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Purpose: Epidemiologic studies show an association between hepatitis C virus (HCV) and B-cell non-Hodgkin's lymphoma (NHL). Treatment and outcome of patients with diffuse large-cell lymphoma (DLCL) and HCV infection are still a matter of debate., Patients and Methods: We studied the HCV-positive patients with B-cell DLCL included in the Groupe d'Etude des Lymphomes de l'Adulte (GELA) programs LNH 93 and LNH 98. They were compared with the other patients with DLCL included in these programs. HCV infection prevalence was 0.5% (26 of 5,586 patients)., Results: Histologic types of HCV-positive DLCL were more frequently transformed from low-grade lymphoma than DLCL in HCV-negative patients (32% v 6%, P = .02). This is also supported by more frequent spleen involvement in HCV-positive patients (46% v 17%, P < .001). HCV-positive patients had more frequently elevated lactate dehydrogenase levels than other patients (77% v 55%, P = .02). Outcome of HCV-positive patients was poorer for overall survival (P = .02) but not for event-free survival (P = .13). After matching on age and prognosis factors, at 2 years of follow-up, the overall survival was 56% (95% CI, 33% to 76%) among HCV-positive patients, versus 80% (70% to 89%), and the event-free survival was 53% (33% to 72%) versus 74% (64% to 84%). The short-term hepatic toxicity of chemotherapy was strongly increased among HCV-positive patients. After exclusion of the two subjects with chronic hepatitis B virus infection, the overall proportion of subjects undergoing hepatic toxicity was 65% (15 of 23 patients)., Conclusion: HCV-positive patients with DLCL differ from other patients both at presentation and during chemotherapy. Specific protocols evaluating antiviral therapy should be designed for these patients.

Purpose: Randomized trial LNH93-3 was conducted on patients who had poor-prognosis aggressive lymphoma and were younger than 60 years with two to three factors of the age-adjusted International Prognostic Index to evaluate the benefit of early high-dose therapy (HDT) with autologous stem-cell transplantation (ASCT)., Patients and Methods: Patients were randomized between doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) chemotherapy followed by sequential consolidation and an experimental shortened treatment consisting of three cycles with escalated doses of cyclophosphamide, epirubicin, vindesine, bleomycin, and prednisone and collection of peripheral-blood stem cells. On day 60, HDT was administered with 1,3-bis(2-chloroethyl)-1-nitrosourea, etoposide, cytarabine, and melphalan followed by ASCT., Results: Eligible patients (n = 370) with aggressive lymphoma were analyzed. For ACVBP (181 patients) and HDT (189 patients), respective complete remission rates were 64% and 63%. With a median follow-up of 60 months, 5-year overall survival and event-free survival for ACVBP and HDT were 60% +/- 8% and 46% +/- 8% (P =.007) and 52 +/- 8% and 39 +/- 8% (P =.01), respectively. Survival was independently affected by age greater than 40 years (P =.0003), T-cell phenotype (P =.009), bone marrow involvement (P =.003), and HDT treatment group (P =.04)., Conclusion: Early HDT with ASCT in high-risk patients was inferior to the ACVBP chemotherapy regimen. These results indicate that the received dose-intensity before HDT was too low when compared with ACVBP and HDT and was given too early.

Purpose: To evaluate prospectively the feasibility and efficacy of early intensive therapy, including intensified cytoreductive chemotherapy (CT) and high-dose CT (HDCT) followed by autologous stem-cell transplantation (ASCT), in patients with advanced Hodgkin's disease (HD) who failed to respond completely or relapsed after initial treatment., Patients and Methods: Among 533 eligible patients with newly diagnosed stage IIIB-IV HD enrolled in the H89 trial, all 157 patients with induction failure (IF) (n = 67), partial response (PR) of less than 75% (n = 22), or relapse (n = 68) were included in this study. Planned salvage therapy included mitoguazone, ifosfamide, vinorelbine, and etoposide monthly for two to three cycles followed by high-dose carmustine, etoposide, cytarabine, and melphalan with ASCT., Results: With a median follow-up of 50 months, the 5-year survival estimates were 30%, 72%, and 76% for the IF, PR, and relapse groups, respectively (P =.0001), 71% for the 101 patients given HDCT, and 32% for the 48 patients treated without HDCT (P =.0001). Multivariate analysis using time-dependent Cox model indicated that B symptoms at progression, salvage without HDCT, and chemoresistant disease before HDCT were significantly associated with shorter overall survival., Conclusion: Early intensive therapy improves the outcomes of patients with advanced HD who failed to respond completely to initial treatment and those who relapsed with adverse prognostic factors. However, for patients with IF and chemoresistant disease, this approach remains unsatisfactory.

Purpose: To present the final analysis, with a median follow-up of 8 years, of the LNH87-2 randomized study, which compares consolidative sequential chemotherapy (ifosfamide plus etoposide, asparaginase, and cytarabine) with high-dose therapy (HDT) using cyclophosphamide, carmustine, and etoposide (CBV regimen) followed by stem-cell transplantation in patients with aggressive non-Hodgkin's lymphoma in first complete remission after induction, focusing on high/intermediate- and high-risk patients identified by the age-adjusted international prognostic index., Patients and Methods: Among the 916 eligible patients, 451 presented with two (n = 318) or three (n = 133) risk factors. After reaching complete remission to induction therapy, 236 of these higher risk patients were assessable for the consolidation phase, with 125 patients in the HDT arm and 111 in the sequential chemotherapy arm., Results: Among these 451 higher risk patients, 277 (61%) achieved complete remission after induction treatment. In the population of 236 randomized patients, HDT was superior to sequential chemotherapy, with 8-year disease-free survival rates of 55% (95% confidence interval [CI], 46% to 64%) and 39% (95% CI, 30% to 48%), respectively (P =.02; relative risk, 1.56). The 8-year survival rate was significantly superior in the HDT arm (64%; 95% CI, 55% to 73%) compared with the sequential chemotherapy arm (49%; 95% CI, 39% to 59%) (P =.04; relative risk, 1.51)., Conclusion: On the basis of the final analysis of this prospectively treated series of patients, retrospectively analyzed on the basis of the International Prognostic Index, we hypothesize that HDT benefits patients at higher risk who achieve complete remission after induction treatment.

Purpose: To compare a short intensified regimen followed by sequential consolidation therapy (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone [ACVBP]) to the standard regimen of methotrexate, bleomycin, cyclophosphamide, and etoposide (m-BACOD) in patients with low-risk aggressive lymphoma., Patients and Methods: A total of 752 patients with intermediate- or high-grade lymphoma and no adverse prognostic factors (Eastern Cooperative Oncology Group performance status of 2 to 4, >/= two extranodal sites of disease, tumor burden >/= 10 cm in largest dimension, bone marrow or CNS involvement, Burkitt's or lymphoblastic subtypes) were registered. Of 673 eligible patients, 332 received ACVBP and 341 received m-BACOD., Results: The complete remission rate was identical (86%) in the two groups. With a median follow-up duration of 7 years, the 5-year failure-free survival (FFS) rate was 65% in the ACVBP group and 61% in the m-BACOD group (P =.16). The 5-year overall survival rate was 75% in the ACVBP group and 73% in the m-BACOD group (P =.47). ACVBP was responsible for more severe and life-threatening infections (P <.01), but m-BACOD caused more pulmonary toxicity (P <.001). The number of treatment-related deaths did not differ between the two regimens. A multivariate analysis indicated that ACVBP was associated with a longer FFS in patients with two or three risk factors of the International Prognostic Index., Conclusion: In this population of patients with low-risk aggressive lymphoma, toxicities of the regimens are different, but the rates of response and survival are identical. The survival advantage of ACVBP over standard regimen in patients with advanced disease is suggested by this analysis but remains to be assessed in prospective studies specifically designed for this purpose.

