TY - JOUR
T1 - 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
T2 - A multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi)
AU - Tarella, C.
AU - Zanni, M.
AU - Di Nicola, M.
AU - Patti, C.
AU - Calvi, R.
AU - Pescarollo, A.
AU - Zoli, V.
AU - Fornari, A.
AU - Novero, D.
AU - Cabras, A.
AU - Stella, M.
AU - Comino, A.
AU - Remotti, D.
AU - Ponzoni, M.
AU - Caracciolo, D.
AU - Ladetto, M.
AU - Magni, M.
AU - Devizzi, L.
AU - Rosato, R.
AU - Boccadoro, M.
AU - Bregni, M.
AU - Corradini, P.
AU - Gallamini, A.
AU - Majolino, I.
AU - Mirto, S.
AU - Gianni, A. M.
N1 - Funding Information:
Investigators from the following Institutions in Italy contributed to the trial: Divisione Universitaria di Ematologia, A.S.O. S. Giovanni B., Torino: C Tarella, D Caracciolo, ML, I Ricca, MZ, MB; Divisione di Oncologia Medica and Divisione di Ematologia, Istituto Nazionale Tumori, Milano: AMG, PC, MDiN, MM, LD, F Zallio; Divisione di Ematologia, A.S.O. V.Cervello (Palermo): SM, CP, R Scimé, AC; Divisione di Ematologia, A.S.O. S. Croce, Cuneo: AG, RC, C Castellino; Bone Marrow Trasplanta-tion Unit, Istituto Scientifico H. S. Raffaele (Milano): AP, MB; Divisione di Ematologia, A.S.O. S. Camillo-Forlanini, Roma: IM, VZ; Istituti di Anatomia Patologica di, Università di Torino: G Inghirami, DN, AF; Istituto Nazionale Tumori, Milano: A Carbone, AC; A.S.O. V. Cervello, Palermo: A Rizzo, MS; A.S.O. S. Croce, Cuneo: AC; A.S.O. S. Camillo-Forlanini, Roma: RP, DR; Istituto Scientifico H. S. Raffaele, Milano: C Doglioni, M Ponzoni. This work was supported in part by grants from: Ministero dell’Istru-zione, dell’Università e della Ricerca (MIUR); the Michelangelo Foundation for Advances in Cancer Research and Treatment; the Piedmont Regional Government (Regione Piemonte). We thank Professor Giorgio Inghirami for helpful suggestions and assistance in the pathological review and immunohistochemical reassessment.
PY - 2007/8
Y1 - 2007/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34447626101&partnerID=8YFLogxK
U2 - 10.1038/sj.leu.2404781
DO - 10.1038/sj.leu.2404781
M3 - Article
SN - 0887-6924
VL - 21
SP - 1802
EP - 1811
JO - Leukemia
JF - Leukemia
IS - 8
ER -
