Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study.
OBJECTIVE
We performed a prospective, randomized study of single (arm A) versus double (arm B) autologous stem-cell transplantation (ASCT) for younger patients with newly diagnosed multiple myeloma (MM).


METHODS
A total of 321 patients were enrolled onto the study and were randomly assigned to receive either a single course of high-dose melphalan at 200 mg/m2 (arm A) or melphalan at 200 mg/m2 followed, after 3 to 6 months, by melphalan at 120 mg/m2 and busulfan at 12 mg/kilogram (arm B).


RESULTS
As compared with assignment to the single-transplantation group (n = 163 patients), random assignment to receive double ASCT (n = 158 patients) significantly increased the probability to attain at least a near complete response (nCR; 33% v 47%, respectively; P = .008), prolonged relapse-free survival (RFS) duration of 18 months (median, 24 v 42 months, respectively; P < .001), and significantly extended event-free survival (EFS; median, 23 v 35 months, respectively; P = .001). Administration of a second transplantation and of novel agents for treating sequential relapses in up to 50% of patients randomly assigned to receive a single ASCT likely contributed to prolong the survival duration of the whole group, whose 7-year rate (46%) was similar to that of the double-transplantation group (43%; P = .90). Transplantation-related mortality was 3% in arm A and 4% in arm B (P = .70).


CONCLUSIONS
In comparison with a single ASCT as up-front therapy for newly diagnosed MM, double ASCT effected superior CR or nCR rate, RFS, and EFS, but failed to significantly prolong overall survival. Benefits offered by double ASCT were particularly evident among patients who failed at least nCR after one autotransplantation.
Cavo
Michele
M
Istituto di Ematologia ed Oncologia Medica [Seràgnoli], Università di Bologna, Bologn, Italy. mcavo@med.unibo.it
Tosi
Patrizia
P
Zamagni
Elena
E
Cellini
Claudia
C
Tacchetti
Paola
P
Patriarca
Francesca
F
Di Raimondo
Francesco
F
Volpe
Ettore
E
Ronconi
Sonia
S
Cangini
Delia
D
Narni
Franco
F
Carubelli
Affra
A
Masini
Luciano
L
Catalano
Lucio
L
Fiacchini
Mauro
M
de Vivo
Antonio
A
Gozzetti
Alessandro
A
Lazzaro
Antonio
A
Tura
Sante
S
Baccarani
Michele
M
D000971:Antineoplastic Combined Chemotherapy Protocols; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000401:mortality / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000379:methods*; D014182:Transplantation, Autologous / Q000379:methods*; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D008558:Melphalan