A multicenter randomized trial by Italian Lymphoma Intergroup comparing high dose chemotherapy with autologous stem cell transplantation vs intensified chemotherapy MegaCEOP in high risk diffuse large cell lymphoma No difference in outcome and toxicity
Vitolo, Umberto; Liberati, Anna Marina; Deliliers, Giorgio Lambertenghi; Calvi, Roberta; Baldini, Luca; Bertini, Marilena; Brugiatelli, Maura; Cabras, Maria Giuseppina; Di Renzo, Nicola; Federico, Massimo; Freilone, Roberto; Parvis, Guido; Pavone, Enzo; Petrini, Mar
Blood 98(11 Part 1): 725a-726a
2001
ISSN/ISBN: 0006-4971
Accession: 034298629
Introduction: high risk DLCL fared poorly with standard chemotherapy. High dose chemotherapy was reported to give better results compared to standard chemotherapy in randomized studies. Promising results were observed with intensified chemotherapy with G-CSF. No data are yet available comparing these two approaches. A multicenter study was performed by the ILI to compare feasibility, toxicity and outcome of HDS regimen with ASCT vs an outpatient intensified chemotherapy regimen (MegaCEOP). Patients and methods: from January 1996 to September 2000, 131 patients (pts) <60 years with DLCL with intermediate-high (IH) or high (H) risk according to age-adjusted IPI and/or bone marrow (BM) involvement were enrolled. They were randomized to: group A HDS (debulking with APO followed by intensification with Cyclophosphamide 7 g/m2+Methotrexate 8 g/m2 Vincristine 1.4 mg/m2+VP-16 2 g/m2+-2 DHAP in BM+pts)+ASCT (Mitoxantrone 60 mg/m2+Melphalan 180 mg/m2); group B MegaCEOP (Cyclophosphamide 1200 mg/m2+Epirubicine 110 mg/m2+Vincristine 1.4 mg/m2 day 1 and Prednisone 40 mg/m2 days 1 to 5) 6 or 8 courses (BM+pts) every 14 days with G-CSF 5 mug/Kg days 2-10. Results: four pts were excluded (2 major violations and 3 pts not yet evaluable): 124 pts have been evaluated so far: 60 randomized to HDS+ASCT and 64 to MegaCEOP. Clinical characteristics were balanced between the 2 groups; median age 43 years (18-60), 61% had B symptoms, 60% PS >1, 74% LDH >normal, 50% bulky disease, 21% stage II, 22% stage III and 57% stage IV, 23% >1 extranodal sites and 25% were BM+. Sixty-three% were at IH risk and 37% at H risk. Complete remission (CR) rate was superimposable between the two groups: group A 60% vs group B 69%. CR rate was not affected by BM involvement, stage, bulky disease or LDH level. Pts at H risk had a significant lower CR rate than those at IH risk: 50% vs 71%, p<0.03. There was no difference in response rate between A and B in each of the IPI risk group. With a median follow up of 36 months no differences in the outcome were observed between the two groups. DFS, OS and FFS rates at three years were respectively: group A 82%, 60%, 46% vs group B 64%, 51%, 44%. FFS rates were not different between group A and B in pts without BM involvement (group A 47% vs B 51%) whereas pts with BM involvement did significantly better if treated with HDS+ASCT (FFS 43% vs 28%, p<0.05). Fifteen pts did not complete the program: 10 group A(3 toxicities and 7 progressions), 5 group B (2 toxicities and 3 progressions). Severe toxicities (WHO >2) were as follows (A vs B): cardiac 5% vs 1%; peripheral neuropathy 5% vs 5%; infections 18% vs 9% and mucositis 30% vs 3%. Four pts died of toxicity: two (HDS) due to aspergillosis and bacterial pneumonia and two (MegaCEOP) due to sepsis. Two secondary ANLL and MDS were observed at 23 and 30 months after ASCT in group A. Conclusions: HDS+ASCT or an intensified outpatient chemotherapy (MegaCEOP) are effective in high risk DLCL and feasible in a cooperative setting without severe toxicity. So far, outcome and toxicities did not seem to be different in both treatment groups.