Rituximab Maintenance for a Maximum of 5 Years After Single-Agent Rituximab Induction in Follicular Lymphoma: Results of the Randomized Controlled Phase III Trial SAKK 35/03.

PURPOSE Rituximab maintenance therapy has been shown to improve progression-free survival in patients with follicular lymphoma; however, the optimal duration of maintenance treatment remains unknown. PATIENTS AND METHODS Two hundred seventy patients with untreated, relapsed, stable, or chemotherapy-resistant follicular lymphoma were treated with four doses of rituximab monotherapy in weekly intervals (375 mg/m(2)). Patients achieving at least a partial response were randomly assigned to receive maintenance therapy with one infusion of rituximab every 2 months, either on a short-term schedule (four administrations) or a long-term schedule (maximum of 5 years or until disease progression or unacceptable toxicity). The primary end point was event-free survival (EFS). Progression-free survival, overall survival (OS), and toxicity were secondary end points. Comparisons between the two arms were performed using the log-rank test for survival end points. RESULTS One hundred sixty-five patients were randomly assigned to the short-term (n = 82) or long-term (n = 83) maintenance arms. Because of the low event rate, the final analysis was performed after 95 events had occurred, which was before the targeted event number of 99 had been reached. At a median follow-up period of 6.4 years, the median EFS was 3.4 years (95% CI, 2.1 to 5.3) in the short-term arm and 5.3 years (95% CI, 3.5 to not available) in the long-term arm (P = .14). Patients in the long-term arm experienced more adverse effects than did those in the short-term arm, with 76% v 50% of patients with at least one adverse event (P < .001), five versus one patient with grade 3 and 4 infections, and three versus zero patients discontinuing treatment because of unacceptable toxicity, respectively. There was no difference in OS between the two groups. CONCLUSION Long-term rituximab maintenance therapy does not improve EFS, which was the primary end point of this trial, or OS, and was associated with increased toxicity.

Enhanced Cold Tolerance in Transgenic Tobacco Expressing a Chloroplast Omega-3 Fatty Acid Desaturase Gene under the Control of a Cold-inducible Promoter

A new cold-inducible genetic construct was cloned using a chloroplast-specific omega-3-fatty acid desaturase gene (FAD7) under the control of a cold-inducible promoter (cor15a) from Arabidopsis thaliana. RT-PCR confirmed a marked increase in FAD7 expression, in young Nicotiana tabacum (cv. Havana) plants harboring cor15a-FAD7, after a short-term exposure to cold. When young, cold-induced tobacco seedlings were exposed to low-temperature (0.5, 2 or 3.5 degrees C) for up to 44 days, survival within independent cor15a-FAD7 transgenic lines (40.2-96%) was far superior to the wild type (6.7-10.2%). In addition, the major trienoic fatty acid species remained stable in cold-induced cor15a-FAD7 N. tabacum plants under prolonged cold storage while the levels of hexadecatrienoic acid (16:3) and octadecatrienoic acid (18:3) declined in wild type plants under the same conditions (79 and 20.7% respectively). Electron microscopy showed that chloroplast membrane ultrastructure in cor15a-FAD7 transgenic plants was unaffected by prolonged exposure to cold temperatures. In contrast, wild type plants experienced a loss of granal stacking and disorganization of the thylakoid membrane under the same conditions. Changes in membrane integrity coincided with a precipitous decline in leaf chlorophyll concentration and low survival rates in wild type plants. Cold-induced double transgenic N. alata (cv. Domino Mix) plants, harboring both the cor15a-FAD7 cold-tolerance gene and a cor15a-IPT dark-tolerance gene, exhibited dramatically higher survival rates (89-90%) than wild type plants (2%) under prolonged cold storage under dark conditions (2 degrees C for 50 days).

Fragm. lat. III 5 - Inventar

Trägerband: Ms. Barth. 129; Vorbesitzer: Bartholomaeusstift Frankfurt am Main

Grain size analysis of sediment core CRP-3 from the Ross Sea, Antarctica

Grain-size analyses by sieve and Sedigraph are presented for 115 samples of core from CRP-3, 12 km off the coast of south Victoria Land. The data provide a useful check on visual core descriptions. The geographic setting for the strata sampled, some 790 m of early Oligocene nearshore marine sediments with a persistent glacial influence, is reviewed, and sediment textures interpreted in that context. Sand textures from the CRP-3 samples in the lower part of the core suggest that deposition was initially primarily wave-dominated, but that at times the influence of the waves was over-ridden by episodes of rapid sedimentation. Sedimentary cycles, recognised in the visual description of the core above 485 mbsf, show an increasing proportion of mudstone in the middle of each cycle above 330 mbsf that is interpreted to record periodic sedimentation in deeper water. Sandstone textures in the lower and upper parts of each cycle are interpreted to record departure from and return to shoreface deposition with changes in sea level. Mudstone textures above 176 mbsf indicate sedimentation below wave base. Many of the textures in both sand and mud samples show the coarse 'tail' characteristic of ice-rafted debris, but others do not, indicating ice-free periods. Many sandstones below c. 200 mbsf have virtually no silt, but significant amounts of clay (6 to 17%) that is thought to be of post-depositional origin.

