A comparison of allografting with autografting for newly diagnosed myeloma.
BACKGROUND
In this trial of the treatment of newly diagnosed multiple myeloma, we compared a protocol that entailed a hematopoietic stem-cell autograft followed by an allograft from an HLA-identical sibling with a protocol of tandem autografts.


METHODS
We enrolled 162 consecutive patients with newly diagnosed myeloma who were 65 years of age or younger and who had at least one sibling. All patients were initially treated with vincristine, doxorubicin, and dexamethasone, followed by melphalan and autologous stem-cell rescue. Patients with an HLA-identical sibling then received nonmyeloablative total-body irradiation and stem cells from the sibling. Patients without an HLA-identical sibling received two consecutive myeloablative doses of melphalan, each of which was followed by autologous stem-cell rescue. The primary end points were overall survival and event-free survival.


RESULTS
After a median follow-up of 45 months (range, 21 to 90), the median overall survival and event-free survival were longer in the 80 patients with HLA-identical siblings than in the 82 patients without HLA-identical siblings (80 months vs. 54 months, P=0.01; and 35 months vs. 29 months, P=0.02, respectively). Among patients who completed their assigned treatment protocols, treatment-related mortality did not differ significantly between the double-autologous-transplant group (46 patients) and the autograft-allograft group (58 patients, P=0.09), but disease-related mortality was significantly higher in the double-autologous-transplant group (43% vs. 7%, P<0.001). The cumulative incidence rates of grades II, III, and IV graft-versus-host disease (GVHD) combined and of grade IV GVHD in the autograft-allograft group were 43% and 4%, respectively. Overall, 21 of 58 patients (36%) were in complete remission after a median follow-up of 38 months (range, 10 to 72) after allografting. Of the 46 patients who received two autografts, 25 (54%) died.


CONCLUSIONS
Among patients with newly diagnosed myeloma, survival in recipients of a hematopoietic stem-cell autograft followed by a stem-cell allograft from an HLA-identical sibling is superior to that in recipients of tandem stem-cell autografts. (ClinicalTrials.gov number, NCT00415987 [ClinicalTrials.gov].).
Bruno
Benedetto
B
San Giovanni Battista Hospital, University of Turin, Turin, Italy. benedetto.bruno@unito.it
Rotta
Marcello
M
Patriarca
Francesca
F
Mordini
Nicola
N
Allione
Bernardino
B
Carnevale-Schianca
Fabrizio
F
Giaccone
Luisa
L
Sorasio
Roberto
R
Omedè
Paola
P
Baldi
Ileana
I
Bringhen
Sara
S
Massaia
Massimo
M
Aglietta
Massimo
M
Levis
Alessandro
A
Gallamini
Andrea
A
Fanin
Renato
R
Palumbo
Antonio
A
Storb
Rainer
R
Ciccone
Giovannino
G
Boccadoro
Mario
M
D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000145:classification / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy*; D015999:Multivariate Analysis; D035781:Siblings; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous