Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi).
A prospective multicenter program was performed to evaluate the combination of rituximab and high-dose (hd) sequential chemotherapy delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS-maps regimen) in previously untreated patients with diffuse large B-cell lymphoma (DLB-CL) and age-adjusted International Prognostic Score (aaIPI) score 2-3. R-HDS-maps includes: (i) three APO courses; (ii) sequential administration of hd-cyclophosphamide (CY), hd-Ara-C, both supplemented with rituximab, hd-etoposide/cisplatin, PBPC harvests, following hd-CY and hd-Ara-C; (iii) hd-mitoxantrone (hd-Mito)/L-Pam + 2 further rituximab doses; (iv) involved-field radiotherapy. PBPC rescue was scheduled following Ara-C, etoposide/cisplatin and Mito/L-Pam. Between 1999 and 2004, 112 consecutive patients aged <65 years (74 score 2, 38 score 3) entered the study protocol. There were five early and two late toxic deaths. Overall 90 patients (80%) reached clinical remission (CR); at a median 48 months follow-up, 87 (78%) patients are alive, 82 (73%) in continuous CR, with 4 year overall survival (OS) and event-free survival (EFS) projections of 76% (CI 68-85%) and 73% (CI 64-81%), respectively. There were no significant differences in OS and EFS between subgroups with Germinal-Center and Activated B-cell phenotype. Thus, life expectancy of younger patients with aaIPI 2-3 DLB-CL is improved with the early administration of rituximab-supplemented intensive chemotherapy compared with the poor outcome following conventional chemotherapy.
Tarella
C
C
Dip Medicina-Oncologia Sperimentale, Divisione Universitaria di Ematologia, Torino, Italy. corrado.tarella@unito.it
Zanni
M
M
Di Nicola
M
M
Patti
C
C
Calvi
R
R
Pescarollo
A
A
Zoli
V
V
Fornari
A
A
Novero
D
D
Cabras
A
A
Stella
M
M
Comino
A
A
Remotti
D
D
Ponzoni
M
M
Caracciolo
D
D
Ladetto
M
M
Magni
M
M
Devizzi
L
L
Rosato
R
R
Boccadoro
M
M
Bregni
M
M
Corradini
P
P
Gallamini
A
A
Majolino
I
I
Mirto
S
S
Gianni
A M
AM
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000628:therapy*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D036102:Peripheral Blood Stem Cell Transplantation; D011446:Prospective Studies; D000069283:Rituximab; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D003561:Cytarabine; D000069283:Rituximab; D005047:Etoposide; D003520:Cyclophosphamide; D008942:Mitoxantrone; D002945:Cisplatin; D008558:Melphalan