| 21. |
- Schmid, C, et al.
(författare)
-
Long-term results and GvHD after prophylactic and preemptive donor lymphocyte infusion after allogeneic stem cell transplantation for acute leukemia
- 2022
-
Ingår i: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 57:2, s. 215-223
-
Tidskriftsartikel (refereegranskat)abstract
- We report on 318 patients with acute leukemia, receiving donor lymphocyte infusion (DLI) in complete hematologic remission (CHR) after allogeneic stem cell transplantation (alloSCT). DLI were applied preemptively (preDLI) for minimal residual disease (MRD, n = 23) or mixed chimerism (MC, n = 169), or as prophylaxis in high-risk patients with complete chimerism and molecular remission (proDLI, n = 126). Median interval from alloSCT to DLI1 was 176 days, median follow-up was 7.0 years. Five-year cumulative relapse incidence (CRI), non-relapse mortality (NRM), leukemia-free and overall survival (LFS/OS) of the entire cohort were 29.1%, 12.7%, 58.2%, and 64.3%. Cumulative incidences of acute graft-versus-host disease (aGvHD) grade II–IV°/chronic GvHD were 11.9%/31%. Nineteen patients (6%) died from DLI-induced GvHD. Age ≥60 years (p = 0.046), advanced stage at transplantation (p = 0.003), shorter interval from transplantation (p = 0.018), and prior aGvHD ≥II° (p = 0.036) were risk factors for DLI-induced GvHD. GvHD did not influence CRI, but was associated with NRM and lower LFS/OS. Efficacy of preDLI was demonstrated by decreasing MRD/increasing blood counts in 71%, and increasing chimerism in 70%. Five-year OS after preDLI for MRD/MC was 51%/68% among responders, and 37% among non-responders. The study describes response and outcome of DLI in CHR and helps to identify candidates without increased risk of severe GvHD.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
- Ciarelli, Giancarlo, et al.
(författare)
-
Trends of inorganic and organic aerosols and precursor gases in Europe: Insights from the EURODELTA multi-model experiment over the 1990-2010 period
- 2019
-
Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 12:12, s. 4923-4954
-
Tidskriftsartikel (refereegranskat)abstract
- In the framework of the EURODELTA-Trends (EDT) modeling experiment, several chemical transport models (CTMs) were applied for the 1990-2010 period to investigate air quality changes in Europe as well as the capability of the models to reproduce observed long-term air quality trends. Five CTMs have provided modeled air quality data for 21 continuous years in Europe using emission scenarios prepared by the International Institute for Applied Systems Analysis/Greenhouse Gas - Air Pollution Interactions and Synergies (IIASA/GAINS) and corresponding year-by-year meteorology derived from ERA-Interim global reanalysis. For this study, long-term observations of particle sulfate (SO2 4-), total nitrate (TNO3), total ammonium (TNHx) as well as sulfur dioxide (SO2) and nitrogen dioxide (NO2) for multiple sites in Europe were used to evaluate the model results. The trend analysis was performed for the full 21 years (referred to as PT) but also for two 11-year subperiods: 1990-2000 (referred to as P1) and 2000-2010 (referred to as P2). The experiment revealed that the models were able to reproduce the faster decline in observed SO2 concentrations during the first decade, i.e., 1990-2000, with a 64%-76% mean relative reduction in SO2 concentrations indicated by the EDT experiment (range of all the models) versus an 82% mean relative reduction in observed concentrations. During the second decade (P2), the models estimated a mean relative reduction in SO2 concentrations of about 34%-54%, which was also in line with that observed (47%). Comparisons of observed and modeled NO2 trends revealed a mean relative decrease of 25% and between 19% and 23% (range of all the models) during the P1 period, and 12% and between 22% and 26% (range of all the models) during the P2 period, respectively. Comparisons of observed and modeled trends in SO4 2- concentrations during the P1 period indicated that the models were able to reproduce the observed trends at most of the sites, with a 42%-54% mean relative reduction indicated by the EDT experiment (range of all models) versus a 57% mean relative reduction in observed concentrations and with good performance also during the P2 and PT periods, even though all the models overpredicted the number of statistically significant decreasing trends during the P2 period. Moreover, especially during the P1 period, both modeled and observational data indicated smaller reductions in SO42- concentrations compared with their gas-phase precursor (i.e., SO2), which could be mainly attributed to increased oxidant levels and pH-dependent cloud chemistry. An analysis of the trends in TNO3 concentrations indicated a 28%-39% and 29% mean relative reduction in TNO3 concentrations for the full period for model data (range of all the models) and observations, respectively. Further analysis of the trends in modeled HNO3 and particle nitrate (NO-3 ) concentrations revealed that the relative reduction in HNO3 was larger than that for NO-3 during the P1 period, which was mainly attributed to an increased availability of "free ammonia". By contrast, trends in modeled HNO3 and NO-3 concentrations were more comparable during the P2 period. Also, trends of TNHx concentrations were, in general, underpredicted by all models, with worse performance for the P1 period than for P2. Trends in modeled anthropogenic and biogenic secondary organic aerosol (ASOA and BSOA) concentrations together with the trends in available emissions of biogenic volatile organic compounds (BVOCs) were also investigated. A strong decrease in ASOA was indicated by all the models, following the reduction in anthropogenic non-methane VOC (NMVOC) precursors. Biogenic emission data provided by the modeling teams indicated a few areas with statistically significant increase in isoprene emissions and monoterpene emissions during the 1990-2010 period over Fennoscandia and eastern European regions (i.e., around 14 %-27 %), which was mainly attributed to the increase of surface temperature. However, the modeled BSOA concentrations did not linearly follow the increase in biogenic emissions. Finally, a comprehensive evaluation against positive matrix factorization (PMF) data, available during the second period (P2) at various European sites, revealed a systematic underestimation of the modeled SOA fractions of a factor of 3 to 11, on average, most likely because of missing SOA precursors and formation pathways, with reduced biases for the models that accounted for chemical aging of semi-volatile SOA components in the atmosphere.
|
|
| 27. |
|
|
| 28. |
- Dorfmeister, B, et al.
(författare)
-
Effects of six APOA5 variants, identified in patients with severe hypertriglyceridemia, on in vitro lipoprotein lipase activity and receptor binding
- 2008
-
Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 28:10, s. 1866-1871
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The purpose of this study was to identify rare APOA5 variants in 130 severe hypertriglyceridemic patients by sequencing, and to test their functionality, since no patient recall was possible. METHODS AND RESULTS: We studied the impact in vitro on LPL activity and receptor binding of 3 novel heterozygous variants, apoAV-E255G, -G271C, and -H321L, together with the previously reported -G185C, -Q139X, -Q148X, and a novel construct -Delta139 to 147. Using VLDL as a TG-source, compared to wild type, apoAV-G255, -L321 and -C185 showed reduced LPL activation (-25% [P=0.005], -36% [P<0.0001], and -23% [P=0.02]), respectively). ApoAV-C271, -X139, -X148, and Delta139 to 147 had little affect on LPL activity, but apoAV-X139, -X148, and -C271 showed no binding to LDL-family receptors, LR8 or LRP1. Although the G271C proband carried no LPL and APOC2 mutations, the H321L carrier was heterozygous for LPL P207L. The E255G carrier was homozygous for LPL W86G, yet only experienced severe hypertriglyceridemia when pregnant. CONCLUSIONS: The in vitro determined function of these apoAV variants only partly explains the high TG levels seen in carriers. Their occurrence in the homozygous state, coinheritance of LPL variants or common APOA5 TG-raising variant in trans, appears to be essential for their phenotypic expression.
|
|
| 29. |
- Hayden, PJ, et al.
(författare)
-
Second allogeneic transplants for multiple myeloma: a report from the EBMT Chronic Malignancies Working Party
- 2021
-
Ingår i: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 56:10, s. 2367-2381
-
Tidskriftsartikel (refereegranskat)abstract
- The EBMT Chronic Malignancies Working Party performed a retrospective analysis of 215 patients who underwent a second allo-HCT for myeloma between 1994 and 2017, 159 for relapse and 56 for graft failure. In the relapse group, overall survival (OS) was 38% (30–46%) at 2 years and 25% (17–32%) at 5 years. Patients who had a HLA-identical sibling (HLAid-Sib) donor for their first and second transplants had superior OS (5 year OS: HLAid-Sib/HLAid-Sib: 35% (24–46%); Others 9% (0–17%), p < 0.001). There was a significantly higher incidence of acute grade II-IV GvHD in those patients who had also developed GvHD following their initial HLA-identical sibling allo-HCT (HLAid-Sib/HLAid-Sib: 50% (33–67%); Other 22% (8–36%), p = 0.03). More as opposed to fewer than 2 years between transplants was associated with superior 5-yr OS (31% (21–40%) vs. 10% (1–20%), P = 0.005). On multivariate analysis, consecutive HLA-identical sibling donor transplants conferred a significant OS advantage (0.4 (0.24–0.67), p < 0.001). In the graft failure group, OS was 41% at 2 years. In summary, a second allo-HCT using a HLA-identical sibling donor, if available, provides the best transplant outcomes for relapsed myeloma in this setting.
|
|
| 30. |
|
|
