Negative selection of peripheral blood stem cells to support a tandem autologous transplantation programme in multiple myeloma.
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.
Barbui
Anna Maria
AM
Divisione di Ematologia, Radioterapia and Centro Trasfusionale, Ospedali Riuniti, Bergamo, Italy.
Galli
Monica
M
Dotti
Gianpietro
G
Belli
Nadia
N
Borleri
Gianmaria
G
Gritti
Giovanna
G
Bellavita
Piermario
P
Viero
Piera
P
Comotti
Benedetto
B
Barbui
Tiziano
T
Rambaldi
Alessandro
A
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