Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo.
Despite recent advances, allografting remains the only potential cure for myeloma. From July 1999 to June 2005, 100 newly diagnosed patients younger than 65 years were enrolled in a prospective multicenter study. First-line treatment included vincristin, adriamycin, and dexamethasone (VAD)-based induction chemotherapy, a cytoreductive autograft (melphalan 200 mg/m(2)) followed by a single dose of nonmyeloablative total body irradiation and allografting from an human leukocyte antigen (HLA)-identical sibling. Primary end points were the overall survival (OS) and event-free survival (EFS) from diagnosis. After a median follow-up of 5 years, OS was not reached, and EFS was 37 months. Incidences of acute and chronic graft-versus-host disease (GVHD) were 38% and 50%, respectively. Complete remission (CR) was achieved in 53% of patients. Profound cytoreduction (CR or very good partial remission) before allografting was associated with achievement of posttransplantation CR (hazard ratio [HR] 2.20, P = .03) and longer EFS (HR 0.33, P < .01). Conversely, development of chronic GVHD was not correlated with CR or response duration. This tandem transplantation approach allows prolonged survival and long-term disease control in patients with reduced tumor burden at the time of allografting. We are currently investigating the role of "new drugs" in intensifying pretransplantation cytoreduction and posttransplantation graft-versus-myeloma effects to further improve clinical outcomes. (http://ClinicalTrials.gov; NCT-00702247.).
Bruno
Benedetto
B
Division of Hematology, S Giovanni Battista Hospital, University of Torino, Torino, Italy. benedetto.bruno@unito.it
Rotta
Marcello
M
Patriarca
Francesca
F
Mattei
Daniele
D
Allione
Bernardino
B
Carnevale-Schianca
Fabrizio
F
Sorasio
Roberto
R
Rambaldi
Alessandro
A
Casini
Marco
M
Parma
Matteo
M
Bavaro
Pasqua
P
Onida
Francesco
F
Busca
Alessandro
A
Castagna
Luca
L
Benedetti
Edoardo
E
Iori
Anna Paola
AP
Giaccone
Luisa
L
Palumbo
Antonio
A
Corradini
Paolo
P
Fanin
Renato
R
Maloney
David
D
Storb
Rainer
R
Baldi
Ileana
I
Ricardi
Umberto
U
Boccadoro
Mario
M
D000328:Adult; D000368:Aged; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D016879:Salvage Therapy; D016019:Survival Analysis; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome