title: Three-step high-dose sequential chemotherapy in patients with newly diagnosed multiple myeloma.
abstract: OBJECTIVE
  High-dose chemotherapy (HDT) with autologous peripheral blood progenitor cell (PBPC) transplant has been increasingly used for newly diagnosed multiple myeloma (MM) in recent years. Presently available results suggest an improvement in the complete remission rate and survival as compared to conventional chemotherapy. However, there is no plateau in the survival curves, and experiments with new treatment schedules and conditioning regimens are warranted.
  
  
  METHODS
  In a non-randomised controlled trial, 20 patients underwent three-step HDT following conventional vincristine/doxorubicin/dexamethasone (VAD)-based induction. In the intensification phase patients received high-dose cyclophosphamide (HD-CY), high-dose etoposide (HD-VP), and mitoxantrone (NOV) plus melphalan (L-PAM) with haemopoietic rescue. Maintenance treatment with interferon was given until relapse. Actuarial overall survival (OS) and event-free survival (EFS) curves were plotted according to the method of Kaplan and Meier. In five of the eight patients achieving complete remission (CR), the molecular disease was monitored by polymerase chain reaction technique (PCR).
  
  
  RESULTS
  Overall 18/20 (90%) patients responded, with a CR rate of 40%. After an average follow-up of 40 months, median EFS and OS are 25.5 and 44.6 months, respectively. Monoclonal cells were detectable in the post-treatment bone marrow and in the aphereses of the five CR patients monitored by PCR.
  
  
  CONCLUSIONS
  The present three-step HDT regimen, including conditioning with mitoxantrone and melphalan, proved to be feasible and safe. Our results are in agreement with the hypothesis that HDT results in an increased remission rate and in prolonged survival in newly diagnosed MM, but a cure is unlikely.
authors.affiliation: Department of Internal Medicine, University of Genova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ballestrero
authors.forename: Fabio
authors.initials: F
authors.lastname: Ferrando
authors.forename: Maurizio
authors.initials: M
authors.lastname: Miglino
authors.forename: Marino
authors.initials: M
authors.lastname: Clavio
authors.forename: Roberta
authors.initials: R
authors.lastname: Gonella
authors.forename: Anna
authors.initials: A
authors.lastname: Garuti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Grasso
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ghio
authors.forename: Enrico
authors.initials: E
authors.lastname: Balleari
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
authors.forename: Franco
authors.initials: F
authors.lastname: Patrone
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D002999:Clone Cells / Q000473:pathology; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004273:DNA, Neoplasm / Q000032:analysis; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000628:therapy; D012074:Remission Induction / Q000379:methods; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D004273:DNA, Neoplasm; D014750:Vincristine; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D008942:Mitoxantrone; D008558:Melphalan