TORNA ALL’ELENCO

Rituximab dose-dense chemotherapy followed by intensified high-dose chemotherapy and autologous stem cell transplantation (HDC+ASCT) significantly reduces the risk of progression compared to standard rituximab dose-dense chemotherapy as first line treatment in young patients with high-risk (AA-IPI 2-3) diffuse large B-cell lymphoma (DLBCL): Final results of phase III randomized trial DLCL04 of the fondazione Italiana linfomi (FIL) in Blood

2012
AOU Città della Salute di Torino

Tipo pubblicazione

Conference Abstract

Autori/Collaboratori (28)Vedi tutti...

Vitolo U

Chiappella A

Brusamolino E


et alii...

Abstract

Introduction.: The prognosis of young DLBCL patients at high risk treated with standard R-CHOP is still rather poor. The role of intensified HDC+ASCT in first line treatment is still a matter of debate in the Rituximab era. The FIL planned a prospective randomized phase III trial with a 2x2 factorial design aimed at investigating the possible benefit of intensification with R-HDC+ASCT after R-dose-dense chemotherapy delivered at two different level of dose (R-CHOP14/R-MegaCHOP14). Patients and methods. The primary end-point was to increase 2-year Progression Free Survival (PFS) from 50% of the standard dose-dense arm (R-dose-dense chemotherapy) to 65% in the experimental arm (R-dose-dense chemotherapy followed by R-HDC +ASCT). Secondary end-point was the comparison between two different schemes of dose dense chemotherapy, R-CHOP14 and R-MegaCHOP14. Inclusion criteria were: age 18-65; untreated DLBCL; age-adjusted IPI (aa-IPI) score 2 or 3. Patients were stratified according to aa-IPI and randomized at diagnosis to receive: R-CHOP14 x 8 cycles; R-MegaCHOP14 (1200 mg/sqm Cyclophosphamide, 70 mg/sqm Doxorubicin, standard dose Vincristine and Prednisone) x 6; R-CHOP14 x 4 + R-HDC (Rituximab + High Dose Cytarabine + Mitoxantrone + Dexamethasone) followed by BEAM and ASCT; R-MegaCHOP14 x 4 + R-HDC + BEAM and ASCT. G-CSF support was mandatory. Central nervous system prophylaxis was done according to the Italian Society of Hematology guidelines. Results.: From June 2005 to September 2010, 412 patients were enrolled. Histology was centrally reviewed in 90% of cases. Thirteen patients were excluded because of different histological subtypes in 10 and active hepatitis HCV and HBV in 3. 399 patients were eligible and randomized: 199 to R-HDC+ASCT and 200 to R-dose-dense chemotherapy without ASCT; according to the type of chemotherapy 203 were randomized to RCHOP14 and 196 to R-MegaCHOP14. All patients were evaluable for analysis. Clinical characteristics were: median age

Keywords

rituximab; cyclophosphamide; dexamethasone; granulocyte colony stimulating factor; mitoxantrone; cytarabine; prednisone; vincristine; doxorubicin; lactate dehydrogenase; risk; dose densification; human; autologous stem cell transplantation; large cell lymphoma; patient; chemotherapy; drug megadose; society; hematology; arm; remission; diagnosis; bone marrow; factorial design; progression free survival; prognosis; overall survival; proportional hazards model; gender; follow up; central nervous system; prophylaxis; hepatitis; normal value; death; toxicity; histology; relapse; electrocorticography; cerebrospinal fluid; survival rate;