title: High-dose therapy and autologous peripheral blood stem cells transplantation followed by a very low reduced intensity regimen with fludarabine + cyclophosphamide and allograft improve complete remission rate in de novo multiple myeloma patients.
abstract: The recent development of reduced intensity conditioning and allotransplantation (RICT) has opened a new way to assure engraftment of donor cells while reducing early transplant-related mortality. We evaluated the combination of high-dose therapy and autologous peripheral blood stem cells transplantation (APBSCT) followed by RICT to extend the benefit of allografting procedures in de novo multiple myeloma (MM) patients. Fifteen subjects with stage III MM (median age 51 years, range 40-57) received high dose melphalan (200 mg/m(2)) followed by APBSCT previously collected after cyclophosphamide (4 g/m(2)) and granulocyte colony-stimulating factor (G-CSF). After 3-4 months from APBSCT, the patients underwent RICT, consisting of fludarabine 30 mg/m(2) + cyclophosphamide 300 mg/m(2) on days -4, -3, and -2. Acute graft-versus-host disease (GVHD) occurred in 2 patients; 6 patients developed chronic GVHD; 4 patients developed CMV antigenemia and were treated pre-emptively with ganciclovir. No transplant related mortality was shown. Response was simultaneously measured by both electrophoresis (EP) and immunofixation (IF); when IF was negative, patients were classified in complete remission (CR) and when it remained positive, near CR (nCR). After a median follow up of 44 months post APBSCT, 100 and 43% of patients are still alive and progression-free, respectively. Overall, the CR + nCR rate after dose-reduced allograft was enhanced from 26.7 to 73.3%. A correlation not statistically significant between GVHD and remission was found. In conclusion, an up-front tandem strategy with a very low reduced intensity-conditioning regimen for allografting following autografting is feasible and induces high CR/nCR rate in MM.
authors.affiliation: Bone Marrow Transplant Unit, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy. massimartino@tin.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Martino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Console
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Irrera
authors.forename: Giulia
authors.initials: G
authors.lastname: Praticò
authors.forename: Caterina
authors.initials: C
authors.lastname: Stelitano
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Callea
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.forename: Eugenia
authors.initials: E
authors.lastname: Quartarone
authors.forename: Caterina
authors.initials: C
authors.lastname: Musolino
authors.forename: Eugenio
authors.initials: E
authors.lastname: Piro
authors.forename: Maura
authors.initials: M
authors.lastname: Brugiatelli
authors.forename: Pasquale
authors.initials: P
authors.lastname: Iacopino
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy*; D019653:Myeloablative Agonists; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan