Randomized trials of induction therapy followed by HDT/ASCT consolidation in newly diagnosed previously untreated aggressive lymphomas
Trial . | Protocol . | Patient characteristics . | Included diseases . | Significant results . |
|---|---|---|---|---|
| Gianni et al58 (1997) | MACOP-B vs sequential HDT/ASCT | 98 patients, aged 17-60 y, stage I (bulky), II (bulky), III, IV | WF* groups G, H | 7-y EFS: HDT 76% vs MACOP-B 49% (P = .004); 7-y OS†: ASCT 81% vs MACOP-B 55% (P = NS) |
| Santini et al59 (1998) | VACOP-B plus salvage DHAP vs VACOP-B plus HDT/ASCT | 124 patients, aged 15-60 y, stage II (bulky), III, IV | WF groups D, E, F, G, H, I, J | No difference in DFS and OS |
| Haioun et al61 (2000) | Induction with either ACVB or NCVB; patients in CR randomized to: consolidation with MTX, ifosfamide, L-asparaginase and Ara-C vs MTX and HDT/ASCT | 236 patients, aged <55 y, stage I-IV, at least one poor prognostic variable (poor PS, multiple extranodal sites, bulky disease, BM, CNS, Burkitt or lymphoblastic) | WF groups D, E, F, G, H, I, J (73% were F, G, H) | Prospective analysis: no difference in DFS and OS; Retrospective analysis on IPI HI/H-risk patients: 8-y DFS: ASCT 55% vs chemo 39% (P = .02); 8-y OS: ASCT 64% vs chemo 49% (P = .04) |
| Kluin-Nelemans et al60 (2001) | Induction with 3 cycles CHVmP/BV; patients in CR/PR with negative BM randomized to: 3 cycles CHVmP/BV HDT/ASCT vs 5 cycles CHVmP/BV | 311 patients, aged 15-65 y, stage I (bulky), II-IV | WF groups D, E, F, G (51% were DLBCL) | No difference in FFP and OS |
| Gisselbrecht et al62 (2002) | 4 cycles ACVBP, 2 cycles HD MTX, 4 cycles EI, 2 cycles Ara-C vs 1 cycle CEOP, 2 cycles ECVBP, HDT/ASCT | 370 patients, aged 15-60 y, stage I-IV, at least 2 IPI risk factors | REAL/WHO: DLBCL (61%), PTCL, lymphoblastic, Burkitt, diffuse aggressive NOS | 5-y EFS: ASCT 52% vs ACVBP 39% (P = .01); 5-y OS: ASCT 46% vs ACVBP 60% (P = .007) |
| Milpied et al66 (2004) | 4 cycles CHOP; patients in CR/PR receive 4 additional cycles vs 2 cycles CEEP; patients in CR/PR receive 1 cycle MC; HDT/ASCT | 197 patients, aged 15-60 y, stage II (bulky), III, IV; aaIPI L, LI, or HI | WF groups D, E, F, G, H (75% were DLBCL) | Prospective analysis by ITT: 5-y EFS: ASCT 55% vs CHOP 37% (P = 0.037); 5-y OS: HDT 71% vs CHOP 56% (P = NS); Retrospective analysis on IPI HI-risk patients: 5-y EFS: ASCT 56% vs CHOP 28% (P = .003); 5-y OS: HDT 74% vs CHOP 44% (P = .001) |
Trial . | Protocol . | Patient characteristics . | Included diseases . | Significant results . |
|---|---|---|---|---|
| Gianni et al58 (1997) | MACOP-B vs sequential HDT/ASCT | 98 patients, aged 17-60 y, stage I (bulky), II (bulky), III, IV | WF* groups G, H | 7-y EFS: HDT 76% vs MACOP-B 49% (P = .004); 7-y OS†: ASCT 81% vs MACOP-B 55% (P = NS) |
| Santini et al59 (1998) | VACOP-B plus salvage DHAP vs VACOP-B plus HDT/ASCT | 124 patients, aged 15-60 y, stage II (bulky), III, IV | WF groups D, E, F, G, H, I, J | No difference in DFS and OS |
