PURPOSE:This trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group compares the use of high-dose therapy (HDT) as part of primary treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus etoposide followed by involved-field (IF) radiotherapy in a randomized, multicenter, phase III study.PATIENTS AND METHODS:Three hundred twelve patients with "aggressive" non-Hodgkin's lymphoma aged <or= 60 years with elevated serum lactate dehydrogenase levels were included from 1990 to 1997. Patients with at least a minor response after two cycles of CHOEP (CHOP + etoposide 3 x 100 mg/m(2)) were to receive three further cycles of CHOEP followed by IF radiotherapy (arm A) or one further cycle of CHOEP followed by autologous stem-cell transplantation and IF radiotherapy (arm B).RESULTS:Among 158 patients randomized to arm B, 103 (65%) received HDT. The complete remission rate at the end of treatment was 62.9% in arm A and 69.9% in arm B. With a median observation time of 45.5 months, overall survival for all 312 patients was 63% after 3 years (63% for arm A, 62% for arm B; P =.68). Event-free survival was 49% for arm A versus 59% for arm B (P =.22). Relapse in arm B was associated with a significantly worse survival rate than relapse in arm A (P <.05). Relapse after HDT occurred early (median interval, 3 months). Six patients developed secondary neoplasia, three in arm A and three in arm B.CONCLUSION:Results of the randomized trial comparing CHOP-like chemotherapy with early HDT do not support the use of HDT with carmustine, etoposide, cytarabine, and melphalan following shortened standard chemotherapy.

BACKGROUND:With CHOP, the standard protocol of recent decades, about 30% of long-term survival has been reported. A number of studies using more aggressive multidrug regimens or alternating chemotherapies have recently suggested higher CR rates and increased survival. In 1989 we reported similar results with a combined-modality treatment administering 6 cycles of CHOP supplemented with etoposide and an involved field irradiation for patients in PR or CR. PATIENTS AND METHODS:To confirm the efficacy of this approach, we initiated a prospective randomised trial comparing 4 cycles of CHOP-VP16 (CHOEP) with 4 cycles of two alternating regimens, 'hCHOP and IVEP'. One hundred seventy-five patients with high-grade non-Hodgkin's lymphomas stages II-IV were stratified for age, stage and LDH and randomised to receive either four cycles of cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone (CHOEP) in arm A or four cycles of chemotherapy with a dose-intensified CHOP (hCHOP) alternating with ifosfamide, etoposide, vindesine, prednisolone (IVEP) in arm B. After four cycles of chemotherapy an involved field irradiation with a total dose of 35 Gy was given to all patients demonstrated to be in complete or partial remission. RESULTS:Of the 185 randomised patients, 175 were eligible and 171 evaluable for response and survival. One hundred forty-six of the 171 patients (85%) achieved complete remission (CR) with 87% and 84% CRs in arms A and B, respectively. With a median follow-up of 36 months the estimated overall survival at 2 years is 66% and 73% for arms A and B, respectively. The percentage of all patients in first CR is estimated to be 59% and 55% at 2 years for arms A and B, respectively. None of the differences in CR rate, survival, or relapse-free survival are statistically significant. Multivariate analysis of subgroups incorporating the factors of sex, age, performance status, stage, B symptoms, bulky disease, LDH and histology revealed that only stage and LDH were factors which independently affected outcome. The estimated 2-year survival rate of patients with stages II, III and IV is predicted to be 84%, 62% and 52%, respectively. Patients with LDH > 250 U/l have an estimated survival of 52% at 2 years versus 84% for patients with LDH < or = 250 U/l. According to the newly proposed international score system, the 2-year survival was 81% for low-risk-, 64% for low intermediate risk-, 50% for high intermediate risk-, and 43% for high-risk patients. The toxicity in both arms was tolerable. Three patients died of treatment-related causes (2 in arm A, 1 in arm B). The main toxicity was haematological with 75% of patients suffering from grades 3 or 4 neutropenia at some point during treatment. CONCLUSIONS:We observed no superior benefit for alternating regimens, and conclude that both are effective treatment protocols for aggressive histologic-type malignant lymphomas. The results obtained with four cycles of poly-chemotherapy followed by an involved field irradiation are comparable to programs using more aggressive and/or prolonged chemotherapy.

185 patients with high grade non-Hodgkin's lymphoma stages II-IV entered this multicentre trial and were randomized to receive either four cycles of CHOEP (cyclophosphamide 750 mg/m2 i.v. d 1, doxorubicin 50 mg/m2 i.v. d 1, vincristine 2 mg i.v. d 1, etoposide 100 mg/m2 i.v. d 3-5, prednisolone 100 mg p.o. d 1-5) (treatment arm A), or four cycles of chemotherapy with hCHOP (cyclophosphamide 1,200 mg/m2 i.v. d 1, doxorubicin 40 mg/m2 i.v. d 1 + 2, vincristine 2 mg i.v. d 1, prednisolone 100 mg p.o. d 1-5) alternating with IVEP (ifosfamide 1,500 mg/m2 i.v. d 1-5, vindesine 3 mg/m2 i.v. d 1, etoposide 120 mg/m2 i.v. d 3-5, prednisolone 100 mg p.o. d 1-5) in treatment arm B. After four cycles of chemotherapy an involved field irradiation with a total dose of 35 Gy was given to all patients demonstrated to be in complete or partial remission without persisting extranodal disease.So far, 146 patients have completed treatment and are evaluable for response and survival. A complete response (CR) was seen in 124/146 patients (86%) with 89% CR in arm A vs. 83% CR in arm B. During a median follow-up of 17 months (range 2-40) 30 patients relapsed (16 pts. arm A, 14 pts. arm B). The overall survival at 40 months is projected to be 70% vs. 71% for arm A and B, respectively. Disease-free survival is projected to be 68% in arm A and 59% in arm B at 40 months. So far, the differences in CR, survival and disease-free survival are not statistically significant. Toxicity of all regimens was acceptable, however, with a significant morbidity and one treatment-related death in patients > 70 years after hCHOP. Main side effects were mild nausea/vomiting, leukopenia and fever/infection associated with leukopenia.In conclusion, both treatment modalities produced high complete remission rates. A longer follow-up will be needed to exclude differences in overall and disease-free survival.

In a multicentre phase III trial 105 previously untreated patients with high-grade non-Hodgkin's lymphomas stage II-IV were randomized to receive either 4 cycles of CHOEP (cyclophosphamide 750 mg/m2 i.v. day 1, doxorubicin 50 mg/m2 i.v. day 1, vincristine 2 mg i.v. day 1, etoposide 100 mg/m2 i.v. days 3-5, prednisolone 100 mg p.o. days 1-5) (treatment arm A), or 4 cycles of chemotherapy with hCHOP (cyclophosphamide 1,200 mg/m2 i.v. day 1, doxorubicin 40 mg/m2 i.v. days 1 + 2, vincristine 2 mg i.v. day 1, prednisolone 100 mg p.o. days 1-5) alternating with IVEP (ifosfamide 1,500 mg/m2 i.v. days 1-5, vindesine 3 mg/m2 i.v. day 1, etoposide 120 mg/m2 i.v. days 3-5, prednisolone 100 mg p.o. days 1-5) in treatment arm B. After 4 cycles of chemotherapy an involved field irradiation with a total dose of 35 Gy was given to all patients demonstrated to be in complete or partial remission without persisting extranodal disease. A complete response (CR) was seen in 86/105 patients (82%) with 88% CR in arm A vs. 76% CR in arm B. During a median follow-up of 11 months (range 2-31 months) 13 patients relapsed (6 patients arm A, 7 patients arm B). The overall survival at 30 months is projected to be 72% vs. 83% for arm A and B respectively. Disease-free survival is projected to be 78% in arm A and 45% in arm B at 28 months. So far, the differences in CR, survival and disease-free survival are not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Der hier vorliegende Band ist die Dokumentation einer Tagung, die im Oktober 2013 im Archiv der deutschen Jugendbewegung auf Burg Ludwigstein stattfand (siehe die Tagungsankundigung unter [http://www.hsozkult.de/event/id/termine-22612]). Er bietet zum einen Impressionen uber die Landschaft der freien Archive zu den Jugendund den (neuen) sozialen Bewegungen und enthalt zum anderen einige Denkanstose uber deren Situation und Perspektiven. Den Rahmen bilden die – vollig unterschiedlichen – Situationen dieser Archive, dann die Debatte darum, welchen Wert welche Quellen haben und drittens die Zukunft des Archivs auf Ludwigstein selbst. Die dem heterogenen Feld entsprechenden, sehr unterschiedlichen, insgesamt neun Beitrage stellen einzelne Archive und ihre Selbstverortung vor (Archiv des Hamburger Instituts fur Sozialforschung, Archiv der Jugendkulturen, Berlin) oder skizzieren anhand zweier konkreter Forschungsbeispiele – Krautrock beziehungsweise Jugendzentrumsbewegung – die vorgefundene Uberlieferungssituation. MitarbeiterInnen der Stadtarchive Hannover und Gottingen erzahlen schlieslich davon, welche und wie viele Dokumente aus Protestbewegungen sie jeweils verwahren. Jurgen Bacia und Cornelia Wenzel geben anhand ihrer im Buch Bewegung bewahren. Freie Archive und die Geschichte von unten (Berlin 2013) dokumentierten Ergebnisse einen Uberblick uber die, wie sie es nennen, „freien Archive“ zu den und der neuen sozialen Bewegungen. Michael Koltan, langjahriger Mitarbeiter des Archivs der sozialen Bewegungen in Baden (Freiburg) fragt schlieslich mehr als

Das TNM Project Committee der UICC und das DSK