First-line high-dose therapy and autologous blood stem cell transplantation in patients with primary central nervous system non-Hodgkin lymphomas-a single-centre experience in 61 patients

Primary central nervous system non-Hodgkin lymphomas (PCNS-NHLs) are extranodal B-cell lymphomas with poor prognosis. The role of high-dose therapy (HDT) followed by autologous blood stem cell transplantation (ASCT) as first-line therapy is still not clear. We retrospectively collected long-term follow up data of 61 consecutive patients with PCNS-NHL at the University Hospital Düsseldorf from January 2004 to December 2016. Thirty-six patients were treated with conventional chemoimmunotherapy (cCIT) only (CT-group). Seventeen patients received an induction cCIT followed by HDT and ASCT. In the CT-group, the overall response rate (ORR) was 61% (CR 47%, PR 14%), and there were 8% treatment-related deaths (TRD). Progression-free survival (PFS) was 31.8 months, and overall survival (OS) was 57.3 months. In the HDT-group, the ORR was 88% (59% CR, 29% PR), and there were 6% TRD. Median PFS and OS were not reached at 5 years. The 5-year PFS and OS were 64.7%. After a median follow up of 71 months, 10 patients (59%) were still alive in CR/PR following HDT and ASCT, one patient was treated for progressive disease (PD), and 7 had died (41%, 6 PD, 1 TRD). All patients achieving CR prior to HDT achieved durable CR. In the CT-group, 8 patients (22%) were alive in CR/PR after a median follow-up of 100 months. Twenty-eight patients died (78%, 24 PD, 2 TRD, 2 deaths in remission). In the univariate analysis, the HDT-group patients had significantly better PFS (not reached vs 31.8 months, p = 0.004) and OS (not reached vs 57.3 months, p = 0.021). The multivariate analysis showed HDT was not predictive for survival. Treatment with HDT + ASCT is feasible and offers the chance for long-term survival with low treatment-related mortality in younger patients. In this analysis, ORR, PFS and OS were better with HDT than with conventional cCIT alone. This result was not confirmed in the multivariate analysis, and further studies need to be done to examine the role of HDT in PCNSL

Oxygen minimum zone induced rapid temporal fluctuations of Eastern Baltic cod genetic diversity

Oxygen minimum zones are increasing, yet the effects of these zones on the genetic composition of marine fish stocks has been neglected. We assessed the combined effects of stock size and structure, and the prevailing oxygen situation, on Eastern Baltic cod (ICES SD25) genetic diversity. For this purpose, we used an integrative long-term otolith sample and data series (1995-2013) to (1) calculate the approximate number of females with surviving eggs in a given year, i.e., contributing to reproduction (n F), and (2) the annually resolved cohort mean allelic richness as proxy of genetic diversity, based on 12 microsatellite markers. Cohort mean allelic richness showed strong year-to-year fluctuations though no permanent decline. Importantly, it was highly correlated with n F, but with an unexpected 1.5 year time lag that may be an artefact of Eastern Baltic cod ageing problems. Our findings indicated that environmental pressure can effect rapid alterations in exploited fish stock genetic composition, and pointed to the importance of large females for Eastern Baltic cod reproduction during stagnation periods. Considering the importance of standing genetic variation for the evolutionary potential of populations, this is relevant for projections of the future state of cod stocks under global change

Potential and limitations of ozone for the removal of ammonia, nitrite, and yellow substances in marine recirculating aquaculture systems

The high levels of water-reuse in intensive recirculating aquaculture systems (RAS) require an effective water treatment in order to maintain good water quality. In order to reveal the potential and limitations of ozonation for water quality improvement in marine RAS, we tested ozone's ability to remove nitrite, ammonia, yellow substances and total bacterial biomass in seawater, considering aspects such as efficiency, pH-dependency as well as the formation of toxic ozone-produced oxidants (OPO). Our results demonstrate that ozone can be efficiently utilized to simultaneously remove nitrite and yellow substances from process water in RAS without risking the formation of toxic OPO concentrations. Contemporaneously, an effective reduction of bacterial biomass was achieved by ozonation in combination with foam fractionation. In contrast, ammonia is not oxidized by ozone so long as nitrite and yellow substances are present in the water, as the dominant reaction of the ozone-based ammonia-oxidation in seawater requires the previous formation of OPO as intermediates. The oxidation of ammonia in seawater by ozone is basically a bromide-catalyzed reaction with nitrogen gas as end product, enabling an almost complete removal of ammonia-nitrogen from the aquaculture system. Results further show that pH has no effect on the ozone-based ammonia oxidation in seawater. Unlike in freshwater, an effective removal of ammonia even at pH-values as low as 6.5 has been shown to be feasible in seawater. However, as the predominant reaction pathway involves an initial accumulation of OPO to toxic amounts, we consider the ozone-based removal of ammonia in marine RAS as risky for animal health and economically unviable