title: Autologous peripheral blood stem cell transplantation as first line treatment of multiple myeloma: an Italian Multicenter Study.
abstract: OBJECTIVE
  The outcome of patients with multiple myeloma (MM) has not changed markedly since the introduction of melphalan and prednisone. In recent years several studies have investigated the role of intensive therapy followed by infusion of autologous peripheral blood stem cells (PBSC) together with the administration of hematopoietic growth factors. In this study we evaluated the feasibility and efficacy of a PBSC transplantation program for patients with de novo MM in a multicenter setting.
  
  
  METHODS
  In a non-randomized controlled trial 52 patients with de novo MM from 6 Italian centers underwent a three phase treatment strategy including 3 cycles of VAD-like chemotherapy for initial debulking, followed by high-dose cyclophosphamide (HD-CY) and collection of PBSC, that were transplanted after a conditioning regimen with melphalan plus busulfan. Maintenance treatment was a conventional dose of interferon, given until relapse. Actuarial survival and response duration curves were plotted according to Kaplan and Meier's method; the groups were compared using the log rank test. Response rates were compared by the c(2) test; multivariate analysis was performed according to the stepwise regression model.
  
  
  RESULTS
  Overall 39/52 (75%) of patients responded, with a complete remission (CR) rate of 31%. After a median follow-up of 55 months, median duration of event-free survival (EFS) and overall survival (OS) are 21 and 57 months, with 24% and 48% probabilities of being event-free and alive after 6 years, respectively. Among the group of 39 responders, CR was significantly associated with prolonged response and survival (2 deaths and 6 relapses/16 patients) as compared with PR (11 deaths and 15 relapses/23 patients), and remained the only significant variable also in a multivariate analysis. Myelosuppression did not protract beyond one week in transplanted patients; extra-hematologic toxicity was very low.
  
  
  CONCLUSIONS
  This multicenter study confirms the feasibility of an aggressive approach to de novo MM patients. Additional confirmation is given of the increased rate of CR, and the significant prolonged survival observed in complete responders. In this experience the association melphalan plus busulfan was shown to be effective, at least as part of conditioning regimens, in the transplant strategy.
authors.affiliation: Divisione di Ematologia, Ospedale S. Eugenio, piazzale dell'Umanesimo, 00144 Rome, Italy. md4775@mclink.it.
authors.forename: M
authors.initials: M
authors.lastname: Tribalto
authors.forename: S
authors.initials: S
authors.lastname: Amadori
authors.forename: L
authors.initials: L
authors.lastname: Cudillo
authors.forename: T
authors.initials: T
authors.lastname: Caravita
authors.forename: G
authors.initials: G
authors.lastname: Del Poeta
authors.forename: G
authors.initials: G
authors.lastname: Meloni
authors.forename: G
authors.initials: G
authors.lastname: Avvisati
authors.forename: M T
authors.initials: MT
authors.lastname: Petrucci
authors.forename: A
authors.initials: A
authors.lastname: Pulsoni
authors.forename: G
authors.initials: G
authors.lastname: Leone
authors.forename: S
authors.initials: S
authors.lastname: Sica
authors.forename: M
authors.initials: M
authors.lastname: Martelli
authors.forename: A
authors.initials: A
authors.lastname: Tabilio
authors.forename: G
authors.initials: G
authors.lastname: Fioritoni
authors.forename: I
authors.initials: I
authors.lastname: Majolino
authors.forename: F
authors.initials: F
authors.lastname: Mandelli
mesh_terms: D000328:Adult; D000367:Age Factors; D018952:Antigens, CD34 / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity; D001781:Blood Component Removal; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity; D003561:Cytarabine / Q000008:administration & dosage / Q000633:toxicity; D003907:Dexamethasone / Q000008:administration & dosage / Q000633:toxicity; D018572:Disease-Free Survival; D017707:Erythrocyte Transfusion; D005069:Evaluation Studies as Topic; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007239:Infections / Q000209:etiology; D007558:Italy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000628:therapy*; D019653:Myeloablative Agonists / Q000627:therapeutic use / Q000633:toxicity; D009504:Neutrophils; D010976:Platelet Count; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D013234:Stem Cells; D015996:Survival Rate; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D018952:Antigens, CD34; D019653:Myeloablative Agonists; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D003907:Dexamethasone; D003520:Cyclophosphamide