unit, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Gianni
authors.forename: C
authors.initials: C
authors.lastname: Tarella
authors.forename: M
authors.initials: M
authors.lastname: Bregni
authors.forename: S
authors.initials: S
authors.lastname: Siena
authors.forename: F
authors.initials: F
authors.lastname: Lombardi
authors.forename: L
authors.initials: L
authors.lastname: Gandola
authors.forename: D
authors.initials: D
authors.lastname: Caracciolo
authors.forename: A
authors.initials: A
authors.lastname: Stern
authors.forename: G
authors.initials: G
authors.lastname: Bonadonna
authors.forename: M
authors.initials: M
authors.lastname: Boccadoro
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
chemical_list: D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor