title: Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkin's lymphoma: long-term results by the NHLCSG.
abstract: BACKGROUND
  There is not univocal concordance for using high-dose sequential therapy (HDS) as first-line treatment for aggressive non-Hodgkin's lymphoma (NHL). We designed this study to evaluate the usefulness of HDS followed by high-dose therapy (HDT) with autologous stem cell transplantation as front-line treatment in different subsets of aggressive NHL.
  
  
  METHODS
  Among 223 patients aged 15-60 years with aggressive, advanced stage NHL, 106 patients were randomized to VACOP-B (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) for 12 weeks (plus HDS/HDT in case of persistent disease) (arm A), and 117 patients to VACOP-B for 8 weeks plus upfront HDS/HDT (arm B).
  
  
  RESULTS
  According to the intention-to-treat analysis, the complete response rate was 75% for arm A and 72.6% for arm B. With a median follow-up of 62 months there was no difference in 7-year probability of survival (60% and 57.8%; P = 0.5), disease-free survival (DFS) (62% and 71%; P = 0.2) and progression-free survival (PFS) (44.9% and 40.9%; P = 0.7) between the two arms. Subgroup analyses confirmed that the best results in terms of survival, DFS and PFS were achieved by patients with large B-cell NHL without bone marrow (BM) involvement, independently of the treatment arm. Results were poorer in other categories of patients and poorest in patients with BM involvement.
  
  
  CONCLUSIONS
  Aggressive NHL patients do not benefit from upfront HDS/HDT.
authors.affiliation: Department of Hematology, University of Ancona, Italy. a.olivieri@ao-umbertoprimo.marche.iy
authors.forename: A
authors.initials: A
authors.lastname: Olivieri
authors.forename: G
authors.initials: G
authors.lastname: Santini
authors.forename: C
authors.initials: C
authors.lastname: Patti
authors.forename: T
authors.initials: T
authors.lastname: Chisesi
authors.forename: C
authors.initials: C
authors.lastname: De Souza
authors.forename: A
authors.initials: A
authors.lastname: Rubagotti
authors.forename: S
authors.initials: S
authors.lastname: Aversa
authors.forename: A
authors.initials: A
authors.lastname: Billio
authors.forename: A
authors.initials: A
authors.lastname: Porcellini
authors.forename: M
authors.initials: M
authors.lastname: Candela
authors.forename: R
authors.initials: R
authors.lastname: Centurioni
authors.forename: A M
authors.initials: AM
authors.lastname: Congiu
authors.forename: M
authors.initials: M
authors.lastname: Brunori
authors.forename: S
authors.initials: S
authors.lastname: Nati
authors.forename: M
authors.initials: M
authors.lastname: Spriano
authors.forename: R
authors.initials: R
authors.lastname: Vimercati
authors.forename: G
authors.initials: G
authors.lastname: Marino
authors.forename: A
authors.initials: A
authors.lastname: Contu
authors.forename: L
authors.initials: L
authors.lastname: Tedeschi
authors.forename: I
authors.initials: I
authors.lastname: Majolino
authors.forename: M
authors.initials: M
authors.lastname: Crugnola
authors.forename: M R
authors.initials: MR
authors.lastname: Sertoli
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001761:Bleomycin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016393:Lymphoma, B-Cell / Q000628:therapy*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D011241:Prednisone / Q000008:administration & dosage; D016879:Salvage Therapy; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D001761:Bleomycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone