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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 wets superior to sequential chemotherapy, with I-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. (C) 2000 by American Society of Clinical Oncology.

Purpose: To compare ct 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, greater than or equal to two extranodal sites of disease, tumor burden greater than or equal to 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 wets identical (86%) in the two groups. With a median follow-up duration of 7 years, the 5-year failure-free survival (FFS) rate wets 65% in the ACVBP group and 61% in the m-BACOD group (P = .16), The 5-year overall survival rate wets 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 wets 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. (C) 2000 by American Society of Clinical Oncology

Background: Incidence of central nervous system (CNS) recurrence in patients with aggressive non-Hodgkin's lymphoma who did not receive meningeal prophylaxis is about 5%. Controversy remains regarding risk factors associated with such an event preventing a rational approach of prophylactic strategies. Patients and methods: We analyzed a cohort of 974 patients with aggressive lymphoma in complete remission (CR). All the patients received a CNS prophylaxis consisting of intrathecal injections and intravenous high-dose methotrexate. The risk repartition on the basis of the international prognostic index (IPI) of these 974 CR-patients was low (L): 41%, low-intermediate (LI): 27%, high-intermediate (HI): 19%, high (H): 13%. Results: The incidence of isolated CNS relapse was 1.6%. In a first multivariate logistic regression analysis an increased LDH (P= 0.05, RR = 5) and the presence of more than one extranodal site (P= 0.05, RR = 3) were identified as independent risk factors for isolated CNS relapse. Another multivariate analysis incorporating IPI as a unique parameter showed that only IPI remained significantly associated with a higher risk of CNS relapse (L-LI: 0.6% vs. HI-H: 4.1%, P = 0.002; RR = 7). Conclusion: Prophylaxis notably reduces the risk of CNS recurrence in the higher risk patients. By contrast, we propose the deletion of prophylactic intrathecal injections in the lower risk patients.

Purpose: To update the randomized study that compared consolidative sequential treatment (ifosfamide, etoposide, asparaginase, 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. (C) 1997 by American Society of Clinical Oncology.