| Haioun et al61 (2000) | Induction with either ACVB or NCVB; patients in CR randomized to: consolidation with MTX, ifosfamide, L-asparaginase and Ara-C vs MTX and HDT/ASCT | 236 patients, aged <55 y, stage I-IV, at least one poor prognostic variable (poor PS, multiple extranodal sites, bulky disease, BM, CNS, Burkitt or lymphoblastic) | WF groups D, E, F, G, H, I, J (73% were F, G, H) | Prospective analysis: no difference in DFS and OS; Retrospective analysis on IPI HI/H-risk patients: 8-y DFS: ASCT 55% vs chemo 39% (P = .02); 8-y OS: ASCT 64% vs chemo 49% (P = .04) |
| Kluin-Nelemans et al60 (2001) | Induction with 3 cycles CHVmP/BV; patients in CR/PR with negative BM randomized to: 3 cycles CHVmP/BV HDT/ASCT vs 5 cycles CHVmP/BV | 311 patients, aged 15-65 y, stage I (bulky), II-IV | WF groups D, E, F, G (51% were DLBCL) | No difference in FFP and OS |
| Gisselbrecht et al62 (2002) | 4 cycles ACVBP, 2 cycles HD MTX, 4 cycles EI, 2 cycles Ara-C vs 1 cycle CEOP, 2 cycles ECVBP, HDT/ASCT | 370 patients, aged 15-60 y, stage I-IV, at least 2 IPI risk factors | REAL/WHO: DLBCL (61%), PTCL, lymphoblastic, Burkitt, diffuse aggressive NOS | 5-y EFS: ASCT 52% vs ACVBP 39% (P = .01); 5-y OS: ASCT 46% vs ACVBP 60% (P = .007) |
| Milpied et al66 (2004) | 4 cycles CHOP; patients in CR/PR receive 4 additional cycles vs 2 cycles CEEP; patients in CR/PR receive 1 cycle MC; HDT/ASCT | 197 patients, aged 15-60 y, stage II (bulky), III, IV; aaIPI L, LI, or HI | WF groups D, E, F, G, H (75% were DLBCL) | Prospective analysis by ITT: 5-y EFS: ASCT 55% vs CHOP 37% (P = 0.037); 5-y OS: HDT 71% vs CHOP 56% (P = NS); Retrospective analysis on IPI HI-risk patients: 5-y EFS: ASCT 56% vs CHOP 28% (P = .003); 5-y OS: HDT 74% vs CHOP 44% (P = .001) |
MACOP-B indicates methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin; HDT, high-dose therapy; ASCT, autologous stem cell transplantation; EFS, event-free survival; OS, overall survival; NS, not significant; VACOP-B, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin; DHAP, dexamethasone, cytarabine, cisplatin; DFS, disease-free survival; ACVB, doxorubicin, cyclophosphamide, vindesine, bleomycin; NCVB, mitoxantrone, cyclophosphamide, vinblastine, bleomycin; CR, complete response; MTX, methotrexate; Ara C, cytarabine; PS, performance status; BM, bone marrow; CNS, central nervous system; IPI, International Prognostic Index; H/HI, high/high intermediate; CHVmP/BV, cyclophosphamide, doxorubicin, teniposide, prednisone, bleomycin, vincristine; PR, partial response; FFP, free from progression; ACVBP, doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone; HD MTX, high-dose methotrexate; EI, etoposide, ifosfamide; CEOP, cyclophosphamide, epirubicin, vincristine, prednisone; ECVBP, epirubicin, cyclophosphamide, vindesine, bleomycin, prednisone; PTCL, peripheral T-cell lymphoma; NOS, not otherwise specified; CEEP, cyclophosphamide, epirubicin, vindesine, prednisone; MC, methotrexate, cytarabine; aaIPI, age-adjusted International Prognostic Index; L, low; LI, low intermediate; HI, high intermediate; ITT, intention to treat.
Working Formulation groups are as described in Table 3.
Crossover allowed at relapse, which may account for lack of survival benefit.