Bulk Reduction Research Articles

Selective Recovery of Tin from Electronic Waste Materials Completed with Carbothermic Reduction of Tin (IV) Oxide with Sodium Sulfite

A new approach for the thermal reduction of tin dioxide (SnO2) in the carbon/sodium sulfite (Na2SO3) system is demonstrated. The process of tin smelting was experimentally optimized by adjusting the smelting temperature and amounts of the chemical components used for the thermal reduction of SnO2. The numbers obtained are consistent with the thermodynamic characteristics of the system and molar fractions of reactants derived from the proposed mechanism of the SnO2 thermal reduction process. They reveal that the maximum yield of tin is obtained if masses of C, Na2SO3 and SnO2 are approximately in the ratio 1:2:3 and the temperature is set to 1050 °C. The key role in the suggested mechanism is the thermal decomposition of Na2SO3. It was deduced from the available experimental data that the produced sulfur dioxide undergoes carbothermic reduction to carbonyl sulfide—an intermediate product involved in the bulk reduction of SnO2. Replacing sodium sulfite with sodium sulfate, sodium sulfide and even elemental sulfur practically terminated the production of metallic tin. The kinetic analysis was focused on the determination of the reaction orders for the two crucial reactants involved in the smelting process.

Feynman rules and loop structure of Carrollian amplitudes

In this paper, we derive the Carrollian amplitude in the framework of bulk reduction. The Carrollian amplitude is shown to relate to the scattering amplitude by a Fourier transform in this method. We propose Feynman rules to calculate the Carrollian amplitude where the Fourier transforms emerge as the integral representation of the external lines in the Carrollian space. Then we study the four-point Carrollian amplitude at loop level in massless Φ4 theory. As a consequence of Poincaré invariance, the four-point Carrollian amplitude can be transformed to the amplitude that only depends on the cross ratio z of the celestial sphere and a variable χ invariant under translation. The four-point Carrollian amplitude is a polynomial of the two-point Carrollian amplitude whose argument is replaced with χ. The coefficients of the polynomial have branch cuts in the complex z plane. We also show that the renormalized Carrollian amplitude obeys the Callan-Symanzik equation. Moreover, we initiate a generalized Φ4 theory by designing the Feynman rules for more general Carrollian amplitude.

Direct and converse piezoelectricity of thickness tuned BCZT ceramics: toward efficient bilayered magnetoelectric devices

Here we report the effect of thickness reduction of bulk 0.5(Ba0.7Ca0.3)TiO3-0.5Ba(Ti0.8Zr0.2)O3 (BCZT) pellet on its direct and indirect piezoelectric properties. Upon reducing the thickness to 0.3 mm, the pellet shows a very high electrostrain of ∼0.7% and piezoelectric coefficient of ∼353 pC/N which were ∼0.14% and 258 pC/N for the 1 mm thick sample. These results have been correlated with the reduction in hardness and mutual mechanical clamping between the grains due to the reduced thickness of BCZT. Due to this improved strain sensitivity, the bilayered magnetoelectric (ME) devices of BCZT with magnetostrictive CoFe1.9Bi0.1O4 (CFBO) pellet have also shown gradually improved ME coupling coefficient ( αME ) with reduced BCZT thickness ( αME = 27 and 66 mV·cm−1·Oe−1 for 1 and 0.3 mm BCZT thickness, respectively). This demonstrates the possible applicability of thickness tuned BCZT pellets for various technological purposes.

Quality Evaluation of Fermented Pre Gelatinized Unripe Plantain and Soybean Based Complementary Foods 1: Physicochemical, Sensory and Rheological Properties

