ALBERT

Description: Intraplate processes, such as continental surface uplift and intraplate volcanism, are enigmatic and the underlying mechanisms responsible are not fully understood. Central Mongolia is an ideal natural laboratory for studying such processes because of its location in the continental interior far from tectonic plate boundaries, its high-elevation plateau, and its widespread, low-volume, basaltic volcanism. The processes responsible for developing this region remain largely unexplained — due in part to a lack of high-resolution geophysical studies — and thus are open questions. A recent project undertaken to map the crust and upper mantle structure of central Mongolia has collected a large magnetotelluric array (~700 km x ~450 km).

Description: Crustal architecture strongly influences the development and emplacement of mineral zones. In this study, we image the crustal structure beneath a metallogenic belt and its surroundings in the Bayankhongor area of central Mongolia. In this region, an ophiolite belt marks the location of an ancient suture zone, which is presently associated with a reactivated fault system. Nearby, metamorphic and volcanic belts host important mineralization zones and constitute a significant metallogenic belt that includes sources of copper and gold. However, the crustal structure of these features, and their relationships, are poorly studied. We analyze magnetotelluric data acquired across this region and generate three-dimensional electrical resistivity models of the crustal structure, which is found to be locally highly heterogeneous. Because the upper crust (〈 25 km) is found to be generally highly resistive (〉 1000 Ωm), low-resistivity (〈 50 Ωm) features are conspicuous. Anomalous low-resistivity zones are congruent with the suture zone, and ophiolite belt, which is revealed to be a major crustal-scale feature. Furthermore, broadening low-resistivity zones located down-dip from the suture zone suggest that the narrow deformation zone observed at the surface transforms to a wide area in the deeper crust. Other low-resistivity anomalies are spatially associated with the surface expressions of known mineralization zones; thus, their links to deeper crustal structures are imaged. Considering the available evidence, we determine that, in both cases, the low resistivity can be explained by hydrothermal alteration along fossil fluid pathways. This illustrates the pivotal role that crustal fluids play in diverse geological processes, and highlights their inherent link in a unified system, which has implications for models of mineral genesis and emplacement. The results demonstrate that the crustal architecture—including the major crustal boundary—acts as a first‐order control on the location of the metallogenic belt.

Description: Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659

Description: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung http://dx.doi.org/10.13039/501100001711

Description: Westfälische Wilhelms-Universität Münster (1056)

Description: SUMMARY We present a novel frequency-domain inverse solution to recover the 3-D electrical conductivity distribution in the mantle. The solution is based on analysis of local C -responses. It exploits an iterative gradient-type method—limited-memory quasi-Newton method—for minimizing the penalty function consisting of data misfit and regularization terms. The integral equation code is used as a forward engine to calculate responses and data misfit gradients during inversion. An adjoint approach is implemented to compute misfit gradients efficiently. Further improvements in computational load come from parallelizing the scheme with respect to frequencies, and from setting the most time-consuming part of the forward calculations—calculation of Green’s tensors—apart from the inversion loop. Convergence, performance, and accuracy of our 3-D inverse solution are demonstrated with a synthetic numerical example. A companion paper applies the strategy set forth here to real data.

Description: SUMMARY We present a novel frequency-domain inverse solution to recover the 3-D electrical conductivity distribution in the mantle. The solution is based on analysis of local C -responses. It exploits an iterative gradient-type method—limited-memory quasi-Newton method—for minimizing the penalty function consisting of data misfit and regularization terms. The integral equation code is used as a forward engine to calculate responses and data misfit gradients during inversion. An adjoint approach is implemented to compute misfit gradients efficiently. Further improvements in computational load come from parallelizing the scheme with respect to frequencies, and from setting the most time-consuming part of the forward calculations—calculation of Green’s tensors—apart from the inversion loop. Convergence, performance, and accuracy of our 3-D inverse solution are demonstrated with a synthetic numerical example. A companion paper applies the strategy set forth here to real data.

Description: Magnetotelluric (MT), radiomagnetotelluric (RMT), and, in particular, controlled-source audiomagnetotelluric (CSAMT) data are often heavily distorted by near-surface inhomogeneities. We developed a novel scheme to invert MT, RMT, and CSAMT data in the form of scalar or tensorial impedances and vertical magnetic transfer functions simultaneously for layer resistivities and electric and magnetic galvanic distortion parameters. The inversion scheme uses smoothness constraints to regularize layer resistivities and either Marquardt-Levenberg damping or the minimum-solution length criterion to regularize distortion parameters. A depth of investigation range is estimated by comparing layered model sections derived from first- and second-order smoothness constraints. Synthetic examples demonstrate that earth models are reconstructed properly for distorted and undistorted tensorial CSAMT data. In the inversion of scalar CSAMT data, such as the determinant impedance or individual tensor elements, the reduced number of transfer functions inevitably leads to increased ambiguity for distortion parameters. As a consequence of this ambiguity for scalar data, distortion parameters often grow over the iterations to unrealistic absolute values when regularized with the Marquardt-Levenberg scheme. Essentially, compensating relationships between terms containing electric and/or magnetic distortion are used in this growth. In a regularization with the minimum solution length criterion, the distortion parameters converge into a stable configuration after several iterations and attain reasonable values. The inversion algorithm was applied to a CSAMT field data set collected along a profile over a tunnel construction site at Hallandsåsen, Sweden. To avoid erroneous inverse models from strong anthropogenic effects on the data, two scalar transfer functions (one scalar impedance and one scalar vertical magnetic transfer function) were selected for inversion. Compared with a regularization of distortion parameters with the Marquardt-Levenberg method, the minimum-solution length criterion yielded smaller absolute values of distortion parameters and a horizontally more homogeneous distribution of electrical conductivity.

