title: Negative selection of peripheral blood stem cells to support a tandem autologous transplantation programme in multiple myeloma.
abstract: We recently described a two-step negative selection procedure whereby peripheral blood stem cells (PBSCs) were efficiently purged of contaminating neoplastic cells by a combination of monoclonal antibodies. Here, we report 60 newly diagnosed multiple myeloma (MM) patients treated with a double transplant programme and randomized to receive either unmanipulated or in vitro purged PBSCs. We demonstrated that this technique is feasible and safe without significant loss of either CD34+ or CD3+ cells. Haematological engraftment and immunological reconstitution were rapid without treatment-related mortality. Using polymerase chain reaction (PCR), we compared the level of minimal residual disease (MRD) in PBSC before and after in vitro purging and in vivo after transplant. A median of one tumour cell per 10(2) normal cells (range 10(1)-10(5)) was seen in the unmanipulated aphereses with a 3-4 log reduction after manipulation in vitro. However, despite this tumour debulking, all patients remained PCR positive in vivo. At 3 years, the estimated event-free survival was 40% in the control arm and 72% in the experimental arm (P = 0.05), whereas the estimated overall survival was 83% in both arms. This suggests that autologous transplantation using efficiently purged PBSCs can be performed safely, but confirms the need for innovative protocols for MRD eradication in vivo.
authors.affiliation: Divisione di Ematologia, Radioterapia and Centro Trasfusionale, Ospedali Riuniti, Bergamo, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Barbui
authors.forename: Monica
authors.initials: M
authors.lastname: Galli
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Dotti
authors.forename: Nadia
authors.initials: N
authors.lastname: Belli
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Borleri
authors.forename: Giovanna
authors.initials: G
authors.lastname: Gritti
authors.forename: Piermario
authors.initials: P
authors.lastname: Bellavita
authors.forename: Piera
authors.initials: P
authors.lastname: Viero
authors.forename: Benedetto
authors.initials: B
authors.lastname: Comotti
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
mesh_terms: D000328:Adult; D000368:Aged; D001781:Blood Component Removal / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000401:mortality / Q000601:surgery*; D018365:Neoplasm, Residual; D009360:Neoplastic Cells, Circulating; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D015996:Survival Rate; D014182:Transplantation, Autologous