| 1. |
- Joffrin, E., et al.
(författare)
-
Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
-
Forskningsöversikt (refereegranskat)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Modvig, S, et al.
(författare)
-
Value of Flow Cytometry for MRD-Based Relapse Prediction in B-Cell Precursor Acute Lymphoblastic Leukemia in a Multi-Center Setting
- 2019
-
Ingår i: Blood. - 0006-4971 .- 1528-0020.
-
Konferensbidrag (refereegranskat)abstract
- Background: PCR of rearranged antigen receptor genes is the method of choice for MRD quantification in ALL. Although FCM-MRD is faster and biologically more informative than PCR, the analysis requires a high level of training. The only larger published studies using FCM-MRD based stratification (Borowitz, Blood, 2008 and 2015) showed a clear association with clinical outcome in BCP-ALL. However, MRD analyses were centralized and these studies included only one MRD-based stratification (MRD levels at the end of induction). Patients and methods: We examined FCM-MRD as stratification tool in BCP-ALL at various timepoints in a large-scale multicenter (18 MRD centers) study. A total of 1487 patients with BCP-ALL (1298 children (younger than 18 years) and 189 adults (18-45 years) are included in the study and were treated according to the NOPHO ALL2008 protocol between July 2008 and February 2016. The median follow-up time for patients in first remission was 51 months (IQR 32-75). MRD was measured by FCM and/or real time quantitative PCR on days 15, 29 (end of induction) and 79 (for standard (SR) and intermediate risk (IR) patients) and prior to and after high risk blocks. A 6-colour FCM analysis including 3 standardized antibody combinations was used and performed in 18 laboratories. Patients were stratified by FCM-MRD, or by PCR-MRD if no FCM-MRD marker was available. End-of-induction MRD (cut-off 10-3) was used to stratify patients to standard risk (SR) vs intermediate risk (IR) or IR vs high risk consolidation therapy (in case of WBC > 100 x 109/L at diagnosis). Patients with MRD >=2.5x10-1 on day 15 were stratified to high risk block therapy. Patients with MRD >=5x10-2 on day 29 or day 79/post high risk-2 block MRD >=10-3 were stratified to HSCT. Primary outcomes were 5year event-free survival (5y EFS) and 5year cumulative incidence of relapse (5y CIR). Results: Only two patients (0.14% of total) had neither an informative FCM nor a PCR marker, and an informative FCM marker combination for MRD monitoring was identified in 96.2% of patients. There was a significant correlation between FCM- and PCR-MRD levels on day 15 (r=0.77, p<0.0001, n=153) and 29 (r=0.81, p<0.0001, n=140). Based on FCM-MRD only, the median MRD level on day 15, 29 and 79/post high risk-2 block was 5x10-3, 1.1x10-4, and below detection limit, respectively. Adults had significantly higher MRD levels at all time-points (p<0.0001 for day 15 and 29, p=0.0019 for day 79, Mann-Whitney). The 5y EFS was 86.1% (95% CI 84.1-88.1) with a 5y CIR of 9.5% (95% CI 7.8-11.3, n=1487). The day 29 FCM-MRD level was closely associated with clinical outcome and a higher hazard of relapse was seen independently for a FCM-MRD >=10-3 (hazard ratio (HR) 2.4, CI 1.6-3.7, p<0.0001), age>18 year (HR 3.0, CI 1.7-5.3, p<0.0001), WBC>=100 (HR 2.7, CI 1.6-4.6, p=0.0001), and B-other (HR 2.1, CI 1.2-3.5, p=0.0052) or high risk B-ALL cytogenetic aberration (rearranged KMT2A/iAMPchr21/hypodiploid) (HR 3.2, CI 1.6-6.1, p=0.0006) (multivariate cause-specific Cox regression, n=1328). Patients with a day 79 FCM-MRD >=10-4 and <10-3 had a significantly higher CIR (22.1%, CI 10.8-33.5%, n=68) compared to FCM-MRD <10-4 (7.5%, CI 2.1-12.8%, n=110) or undetectable (6.3%, CI 4.5-8.2%, n=999, p=0.0087 for FCM-MRD >=10-4 and <10-3vs <10-4 or undetectable). After adjusting for WBC, age, and the day 29 FCM-MRD level, a day 79 FCM-MRD >=10-4 and <10-3 was still significantly associated with a worse 5y CIR for non-transplanted patients (HR 2.3, CI 1.19-4.36, p=0.012 compared to undetectable FCM-MRD, n=1171). Patients with day 15 FCM-MRD <10-3 had a significantly better 5y EFS (92.0%, CI 89.2-95.0%) and CIR (3.9%, CI 1.7-6.1%, n=432) than patients with FCM-MRD >=10-3 and <2.5x10-1, who had a 5y EFS of 85.5% (CI 82.7-88.3%, p=0.0016, n=837) and a 3-fold higher 5y CIR (11.0%, CI 8.4-13.5%, p<0.0001, n=432). Among patients with day 15 FCM-MRD<10-3, the relapse incidence was comparable for patients with FCM-MRD 10-4 - <10-3 and below 10-4 (CIR 3.6, CI 0.5-6.7 vs. CIR 4.1, CI 1.0-7.2, p=0.83, n=432). Conclusion: FCM-MRD performed in a multi-center setting is a clinically useful method for disease monitoring and MRD-based treatment stratification in BCP-ALL. Moreover, FCM-MRD is a reliable indicator of outcome in BCP-ALL independently of other key risk factors. Residual disease >=10-4 and <10-3 at day 79 in SR/IR patients not allocated to HSCT further identifies patients with a high risk of relapse.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