Purpose: To clarify disease characteristics and optimal treatment for elderly patients with non-Hodgkin's lymphoma (NHL), we performed a randomized trial in 453 patients older than 69 years with aggressive lymphoma., Patients and Methods: Two hundred twenty patients received cyclophosphamide 750 mg/m2, teniposide (VM-26) 75 mg/m2, and prednisone 40 mg/m2/d for 5 days (CVP) and 233 patients received CVP plus pirarubicin (THP-doxorubicin) 50 mg/m2 (CTVP), each for six courses every 3 weeks., Results: The median age was 75 years. Most patients had clinically aggressive disease; 30% had one and 53% two or three adverse prognostic parameters as defined by the International Prognostic Index. More patients on the CTVP arm had an elevated lactic dehydrogenase (LDH) level, but the two groups were otherwise well balanced. CTVP treatment was more frequently associated with leukopenia, thrombocytopenia, and infectious complications. Death during chemotherapy occurred in 16% and 21% of patients on the CVP and CTVP arms, respectively (not significant). Forty percent of patients achieved a complete response (CR): 47% on CTVP and 32% on CVP (chi2 = 20.98, P = .0001). The median time to treatment failure (TTF) was 7 months for CTVP versus 5 months for CVP (log-rank test, P < .05). The median survival time was 13 months in both groups; however, the 5-year survival rate was 26% with CTVP versus 19% with CVP (chi2 = 4.68, P < .05). Lymphoma progression was the primary cause of death., Conclusion: Elderly patients with aggressive lymphoma have an aggressive disease with adverse prognostic parameters at the time of diagnosis. Slightly longer survival was observed for patients treated with an anthracycline-containing regimen.

Purpose: To update the randomized study that compared consolidative sequential treatment (ifosfamide, etoposide, asporaginase, and cytarabine) versus the high-dose regimen of cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation in patients with aggressive non-Hodgkin's lymphoma in first complete remission and to focus on high-intermediate and high-risk patients identified by the international prognostic index., Patients and Methods: Nine hundred sixteen patients received induction treatment on the LNH84 protocol with open randomization for the anthracycline. In a subsequent randomization, 541 patients in complete remission were assigned to receive consolidation by either sequential chemotherapy (n = 273) or autotransplant (n = 268). Among the higher risk population (two or three risk factors), 236 patients in complete remission were assessable for the consolidation phase, with 111 in the sequential chemotherapy arm and 125 in the autotransplant arm., Results: Among 541 randomized patients, disease-free survival and survival did not differ significantly between the two consolidative treatment arms. In the higher risk population, CBV was superior to sequential chemotherapy, with 5-year disease-free survival rates of 59% (95% confidence interval, 49% to 69%) and 39% (95% confidence interval, 28% to 50%), respectively (P = .01, relative risk = 1.19). The 5-year survival rate was superior in the CBV group at 65% (95% confidence interval, 56% to 74%) compared with 52% in the sequential chemotherapy group (95% confidence interval, 42% to 62%) (P = .06, relative risk = 1.49)., Conclusion: This study shows a superior disease-free survival for higher risk patients in complete remission. Dose-intensive consolidation therapy should be considered for patients at higher risk who achieve complete remission after induction treatment.

Purpose: To study the prognostic significance of the small non-cleaved-cell lymphoma (SNCCL) histologic subtype, we compared the outcome of adult patients with SNCCL with that of patients with aggressive lymphoma other than SNCCL by means of two case-controlled studies., Patients and Methods: We analyzed the results of the doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) regimen used as a reference scheme in our cooperative study group (Groupe d'Etude des Lymphomes de l'Adult [GELA]) in 52 adult SNCCL patients with no bone marrow (BM) or CNS involvement. Forty-five SNCCL patients younger than 60 years could be compared with two separate case-matched groups of patients with aggressive lymphoma other than SNCCL undergoing the same therapeutic regimen. In the first case-controlled study, matching ensured identity of each risk factor of the age-adjusted International Index (ie, Ann Arbor stage, performance status, and lactate dehydrogenase [LDH] level); in the second study, matching was performed according to the number of presenting risk factors (zero, one, two, or three), regardless of their nature., Results: The 5-year overall survival rates were not significantly different between SNCCL and control patients in both case-controlled studies: 48% versus 51% in the first study, and 48% versus 55% in the second study., Conclusion: These results support the thesis that in patients with no bone marrow or CNS involvement, the SNCCL histologic subtype does not confer a prognosis worse than that of other aggressive lymphoma.