Aims: This study aimed at evaluating the effect of the degree (%) of starch gelatinization (G) and fermentation (F) on the physicochemical characteristics of the flours and also the sensory and flow properties of the gruels of unripe plantain fruits and soybean seeds based complementary foods. Study Design: Completely randomized design Place and duration of the Study: This study was carried out in Makurdi, Benue State, Nigeria, between January and November 2023. Methodology: Plantain slices heated to obtain 10% to 100% starch gelatinization were subjected to accelerated natural fermentation followed by drying and milling to yield fermented (F) flours. Non-gelatinized (NG) and nonfermented (NF) lots served as controls. The flours were each combined with soybean flour to obtain 16 g protein/100 g of each mixture based on the proximate compositions of the inputs using material balancing technique. The flours’ oil absorption capacities (OAC), water absorption capacities (WAC), packed bulk densities (PBD), sensory attributes (taste, mouth feel, appearance, overall acceptability) and flow properties of their gruels were evaluated using standard methods. Significant differences and separation of the data means were achieved by Duncan multiple range and Turkey’s tests using an SPSS package, respectively. Results: Gelatinization and fermentation increased WAC and OAC, but decreased packed bulk density (PBD) of the flours with concomitant reduction in pH, viscosities and improved sensory attributes of the gruels. Generally, viscosities increased with increase in slurry concentration and decreased with increase in temperature and shear rates. The flow behavior indices ranged from 0.27 to 0.64, with lower values in gelatinized and fermented samples, showing more pseudoplastic behavior in pretreated samples. Conclusion: Gelatinization and natural fermentation are therefore adaptable technologies, especially at rural levels, to improve acceptability and bulk reduction of resistant starch-based complementary foods.

Promotional effects of Nb2O5 on ceria doped Ni catalysts for selective hydrogenation of 1,3-butadiene to butenes: Combined experimental and DFT approach

Developing low cost, active and selective catalysts that would replace the more deployed noble metals is desirable for hydrogenation of 1,3-butadiene. Herein, we prepared Ni catalysts supported on niobium-cerium oxides and characterization was carried out with TGA, XRD, H2-TPR, H2-TPD, HR-TEM, XPS, FTIR, N2 adsorption–desorption, and EDS mapping. Density functional theory (DFT) computes the reaction energies controlling the 1,3-butadiene hydrogenation. H2-TPR revealed that the inclusion of niobium oxide in the catalysts confer stronger metal support interaction that promotes the surface and bulk reduction of cerium oxide and leads to the improvement in the formation of surface Ce3+ as confirmed from the XPS analysis. 1,3-butadiene conversion was tested between 100 °C-350 °C and the catalysts exhibit high conversion at lower Ni loading. We found that the niobium inclusion directed the selectivity towards near complete butene formation even at higher temperature. The onset of decline in activity was observed at temperatures above 250 °C with the simultaneous formation of propene and propane and the disappearance of butane. Guided by the reaction results and the temperature programmed oxidation analysis (TPO), we proposed the reaction mechanism leading to the deactivation, and this entails butane decomposition to propene and surface carbene, while propane is formed from propene, the surface carbene occasioned in the formation of harmful carbon as evident from TPO results. Carbonaceous species formed on the catalysts were minimized on the niobium containing catalysts.

Simultaneous Reduction of Bulk and Contact Thermal Resistance in High‐Loading Thermal Interface Materials Using Self‐Assembled Monolayers

AbstractThermal interface materials (TIMs) play a pivotal role in the transfer of heat from high‐temperature sources, such as CPUs, to heat sinks in power electronics. The effectiveness of grease‐type TIMs is determined by their effective thermal impedance (REFF), which hinges on optimizing both the specific bulk (RB) and contact (RC) thermal resistances. Achieving concurrent optimization of these resistances poses a significant challenge, especially in high filler loading TIMs, typically above 76 vol%. This research leverages interface engineering through Self‐Assembled Monolayers (SAMs) to address this challenge. A substantial decrease in REFF is realized to 0.169 K cm2 W−1, a tenfold enhancement compared to non‐SAM treated TIMs, which exhibit REFF values of 2.265 K cm2 W−1. This leap in performance is primarily ascribed to the reduced surface energy of SAM treated Al2O3, leading to lower particle‐to‐particle Van der Waals forces, thereby improving particle dispersion and strengthening interfacial bonds. Furthermore, longer carbon chains in SAMs result in increased RB, yet a decrease in RC, due to the chains' capacity for enhanced energy absorption and molecular entanglement. The investigation underscores the significance of shorter‐chain SAMs in fine‐tuning thermal resistance, highlighting the crucial role of molecular architecture in the design of advanced TIMs.

Holographic dictionary from bulk reduction

We propose a holographic dictionary which comes from reducing the bulk theories in an asymptotically flat spacetime to its null infinity. A general boundary theory is characterized by a fundamental field, an infinite tower of descendant fields, constraints among the fundamental field and its descendants, as well as a symplectic form. For the Carrollian diffeomorphisms, we can construct the corresponding Hamiltonians which are also the fluxes from the bulk, and whose quantum operators realize this algebra with a divergent central charge. This central charge reflects the propagating degrees of freedom and can be regularized. For the spinning theory, we need a helicity flux operator to close the algebra which relates to the duality transformation. Published by the American Physical Society 2024

Gettering of iron by aluminum oxide thin films on silicon wafers: Kinetics and mechanisms

Metallic impurities in the silicon wafer bulk are one of the major efficiency-limiting factors in silicon solar cells. Gettering can be used to significantly lower the bulk metal concentrations. Aluminum oxide thin films from plasma-enhanced atomic layer deposition (PE-ALD) have been reported to getter iron from silicon wafers. However, its gettering mechanism and kinetics remain unclear. In this study, by experimentally monitoring the kinetics of iron reduction in the silicon wafer bulk, aluminum oxide gettering of iron is shown to be caused by a segregation mechanism. Fitting the experimental iron reduction kinetics by the simulation of a segregation gettering process based on various diffusion scenarios suggests that the gettering kinetics is limited by both the diffusivities of iron in the silicon wafer bulk and in the aluminum oxide film. The activation energy of the segregation gettering process (negative meaning exothermic reaction) is estimated to be −0.47 ± 0.16 eV for the investigated as-deposited PE-ALD aluminum oxide film at 550–900 °C, and −0.35 ± 0.06 eV at 400–900 °C for the same film after a 400 °C forming gas anneal (FGA), i.e., after activating the passivation effect of the film. Capacitance–voltage measurements of the films indicate a higher surface defect density in the as-deposited films as compared to the FGA-activated films, which suggests a possible correlation between the surface defect density and gettering.

A review on the manufacturing techniques for textile based antennas

An antenna is a medium of communication in electronic systems and one of its branches is known as wearable antenna (embedded in clothing or other wearables). Antennas are found in a wide range of applications such as medical, military, sports, safety, fitness, satellite communication etc. Textile based antennas are considered a replacement of conventional communication systems in E-textiles as they are more flexible and comfortable as compared to their metallic counterparts and more efficient than transmission wires. Electronic wiring which is commonly used for data transmission is susceptible to damage because of bending or stretching in wearables and may cause interferences between signals and time delays. One of the most significant advantages of wearable antennas is the reduction of bulk of electronic components as they can act as a sensor and communicator at a time. The cost can also be reduced this way. The current work focuses on the review of different manufacturing techniques for wearable antennas. The scope of this review is to highlight main techniques, their advantages and limitations in comparison with each other as well as to describe the available solutions of associated problems. The findings of this review could be fruitful for researchers to find out the best manufacturing technique for antennas in their perspective. Visual Abstract [Formula: see text]

Management of Central and Peripheral Nervous System Tumors in Patients with Neurofibromatosis.

Neurofibromatosis type I (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis represent a diverse group of genetic tumor predisposition syndromes with a shared feature of tumors affecting the peripheral nerve sheaths. PURPOSE OF REVIEW: Many advancements have been made in understanding the biologic underpinnings of these conditions, and in 2016 the first drug was approved by the FDA to treat pediatric symptomatic unresectable plexiform neurofibromas. RECENT FINDINGS: Mek inhibitors have provided a much-needed therapeutic avenue for NF1 patients with unresectable plexiform neurofibromas (PN), both for reduction of tumor bulk and for improvement in symptoms. Selumetinib is the first FDA approved drug for PN, but is only approved for children. Some research suggests that alternative Mek inhibitors and other mixed tyrosine kinase inhibitors may have better efficacy in adults. Vascular endothelial growth factor (VEGF) inhibitor bevacizumab can prolong hearing and delay the need for surgery in NF2 patients with bilateral vestibular schwannomas. This article provides an update regarding considerations and approaches when treating the tumors associated with the neurofibromatoses (NF), including risk and prognosis metrics, clinical trial results, surgical techniques, and radiation therapy recommendations.

Electron characteristics and dynamics in sub-millimeter pulsed atmospheric dielectric barrier discharge

The discharge characteristics and mechanism of sub-millimeter pulsed dielectric barrier discharge in atmospheric-pressure helium are investigated experimentally and theoretically, demonstrating that when the discharge gap distance is reduced from 1.00 mm to 0.20 mm, the discharge ignition time is reduced to approximately 40 ns and discharge intensity is enhanced in terms of the discharge optical emission intensity and density of the plasma species, (energetic electrons with energy above 8.40 eV). The simulated results show that as the discharge gap distance is further reduced to 0.10 mm, the number of energetic electrons decreases, which is attributable to the contraction of plasma bulk regime and reduction of electron density in the discharge bulk. Conversely, the proportion of energetic electrons to the total electrons in the discharge monotonically increases as the discharge gap distance is reduced from 1.00 mm to 0.10 mm. It is proposed that a gap distance of 0.12 mm is optimal to achieve a high concentration and proportion of energetic electrons in sub-millimeter pulsed atmosphere dielectric barrier discharge.

Structural, morphological, dielectric properties, impedance spectroscopy and electrical modulus of sintered Al6Si2O13–Mg2Al4Si5O18 composite for electronic applications

In this study, the sol-gel method of low-temperature synthesis was utilized to create mullite/cordierite precursor powder. The materials (TEOS) Si(C2H5O)4, Al(NO3)3.9H2O and Mg(NO3)2 were utilized as source of SiO2, Al2O3, and MgO oxides respectively in order to create mullite/cordierite precursor gel with various concentrations and designations (MC00, MC10, MC20, MC30, MC40, and MC50). Crystalline phases were seen and described using scanning electron microscopy (SEM) and powder X-ray diffraction (XRD). After the powder was formed at 1600 °C for an hour, its sintering was looked at. For all mixes, as the cordierite concentration rises, the bulk density rises and the open porosity decreases. The existence of a vitreous phase may be the cause of the rise in bulk density and reduction in open porosity seen with rising temperatures.The dielectric characteristics of the samples have been examined at room temperature; the relative dielectric constant (εr), loss tangent (tanδ), and dielectric characteristics were assessed at frequencies of 0.1 Hz, 1, 10, 100, and 1000 kHz. At 1 kHz, the relative dielectric constant values are closest to those of mullite (εr = ∼5 to ∼ 6), and c at 1 kHz. On the other hand, the lowest dielectric losses were observed (tanδ from ∼0.06 to ∼ 0.04). The Electrical properties, electrical resistivity, AC conductivity, impedance spectroscopy, electrical modulus, and the relative quality factor (QF) of pure mullite and mullite/cordierite composite sintered at 1600 °C for 1 h (MCyy) samples were investigated as a function of cordierite content at varied frequencies (0.01 Hz, 1 kHz, 100 kHz, and 1000 kHz). The hardness (HV) and coefficient of thermal expansion (CTE) of the composite material that underwent sintering at a temperature of 1600 °C were determined by the use of a hardness tester and a dilatometer, respectively. The rise in temperature, coupled with an equal quantity of cordierite, resulted in an elevation of the apparent density and a reduction in the open porosity. In the case of the specimen subjected to sintering at a temperature of 1600 °C, the introduction of cordierite content in the range of 0–40% resulted in an observed rise in HV value from 9.15 to 12.99 GPa. However, a further increase in cordierite content to 50% led to a decrease in HV value to 10.99 GPa. Nevertheless, the CTE value throughout the temperature range of 50–1200 °C exhibited a consistent decline, ranging from 5.37 × 10−6 to 2.32 × 10−6 K−1. Notably, the composite material consisting of 50 wt% cordierite had elevated HV and the most minimal CTE value.