Description: Background: High-dose chemotherapy (HDCT) followed by autologous transplantation of hematopoietic stem cells (auto-HSCT) is an important component of treatment in multiple myeloma (MM). There is a standard method of controlled cryopreservation of HSC suspension. We found that the storage of native HSC suspension with temperature fluctuations from +3 °C to +5 °C during 72 - 120 hours does not significantly affect the content of CD34+ cells in the product, the index 7AAD- (7-AAD (7-aminoactinomycin - D) is a fluorescent marker that penetrates damaged cell membranes and binds to double-stranded DNA. Through 7AAD does not penetrate intact membranes, so living cells are not stained 7AAD with flow cytometry), and colony-forming ability (CFA) of HSC, as well as the recovery time of hematopoiesis in MM patients after auto-HSCT. Aim: To evaluate the effectiveness and safety of the method of storage of non-cryopreserved peripheral blood stem cells. Methods: 39 patients with MM were included in this study(male/female ratio 1.36:1). All the patients get standard immunochemotherapy programs and were in remission at the time of auto-HSCT. Patients were divided into two groups depending on the method of stem cell storage: group 1 - non-cryopreserved (n=20), group 2 - cryopreserved (standard) (n=19). An effectivity and safety were evaluated in such parameters as the number of CD34+ and 7AAD- cells, CFA after apheresis and before reinfusion of HSC. Also, we evaluated the number of platelets concentrate transfusions, the timing of engraftment of granulocytic and megakaryocytic blood sprouts, the length of hospital stays after auto-HSCT. Results: The results are presented in the comparison table of the evaluated parameters. Our data showed significantly reduce of episodes febrile neutropenia and cases of enteropathy. Conclusion: Thus, the proposed method of storage of HSC is not inferior to the traditional method with cryopreservation on such parameters as CD34+, 7AAD-, CFA, the number of platelets concentrate transfusions, terms of hematopoiesis restoration, length of hospital stay after HSCT, the number of complications. Table. Disclosures Shuvaev: Fusion Pharma: Consultancy; BMS: Consultancy; Novartis: Consultancy; Pfize: Honoraria.

Description: Background The risk-stratification systems are repeatedly updated in accordance with the emergence of new information about the prognostic impact of anomalies and other factors. The most extensive and modern system in this time is mSMART risk stratification involving many parameters such as genetic anomalies, albumin, beta-2-microglobulin, LDH, Plasma Cell S-phase and GEP levels. It is possible to use risk-adapted treatment programs with or without ASCT. Nevertheless, the role of complex karyotype, combination of genetic abnormalities and ASCT remains unclear. Aims To estimate the genetic abnormalities in patients with newly diagnosed multiple myeloma and define the role of risk-stratification and ASCT in prognosis of disease. Methods The study included 159 patients (median age 63 years, range 28 - 83; male: female ratio - 1:1.37) with NDMM. Metaphase cytogenetics on bone marrow samples was done by standard GTG-method. FISH analyses were performed according to the manufacturer's protocol for detection primary IgH translocations, 13q (13q14/13q34) deletion, 1p32/1q21 amplification/deletion, P53/cen 17 deletion (MetaSystems DNA probes). We additional searched the t(4;14), t(6;14), t(11;14), t(14;16) and t(14;20) in patients with IgH translocation. All patient was treated by bortezomib-based programs (VD, CVD, VMP, PAD). ASCT was performed at 42% patients. Results The frequency of genetic abnormalities in NDMM patients was 49% (78/159). IgH translocation was detected in 26.4% (42/159) patients: t(11;14) - 16.3% (26/159), t(4;14) - 5.0% (8/159); TP53/del17p - 5.6% (9/159); 1p32/1q21 amp/del - 12% (19/159); hypodiploidy - 3.1% (5/159); hyperdiploidy - 1.25% (2/159); del5q - 0,6% (1/159); other - not found. Combination two aberrations was discovered in 11.9% (19/159) patients, complex abnormalities (〉3 aberrations) - in 4.4% (7/159) patients. The median OS in "two aberration" and "complex abnormalities" groups were lower than in standard-risk mSMART 3.0 (normal, t(11;14), hypodiploidy, hyperdiploidy and other): 49 months, 26 months and was not reached, respectively (p=.00015). The median PFS for these groups was 12 months, 11 months and 30 months, respectively (p=.011). Differences between "two aberration" and "complex abnormalities" groups were not find (p〉 .05). We modified high-risk (gain 1q, p53 mutation, del 17p deletion, t(4;14), t(14;16), t(14;20), R-ISS stage III, double and triple hit myeloma) mSMART 3.0 by adding "two aberration" and "complex abnormalities" groups on based the OS and PFS results. The final analysis was based on the results of the complex examination of 87 patients: 53 patients in standard-risk group and 34 patients in high-risk group. The median OS in standard-risk mSMART 3.0 was not reached, in high-risk mSMART 3.0mod - 48 months; 5-years OS was 62% and 38%, respectively (p=0.0073). The median PFS was 43 and 29 months, respectively (p=.09). The best results of OS and PFS were reach in both groups of patient who performed ASCT. The median OS in standard-risk mSMART 3.0 with ASCT (n=37) was not reached, in high-risk mSMART 3.0mod with ASCT - 48 months (n=20); standard-risk mSMART 3.0 without ASCT - 40 months (n=16); in high-risk mSMART 3.0mod without ASCT - 22 months (n=14); 5-years OS was 81%, 60%, 33% and 28%, respectively (p=0.0015). The median PFS was not reached, 46, 22 and 19 months, respectively (p=.017). Conclusions The combination of two aberrations and complex abnormalities is unfavorable prognostic markers. The median OS and PFS was higher in standard-risk than high-risk group according mSMART 3.0mod. The ASCT can improve treatment's outcomes and life expectancy especially in patients with high-risk. It can be useful for update risk stratification in a future. Disclosures Shuvaev: Novartis: Consultancy; Pfize: Honoraria; Fusion Pharma: Consultancy; BMS: Consultancy.

Description: Background: The paradigm of the treatment mantle cell lymphoma (MCL) has changed due to development of newer agents (such as ibrutinib, lenalidomide, temsirolimus). Considering that the scheme of using the newer drugs implies permanent drug intake (before disease progression), which helps prevent the early relapses. With a high degree of probability, it can be assumed that MCL, in the future can be withdrawn from the group of aggressive and relapsing lymphomas. Evaluation and monitoring of the minimal residual disease (MRD) in patients with MCL allows to predict the course of the disease and optimize the strategy for maintaining this category of patients. Aim: To assess influence of MRD negative (MRDneg) status on the duration of progression free survival (PFS) and overall survival (OS). Method: In this study were included 33 patients with MCL (male/female ratio 3:1), age 51 to 82 years (median 64 years). The median of follow-up duration is 80.7 months (range 0.7-147.1). Median of therapy lines - 1 (range 1-5). With rituximab-containing chemotherapy regimens were treated 25 patients (R-CHOP - 12, RFC - 5, RBV - 3, RB - 2, R-DHAP - 1, R-Hyper-CVAD - 1, RVc-CAP - 1); ibrutinib - 3, lenalidomide - 3 and temsirolimus - 1. Autologous stem cell transplantation (AutoSCT) was performed in 7 patients (21.2%). Maintenance therapy received 23 patients (69.7%): rituximab - 20, ibrutinib - 1, lenalidomide - 1 and temsirolimus - 1. During the follow-up period, 9 patients (27.2%) died: progression of the disease - 5, other reasons - 4. The evaluation of MRD status was carried out using 5-color flow cytometry on bone marrow samples after completion of induction therapy. The absent of MRD was detected when less than 1 tumor cell was detected per 10000 leukocytes (10-4). Results: Complete remission (CR) was achieved in 54.5% (n=18), partial remission (PR) - 45.5% (n=15). Patients were divided into two groups depending on MRD status: group MRD positive (MRDpos) (n=12) and group MRD negative (MRDneg) (n=21). The frequency of achievement of MRDneg status was 63.6% (CR - n=15, PR - n=6). Noted, that all patients (n=7) who underwent AutoSCT achieved MRDneg status after induction therapy and kept it after consolidation with AutoSCT. Disease progression in MRDpos group was state in 11 patients (91.7%), in MRDneg group - 6 (28.6%) (р=0.0005). Patients with MRDpos status who underwent maintenance therapy achieved MRDneg status in 8/12 cases. One patient, after completion R-CHOP + AutoSCT followed by a two-year maintenance program of rituximab, retained MRDneg status. A year later, during the control survey, MRDpos status was recorded. This patient was resumed maintenance therapy with rituximab. MRDneg status is achieved after 6 months from the beginning of maintenance therapy. Median PFS in group MRDneg was not achieved, in group MRDpos - 12.5 months (р=0.001). Medians OS were not achieved in both groups. 5-year OS were: group MRDneg - 83.8% and group MRDpos - 73.3%. 10-year OS were: group MRDneg - 64.4% and group MRDpos - 58.7%. When comparing OS in patients among all groups no significant differences were found, which is probably due to a small number of events (р〉0.05). Conclusion: Our data demonstrate that achievement MRDneg remissions determine duration of response on ongoing therapy and significant increase of PFS duration. Presently, MRD detection in patients with MCL is important part of complex assessment of effectiveness therapy and it need to be studied more. Figure. Figure. Disclosures No relevant conflicts of interest to declare.