(Table 3) Sedimentation rates of stage 1 and last glacial maximum from different Holes during cruises of RRS Discovery in 1984-1985 and 1987-1988, and RRS James Clark Ross in 1992-1993

Within the Scotia Sea, the axis of the Antarctic Circumpolar Current (ACC) is geographically confined, and sediments therefore contain a record of palaeo-flow speed uncomplicated by ACC axis migration. We outline Holocene and Last Glacial Maximum (LGM) current-controlled sedimentation using data from 3.5-kHz profiles, cores and current meter moorings. Geophysical surveys show areas of erosion and deposition controlled by Neogene basement topography. Deposition occurs in mounded sediment drifts or flatter areas, where 500-1000 m of sediment overlies acoustic basement. 3.5-kHz profiles show parallel, continuous sub-bottom reflectors with highest sedimentation rates in the centre of the drifts, and reflectors converging towards marginal zones of non-deposition. Locally, on the flanks of continental blocks (e.g. South Georgia), downslope processes are dominant. The absence of mudwaves on the sediment drifts may result from the unsteadiness of ACC flow. A core transect from the ACC axis south to the boundary with the Weddell Gyre shows a southward decrease in biogenic content, controlled by the Polar Front and the spring sea-ice edge. Both these features lay farther north at LGM. The cores have been dated by relative abundance of the radiolarian Cycladophora davisiana, and by changes in the biogenic Ba content, a palaeoproductivity indicator. Sedimentation rates range from 3 to 17 cm/ka. The grain size of Holocene sediments shows a coarsening trend from south to north, consistent with strongest bottom-current flow near the ACC axis, though interpretation is complicated by the presence of biogenic grains. Year-long current meter records indicate mean speeds from 7 cm/s in the south to 12 cm/s in the north, with benthic storm frequency increasing northwards. LGM sediments are predominantly terrigenous and show a clearer northward-coarsening trend, with well-sorted silts in the northern Scotia Sea. Assuming a constant terrigenous source, this implies stronger ACC flow at the LGM, contrasting with weaker Weddell Gyre flow deduced from earlier work.

Table 3: Comparison of freshwater species in Ob and Yenisei during the 1997 cruise

Phytoplankton biomass distribution (chlorophyll a, chl. a) and species composition (cell numbers) were investigated during three expeditions to the Kara Sea with "Akademik Boris Petrov" (BP) in 1997, 1999, and 2000. The distribution of biomass in the estuaries of Ob and Yenisei showed a similar range in 1997 (0.2 to 3.2 µg/l) and 2000 (0.4 to 3.5 ug/l); higher chl. a concentrations during these two years were found in Yenisei than in Ob. In 1999, phytoplankton biomass in the Ob and Ob Estuary was much higher than in 1997 and 2000, with maximum values above 10.0 ug chl. a/l. In 1999, biomass in Yenisei was lower (1.5 to ~5 ug/l) than in Ob but slightly higher than in 1997 and in 2000. During the expedition in 2000, the research area extended farther to the north, here, lowest phytoplankton biomass during all three years was found. Typical summer values for integrated chl.a biomass (surface to bottom) ranged between 6 and 20 mg m**-2. Strong differences existed in species composition in both rivers, the estuaries, and the open Kara Sea. In general, three or four different populations could be distinguished in surface waters: (1) freshwater diatoms together with bluegreen algae in both rivers, (2) centric and small pennate diatoms mainly brackish species in the estuaries, (3) north of 74°N, brackish/marine species dominated, i.e. in 1999 Thalassiosira cfpunctigera and Chaetoceros spp prevailed in the phytoplankton bloom in Ob. (4) At the northernmost, almost marine stations, a region with a more heterogeneous composition of unicellular plankton was encountered. We assume, we found different seasonal signals of phytoplankton development during 1997/2000 and 1999, respectively. However, the yearly fluctuation of freshwater runoff of both rivers seems to have the strongest influence on the timing and duration of phytoplankton blooms, species compositions and biomass standing stocks during summer.