Energy saving potential of interstage screen fractionation for production of board grade BCTMP

Over the last few decades, the continuing decline in mechanical pulp-based grades has led pulp producers to modify operations and implement measures to reduce production costs in order to stay competitive. In spite of a considerable effort to reduce energy consumption, the latter is still a major portion of production costs in the process of making bleached chemithermomechanical pulp (BCTMP). In this study, we evaluated the impact of interstage screening fractionation (ISSF) and secondary refining strategy for producing BCTMP with the objective of reducing refining energy consumption while maintaining or improving bulk and strength properties. In the first step and to establish a baseline for a mill’s existing configuration, the collected primary refined pulp and reject streams from the ISSF were refined in a high consistency (HC) refiner to target freeness levels. The accepts and refined rejects streams were recombined, and their properties were compared to those of the refined primary pulp. The results showed that, at a given freeness of 400 mL and compared to the control case (without fractionation), the ISSF using an 0.070 in. basket followed by rejects refining could lead to about 25% energy saving in the second stage HC refining. Handsheet properties showed that utilization of ISSF could produce BCTMP with higher bulk and similar average fiber length and tear index. However, a slight reduction in tensile strength was observed. In the second set of trials, the primary refined pulp and the rejects from the ISSF using the 0.070 in. basket were refined by a low-consistency (LC) refiner. The results showed that, at the same freeness of 400 mL and compared to refined primary pulp, the ISSF saved about 26% in net LC refining energy. At a specific edge load (SEL) of 0.4 J/m, the produced pulp had similar bulk and strength properties compared to those of the control sample. A higher SEL of 0.6 J/m in LC refining could further decrease net refining energy consumption; however, it also led to reduction in fiber length, bulk, and strength properties.

Temperature Dependence Modeling and Thermal Sensitivity Reduction of Bulk Micromachined Silicon MEMS Lamé Resonators

Temperature Dependence Modeling and Thermal Sensitivity Reduction of Bulk Micromachined Silicon MEMS Lamé Resonators

Reduction of bulk and surface defects in inverted methylammonium- and bromide-free formamidinium perovskite solar cells

Reduction of bulk and surface defects in inverted methylammonium- and bromide-free formamidinium perovskite solar cells

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Background: Recent studies demonstrated that classical Hodgkin lymphoma (cHL) is characterized by chromosome 9p24.1 amplification with associated overexpression of PD-1 ligands and JAK2 tyrosine kinase activation. JAK2 signaling augments tumor cell proliferation. Given this biology, we tested the combined inhibition of PDL1 pathway and JAK2 signaling in cHL patients who had progressed after prior PD-1 blocking therapy. Methods: This is a Phase I/II multicenter, open-label, dose escalation/dose-expansion study to evaluate the safety and tolerability of JAK2 inhibitor ruxolitinib when combined with nivolumab in patients with R/R cHL (NCT03681561) who fail prior check-point inhibitor. Ruxolitinib was administered at 3 dose levels: 10, 15 or 20 mg orally twice a day continually with nivolumab at fixed dose 3 mg/kg IV every 2 weeks. Planned duration of therapy was 2 years. Results: We enrolled 21 patients with median age 41 years (range 22–76); 67% were males. Patients were 3.4 years from diagnosis (median; range 0.9–16.7 years), 81% had stage III-IV and 89% had prior stem cell transplant. All patients had experienced progressive disease following prior CPI; 78% were resistant to CPI. Ruxolitinib MTD of 20 mg BID was reached without DLTs. Median cycles administered was 9 (range 3–28). The combination was well tolerated; most AEs were grade 1 and 2. Three patients experienced immune mediated adverse events (LFT elevation: 3 Gr 1 and 1 Gr 2; 1 Gr 3 pneumonitis); all were reversible. Median follow-up was 20.7 months (range 3–52 months). In 19 patients evaluable for response (by LYRIC criteria), best disease control rate was 63% (12 of 19); including 5 complete response (26%), 3 partial response (16%) and 3 patients had stable disease (SD, 16%; with tumor bulk reduction ranging from 3 to 48%). One patient had indeterminate response (negative biopsy of new PET-avid site). Median duration of responses was 16.5 months (range 5.8 to 20.4 months). Two patients died, both with progressive disease and one from complications of subsequent experimental therapy. Progression-free survival at 2 years was 45% (95% CI: 22–66%). Correlative analysis demonstrated a ruxolitinib-driven modulation of classical monocytes and myeloid derived suppressor cells suggesting a synergistic antitumor effect with nivolumab. Correlative and in vitro data on mechanism of synergy will be presented. Conclusions: Therapy combining ruxolitinib with nivolumab is well tolerated and yield encouragingly high remission rates and durable responses in patients who failed previous CPI. Pharmacodynamic and correlative analyses suggest synergistic effect on adaptive and innate immune systems. The research was funded by: Incyte and BMS sponsored this trial as investigator initiated study Keywords: Hodgkin lymphoma, Immunotherapy Conflicts of interests pertinent to the abstract. V. Bachanova Research funding: Incyte and BMS supported this trial

Intratumoral injection of oncolytic virus (H101) in combination with concurrent chemoradiotherapy for locally advanced cervical cancer

ObjectivesTo evaluate the efficacy of primary tumor bulk reduction and the safety of concurrent chemoradiotherapy in combination with H101, a type of oncolytic virus, for the treatment of locally advanced...

Toxicity evaluation of iron oxide nanoparticles to freshwater cyanobacteria Nostoc ellipsosporum.

The extensive usage of iron oxide nanoparticles (FeO NPs) in commercial and biomedical applications raises the risk of releasing their remains into the aquatic ecosystems and this could possibly cause cytotoxic effects on aquatic organisms. Thus, the toxicity assessment of FeO NPs on cyanobacteria, which are primary producers at the bottom of food chain in aquatic ecosystems, is essential to gain information about the potential ecotoxicological threat on aquatic biota. The present study investigated the cytotoxic effects of FeO NPs on Nostoc ellipsosporum using different concentrations (0, 10, 25, 50 and 100mg L-1) to track the time-dependent and dose-dependent effects and compared with its bulk equivalent. In addition, the impacts of FeO NPs and bulk counterpart on cyanobacterial cells were assessed under nitrogen as well as nitrogen-deficient conditions, because of ecological role of cyanobacteria in nitrogen fixation. The study revealed that the highest protein content was observed in the control in both types of BG-11 media compared to treatments of nano and bulk particles of Fe2O3. A 23% reduction in protein in nanoparticle treatment and a 14% reduction in bulk treatment at 100mg L-1 was observed in BG-11 medium. At same concentration, in BG-110 media, this decline was even more intense with 54% reduction in nanoparticle and a 26% reduction in bulk. Catalytic activity of catalase and superoxide dismutase was found to be linearly correlated with the dose concentration for nano and bulk form in BG-11 as well as BG-110 media. The increased levels of lactate dehydrogenase act as biomarker of the cytotoxicity brought on by nanoparticles. Optical, scanning electron, and transmission electron microscopy all demonstrated the cell entrapment, nanoparticle deposition on the cell surface, cell wall collapse and membrane degradation. A cause for concern is that nanoform was found to be more hazardous than bulk form.

Zooplankton‐derived dissolved organic matter composition and its bioavailability to natural prokaryotic communities

AbstractZooplankton grazing onphytoplankton promotes the release of particulate and dissolved organic matter (DOM) into the water column and therefore plays a key role in organic matter cycling in aquatic systems. Prokaryotes are the main DOM consumers in the ocean by actively remineralizing and transforming it, contributing to its molecular diversification. To explore the molecular composition of zooplankton‐derived DOM and its bioavailability to natural prokaryotic communities, the DOM generated by a mixed zooplankton community in the coastal Atlantic off Spain was used as substrate for a natural prokaryotic community and monitored over a ~ 5‐d incubation experiment. The molecular composition of solid‐phase extracted DOM was characterized via Fourier‐transform ion cyclotron resonance mass spectrometry. After ~ 4 d in the zooplankton‐derived DOM amended incubation, the prokaryotic community demonstrated a 17‐fold exponential increase in cell number. The prokaryotic growth resulted in a reduction in bulk dissolved organic carbon concentration and the zooplankton‐derived DOM was considerably transformed at molecular and bulk elemental levels over the incubation period. The C : N ratio (calculated from the obtained molecular formulae) increased while the functional diversity decreased over the incubation time. In addition, molecular indices pointed to a reduced bioavailability of DOM at the end of the experiment. These findings show that zooplankton excreta are a source of labile organic matter that is quickly metabolized by the prokaryotic community. Therefore, a fraction of carbon is shunted from transfer to secondary consumers similarly to the viral shunt, suggesting that the zooplankton–prokaryotic interactions play an important role in the ocean's carbon cycle.

Exploratory Results of PET-CT and Residual Lymph Node Fine Needle Aspiration of Patients Treated with First-Line Venetoclax and Ibrutinib for CLL/Sll; First Interim Analysis of the Phase 2 HOVON 158/Next STEP Trial

Background: Fixed-duration treatment of chronic lymphocytic leukemia (CLL) with venetoclax combined with a BTK-inhibitor(i) results in prolonged progression free survival (PFS). Undetectable levels of minimal residual disease (uMRD) reach an early plateau and are highly predictive for PFS in case of venetoclax in combination with anti-CD20, but kinetics are different when combined with a BTK-i. MRD-levels mirror disease activity in blood (PB) and bone marrow but much less of lymph node (LN) disease, the suspected critical site of CLL proliferation and development of resistance. Although regular CT-scans do provide information on tumor-bulk, there is a high uncertainty concerning the bio-clinical significance of the frequently observed minimally enlarged LN. The NEXT-STEP trial evaluates the efficacy of adding 6 cycles ibrutinib and obinutuzumab for treatment naive patients who do not achieve complete remission (CR) and uMRD after 3 cycles of ibrutinib lead-in and 12 cycles of combined ibrutinib and venetoclax. The first preplanned interim analysis evaluates safety and efficacy for the first 30 eligible patients until the end of cycle 8. In addition, exploratory analyses of 18F-fluorodeoxyglucose (FDG) PET-CT as well as presence of CLL cells in residual LN by fine-needle aspirations (FNA) were performed. We here present this interim analysis. Methods: HOVON 158/NEXT STEP trial is an open-label, single arm phase 2 study. Eligible patients with untreated CLL or small lymphocytic lymphoma (SLL) receive three 28 days cycles of ibrutinib followed by 12 cycles of combined ibrutinib and venetoclax. IwCLL response and MRD bone marrow are assessed after cycle 15. Patients achieving CR with uMRD4 (8-colour flow cytometry, <10-4) stop treatment. Intensification with an additional 6 cycles of ibrutinib combined with obinutuzumab is provided for patients with MRD positivity and/or less than CR. After cycle 8 an exploratory analysis is done with locally assessed Deauville score (DS) on PET-CT. In addition, if at end of cycle 8 a LN > 1.5 cm is present on physical examination or CT scan and located cervical, axillar or inguinal (for safe accessibility), a fine needle aspiration (FNA) by ultrasound is requested. Obtained cells are centrally analyzed by flow cytometry. Results: Median age was 69 years (range 34-85), 70% were male. One patient had SLL. CIRS score > 6 was found in 6 patients (20%). Median eGFR was 65 ml/min (range 39-132). Median lymphocyte count was 157.3 x 109/l (range 2.50-475). CLL-IPI score was low and intermediate in one (3%) and 6 (20%) and high and very high in 18 (60%) and one (3%) patients, respectively. Del (17p)/TP53 mutation was found in 3 patients (10%). Genomic complexity (≥ 3 aberrations) was found in 3 patients (10%). Overall response rate based on PB and CT scan after cycle 8 was 100%. Levels of responses are depicted in table 1. One patient discontinued therapy during the first 8 cycles, due to adverse events. No progression events or death have occurred and no new safety signals were reported at interim analysis. Of all the PET-scans at baseline 13 (43%) demonstrated an increased uptake (DS4) and 5 (17%) uptake > mediastinal blood pool (DS3). In all but one patient DS decreased after 8 cycles; 1 (3%) remainded DS4, 2 (7%) had DS3, 9 (31%) had uptake equal or below mediastinal blood pool (DS2) and 16 (55%) had no uptake (DS1). In 1 patient PET was not performed. Of 13 patients with enlarged LN after cycle 8, FNA could be done in 9 patients, of which 5 contained sufficient number of cells for analysis. FNA was performed in all 3 patients with DS3-4 because of remaining enlarged LN. In all cases, persistent nodular CLL cells were detected by flow cytometry. In 4 of the 5 patients, MRD levels were higher in the LN as compared to PB. The patient with DS4 demonstrated the highest CLL cells percentage in FNA (Figure 1). Conclusion: Three cycles of ibrutinib followed by 5 cycles of ibrutinib and venetoclax results in tumor bulk reduction with a decrease in metabolic uptake on PET-CT in all but one patient. We demonstrated persistent CLL cells by flow cytometry in enlarged LN, suggesting residual LN serve as a sanctuary of CLL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal