Residual Induction Research Articles

Delaying pegaspargase during induction in adults with acute lymphoblastic leukaemia is associated with lower risk of high-grade hepatotoxicity without adversely impacting outcomes.

Pegaspargase is a key drug for the treatment of younger adults with acute lymphoblastic leukaemia (ALL). Pegaspargase-associated hepatotoxicity is most common during induction, and its incidence increases with age and body mass index (BMI). We hypothesized that the delayed administration of pegaspargase during induction is associated with lower risk of hepatotoxicity while retaining efficacy. We retrospectively reviewed 141 adult patients with newly diagnosed ALL who received pegaspargase during induction from November 2013 to February 2024. There were 78 (55.3%) patients who received early pegaspargase (EP) on day 4 and 63 (44.7%) patients who received delayed pegaspargase (DP) on day 15. High-grade hepatotoxicity (grade ≥ 3 transaminitis and/or hyperbilirubinaemia) occurred more frequently in the EP group (p = 0.06). Rates of complete remission and negative minimal residual disease post induction were not different between cohorts. Univariate logistic regression analysis showed that BMI and age significantly predicted an increased risk of high-grade hepatotoxicity while DP was associated with a lower risk (odds ratio = 0.44; p = 0.04). Overall survival and event-free survival were not significantly different between cohorts. Delaying pegaspargase administration from day 4 to day 15 during induction cycle in adults with ALL might reduce the risk of high-grade hepatotoxicity without adversely impacting clinical efficacy outcomes.

Changes in magnetic characteristics of pipes during hydraulic and pneumatic tests of trunk pipelines

To identify the zones with the highest tensile stresses and deformations, a two-parameter magnetic method based on the measurement of coercive force and residual magnetic induction was applied. For realization of the method a mobile hardware and software complex DIUS-1.21M with an electromagnetic U-transducer was used, which was located along the pipe axis and along the pipe ring. Measurements were carried out on three pipes: in the first one magnetic characteristics were measured in the absence and under the influence of internal pressure; in the second and third ones — before the test and after the pipe fracture. It was revealed that internal pressure leads to the growth of residual magnetic induction in all zones both along the axis and along the ring, which indicates the occurrence of axial and circular tensile stresses in these zones, and the change of coercivity occurred ambiguously. It was found that fracture significantly increases the scatter of magnetic characteristics, which is explained by the complex nature of the stress-strain state of the fractured object.

Magnetic properties and structure of carbon steel samples manufactured by selective laser melting and subjected to fatigue tests

This study investigates the magnetic properties and structure of 09G2S steel samples fabricated using casting and selective laser melting methods. Fatigue bending tests with cantilever fixation were performed to analyze these properties. It was found that the fatigue curve for 3D-printed steel lies below that of cast steel with a similar chemical composition. Both the coercive force and residual magnetic induction are lower near the fracture site. The greater the number of cycles to failure, the smaller the difference in coercive force and residual magnetic induction in different parts of the sample. The nature of fatigue failure differs between cast and 3D-printed steel. The cast 09G2S steel sample exhibits a straight and homogeneous fatigue fracture without visible crack initiation sites. In contrast, the 3D-printed steel samples show heterogeneous fractures with localized zones of failure and tear-off ridges.

ABOUT THE POSSIBILITY OF USING CORROSION-RESISTANT STEEL 08X22H6T IN THE DESIGNS OF MAGNETIC COUPLINGS AND MAGNETIC SYSTEMS

The influence of the brand of the material from which the magnetic conductors are made on the power characteristics of the magnetic system and magnetic coupling with highly coercive permanent magnets Nd–Fe–B with a residual magnetic induction of 1.1 T is considered. The material of the magnetic conductors is steel 15 or corrosion-resistant steel 08Х22H6T. On average, in the range of air gaps between sections of the magnetic system from 4 to 10 mm, the decrease in the specific shear force with magnetic conductors made of corrosion-resistant steel 08Х22Н6T, relative to magnetic conductors made of steel 15 is 18.15 %.

THE INFLUENCE OF THE BRAND OF THE MATERIAL FROM WHICH THE MAGNETIC CORES ARE MADE ON THE POWER CHARACTERISTICS OF THE MAGNETIC SYSTEM

The influence of the grade of the material from which the magnetic conductors are made on the power characteristics of the magnetic system and magnetic coupling with highly coercive permanent magnets Nd–Fe–B with a residual magnetic induction of 1.22 T is considered. The material of the magnetic conductors is steel 15, steel 09Г2C and corrosion-resistant steel 08Х22H6T. On average, in the range of air gaps between sections of the magnetic system from 4 to 10 mm, the decrease in the specific shear force with magnetic conductors made of corrosion-resistant steel 08Х22Н6T, relative to magnetic conductors made of steel 15 is 17.88 %. The increase in the specific shear force with magnetic conductors made of steel 09Г2C relative to magnetic conductors made of steel 15 depends on the value of the air gap between the sections of the magnetic system and varies from 2.53 to 11.81 %.

Impact of residual induction number of non-pulmonary vein foci on the 2-year outcomes in patients with paroxysmal atrial fibrillation.

Residual non-pulmonary vein (PV) foci are significantly associated with atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). However, we previously reported among patients with non-PV foci induced only once, none experienced AF recurrence. Thus, we aimed to investigate the correlation between the residual induction number of non-PV foci and ablation outcome in paroxysmal AF patients. We investigated 55 paroxysmal AF patients with residual non-PV foci after PVI and ablation of non-PV-foci. Study patients were classified into the residual one-time induction of non-PV foci (residual OTI-nPVF) group (n = 23) and residual repeatedly induced non-PV foci (residual RI-nPVF) group (n = 32). Furthermore, the residual RI-nPVF group was divided into the low inducibility group (n = 10) and high inducibility group (n = 22) according to the presence or absence of non-PV foci provoked by two sets of drug induction tests (non-PV foci inducibility). In addition, the latter was divided into the ablation group (n = 14) or observation group (n = 8). The 2-year AF recurrence-free rate in the residual RI-nPVF group was significantly lower compared to the residual OTI-nPVF group (53% vs. 90%, p = 0.018). There was no significant difference of the 2-year AF recurrence-free rates in the inducibility of non-PV foci (p = 0.913) and the presence or absence of ablation (p = 0.812) in the residual RI-nPVF group. Among paroxysmal AF patients, the presence of residual RI-nPVF was associated with higher AF recurrence compared to residual OTI-nPVF. Furthermore, within residual RI-nPVF subgroup, non-PV foci inducibility or ablation of some residual RI-nPVF did not affect ablation outcome.

Magnetic properties of the amorphous Co-Fe-Cr-Si-B alloy after annealing in unsaturated magnetic field

The regularities of influence of temperature and intensity of a longitudinal magnetic field significantly less than the saturation field during annealing on the magnetic properties of an amorphous soft magnetic alloy based on Co have been studied. The possibility of the effectiveness of such treatment in comparison with traditional annealing without a field due to partial or complete suppression of stabilization of domain boundaries because of directional ordering is demonstrated. Annealing at temperatures below the Curie point with the application of unsaturated field exceeding the saturation field of the residual induction of an amorphous alloy in as-quenched state (40 A/m) showed the greatest efficiency compared with annealing without a field in terms of simultaneously reducing the coercive force Hc and increasing the low-field permeability µ0.3 and maximum permeability µmax. In comparison with non-field annealing, depending on the conditions of unsaturated magnetic field annealing, the possibility of reducing Hc by 39 %, increasing µmax by 4.5 times and µ0.3 by 3.8 times is shown. After annealing in unsaturated field on the magnetization curve of the alloy Co69Fe3.7Cr3.8Si12.5B11, the perminvar region, as well as the parabolic region where Rayleigh's law is fulfilled, end in lower fields than after annealing without a field. The results obtained are discussed taking into account the occurrence of various physical processes in the alloy during heat treatment.

A Sensorless Heavy Load Starting Control Method For SRMs With Residual Inductance Calculation and Polynomial Fitting

A Sensorless Heavy Load Starting Control Method For SRMs With Residual Inductance Calculation and Polynomial Fitting

Effect of Field Annealing on Magnetic Properties of Magnetic Soft Iron–Germanium Alloys

Abstract—The concentration dependence of the magnetic properties of iron–germanium alloys before and after thermomagnetic treatment, which represents an annealing of alloy samples in the ferromagnetic state in a permanent or alternating magnetic field (magnetic field annealing – MFA), has been investigated. It is shown that before MFA, with an increase in the germanium content in the range of 3–30 at % Ge, the coercive force increases and the residual induction decreases. As a result of thermomagnetic treatment, in the alloy samples magnetic anisotropy is induced: the magnetic hysteresis loops become narrower, the residual induction increases, and the coercive force decreases. Thermomagnetic treatment is effective for Fe–Ge alloys with a germanium content from 6 to 18 at %, and its highest efficiency is observed at 12 at % Ge. Features of the structural state of iron–germanium alloys and their role in the formation of magnetic properties during annealing in a magnetic field are discussed.

Abstract B032: Outcomes of patients with acute promyelocytic leukemia treated at John Peter Smith Hospital

Abstract Background: Acute Promyelocytic Leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML), accounting for about 10% of all AML cases. Historically, APL was considered to be the subtype of AML with the worst prognosis because most newly diagnosed patients died within a few weeks, and only 35% to 45% of patients achieved long-term survival. The discovery and application of all trans retinoic acid (ATRA) improved complete remission (CR) rate and overall survival (OS) to 70%. Combination of ATRA, a vitamin A derivative, and arsenic trioxide (ATO) as induction therapy for APL resulted in 90-95% CR and >90% 5-year OS. Even though CR and OS has improved, early death (5%-10%) remains the most challenging issue for the disease, especially in resource poor settings. Since APL is rare, oncologists in community may not be fully equipped to treat early complications. John Peter Smith hospital (JPS) is a safety-net hospital serving the needs of underserved population in north Texas. We report outcomes of patients with APL treated at JPS. Methods: Data was obtained from the JPS Oncology Registry. Patients were diagnosed with APL from 1/1/2017 to 12/31/2020 with partial or complete treatment at JPS. We collected non-identifiable patient demographics, diagnosis and initial treatment and complication details. Remission documentation by disappearance of the chromosome abnormality, time from diagnosis to date of death (if applicable) or last activity in medical chart (any phone call with patient, office visit) before 6/12/2023 were obtained. Time to CR and any use of consolidation or maintenance treatment was also collected. Results: 8 APL patients were included- 3 were high-risk patients and 5 were low-risk. Half were male. Age ranged from 22 to 64 years. 5 were under the age of 40 years, 2 were in their 40s and 1 was in 60s at diagnosis. Hispanic:4, Black:3, Asian:1. Induction treatment included ATRA+ATO in 6 patients, while 2 high risk patients received ATRA plus anthracycline-based chemotherapy. Bone marrow morphology post induction was negative in all patients indicating CR (median time to CR was 41.5 days). During induction, treatment complications occurred in all patients including bleeding (75%), clotting (63%), neutropenic fever (50%). Differentiation syndrome (50%) and DIC (50%). All patients underwent ATRA+ATO consolidation treatment for 8-10 months. No patients relapsed. All patients were alive at the time of last medical chart entry (6/12/2023) without active cancer. Conclusions: All patients were in CR post induction treatment. 4 had minimal residual disease post induction. All patients received consolidation with ATRA+ATO, eventually there was no disease detected at molecular level. No patients relapsed. All patients were alive with no active disease at their last follow-up. Excellent outcomes in APL are possible at safety-net setting but will need diligent care to prevent, predict and treat early complications; this may require communication with academic leukemia specialists when transfer to leukemia treatment centers is not possible. Citation Format: Kavya Athipatla, Kari Teigen, Kalyani Narra. Outcomes of patients with acute promyelocytic leukemia treated at John Peter Smith Hospital [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B032.

Integrated analysis of randomized controlled trials evaluating bortezomib + lenalidomide + dexamethasone or bortezomib + thalidomide + dexamethasone induction in transplant-eligible newly diagnosed multiple myeloma.

Providing the most efficacious frontline treatment for newly diagnosed multiple myeloma (NDMM) is critical for patient outcomes. No direct comparisons have been made between bortezomib + lenalidomide + dexamethasone (VRD) and bortezomib + thalidomide + dexamethasone (VTD) induction regimens in transplant-eligible NDMM. An integrated analysis was performed using patient data from four trials meeting prespecified eligibility criteria: two using VRD (PETHEMA GEM2012 and IFM 2009) and two using VTD (PETHEMA GEM2005 and IFM 2013-04). The primary endpoint was met, with VRD demonstrating a noninferior rate of at least very good partial response (≥ VGPR) after induction vs VTD. GEM comparison demonstrated improvement in the ≥ VGPR rate after induction for VRD vs VTD (66.3% vs 51.2%; P = .00281) that increased after transplant (74.4% vs 53.5%). Undetectable minimal residual disease rates post induction (46.7% vs 34.9%) and post transplant (62.4% vs 47.3%) support the benefit of VRD vs VTD. Treatment-emergent adverse events leading to study and/or treatment discontinuation were less frequent with VRD (3%, GEM2012; 6%, IFM 2009) vs VTD (11%, IFM 2013-04). These results supported the benefit of VRD over VTD for induction in transplant-eligible patients with NDMM. The trials included are registered with ClinicalTrials.gov (NCT01916252, NCT01191060, NCT00461747, and NCT01971658).

Modelling and optimization of residual stress induction on laser-worked X12Cr turbine blades

The energy and power industry conventionally depends on large-scale turbomachinery to meet the ever-growing global energy demands. However, unplanned in-service failures remain a threat to sustainability with safety and economic consequences. The laser shock surface treatment technique is being considered a competitive alternative in mitigating crack initiation and growth, wear and fatigue of industrial components such as turbine blades. This paper presents the modelling and optimization of laser shock treatment parameters using numerical methods and commercial codes such as ABAQUS® and MATLAB®. Model-based process optimization parameters for the induction of global optimum compressive residual stress distribution in laser-worked Chromium-12 based high strength steel alloy (X12Cr) turbine blade is established, showing parametric combinations of inputs variables within the domain under investigation, yielding maximized CRS outputs. A hierarchy of significance of the input parameters to the laser shock peening process for stress induction has also been put forward as an outcome of this study. The capacity to predict and analyze outcomes before actual treatment of the components is beneficial and imperative to cutting costs, downtimes and other economic losses associated with unplanned failure of these components.

Intramuscular cabotegravir and rilpivirine concentrations after switching from efavirenz-containing regimen.

Intramuscular cabotegravir/rilpivirine (IM CAB/RPV) are metabolized by UGT1A1/CYP3A4. Efavirenz induces both enzymes; therefore, switching from an efavirenz-containing regimen to IM CAB/RPV could possibly result in suboptimal levels. Due to their long dosing interval, clinical studies with IM CAB/RPV are challenging. We used physiologically based pharmacokinetics (PBPK) modelling to simulate the switch from efavirenz to IM CAB/RPV. First, we developed the drug models and verified the performance of the PBPK model to predict the pharmacokinetics of IM cabotegravir, IM rilpivirine and efavirenz by comparing the simulations against observed clinical data. Second, we verified the ability of the model to predict the effect of residual induction with observed data for the switch from efavirenz to dolutegravir or rilpivirine. Finally, we generated a cohort of 100 virtual individuals (20-50 years, 50% female, 18.5-30 kg/m2 ) to simulate IM CAB/RPV concentrations after discontinuing efavirenz in extensive and slow metabolizers of efavirenz. IM CAB concentrations were predicted to decrease by 11% (95% confidence interval 7-15%), 13% (6-21%) and 8% (0-18%) at day 1, 7 and 14 after efavirenz discontinuation. CAB concentrations were predicted to remain above the minimal efficacy threshold (i.e., 664 ng/mL) throughout the switch period both in extensive and slow metabolizers of efavirenz. Similarly, IM RPV concentrations were modestly decreased with the lowest reduction being 10% (6-14%) on day 7 post last efavirenz dose. Our simulations indicate that switching from an efavirenz-containing regimen to IM CAB/RPV does not put at risk of having a time window with suboptimal drug levels.

INVESTIGATION OF MAGNETIC HYSTERESIS PROPERTIES OF ISOTROPIC MAGNETICALLY HARD ALLOYS OF THE Fe-Cr-Co SYSTEM ALLOYED WITH TUNGSTEN

Hard magnetic alloys Fe-30Cr-20Co (wt.%) alloyed with tungsten in an amount of up to 3 wt.% were obtained by powder metallurgy. A study of magnetic properties showed that tungsten additions increase the values of the coercivity Hc and the maximum energy product (BH)max, but at the same time reduce the residual induction Br. This effect increases with increasing tungsten content in the material. The maximum values of Hc (55.8 kA/m) and (BH)max (17.2 kJ/m3) are observed in the alloy alloyed with 3 wt.% W. At the same time, the alloys studied in the work turned out to be sensitive to thermal conditions processing. According to X-ray phase analysis, after a full processing cycle, alloys contain a noticeable proportion of non-magnetic ɣ-phase, but the magnetic properties correspond to the level of cast analogues. During compression tests, all samples of tungsten alloyed alloys failed before reaching a deformation rate of 20%, while the unalloyed Fe-30Cr-20Co (wt.%) alloy deformed without failure under these conditions. Thus, tungsten additives reduce the ductility of the material.

High burden of clinically significant adverse events associated with contemporary therapy for pediatric T-cell acute lymphoblastic leukemia/lymphoma.

Despite improvements in survival for children with T-cell acute lymphoblastic leukemia and lymphoma (T-ALL/LLy), morbidity remains high. However, data are lacking regarding comprehensive descriptions of clinically relevant adverse events (AEs) experienced during early intensive chemotherapy. This single-institution retrospective study evaluated children aged 1-21 years with T-ALL/T-LLy diagnosed from 2010 to 2020. Physician chart abstraction identified and graded 20 clinically relevant AEs. AE rates were analyzed by T-ALL or LLy, minimal residual disease status, induction steroid, and use of antimicrobial prophylaxis. Statistical comparisons used the Kruskal-Wallis test (continuous variables) and Chi-square or Fisher's exact test (categorical variables). The cohort included 120 patients (T-ALL: 88; T-LLy: 32). Most patients experienced AEs during induction (85 out of 120; 70.8%) and consolidation (89 out of 111; 80.2%). Nonsepsis infection was common in induction (26 out of 120; 21.7%) and consolidation (35 out of 111; 31.5%). Patients treated with dexamethasone during induction had significantly higher rates of nonsepsis infection and/or sepsis during consolidation than those who received prednisone (p<.01). Clinically significant AEs are extremely common during induction and consolidation therapy for patients with T-ALL/LLy. Infectious AEs are particularly prevalent. These results can inform conversations with patients and families and aid in the development of toxicity-related aims in the next generation of, prospective clinical trials in T-ALL/LLy.

Application of the parameters of the remagnetization curve`s spectral characteristics to determine the hardness of ferromagnetic material

The paper discusses the results of the practical application of the harmonic components obtained in the analysis of the magnetic hysteresis loop to determine the hardness of steel. The magnetic characteristics of steel, including the magnetic hysteresis loop, were determined using a DIUS-1.15M magnetic structureoscope. Using the group method of data handling by the value of odd harmonic components, a complex parameter was detected. The weighting coefficients of the influence of harmonic components on the value of the complex parameter were determined. By the example of considering the dependences of coercive force, residual induction and the complex parameter obtained by the method of group argument accounting on the Brinell hardness of the material, it is shown that the complex parameter can be used to determine the hardness with the smallest error.

Management of Drug Interactions with Inducers: Onset and Disappearance of Induction on Cytochrome P450 3A4 and Uridine Diphosphate Glucuronosyltransferase 1A1 Substrates.

People living with HIV may present co-morbidities requiring the initiation and subsequently the discontinuation of medications with inducing properties. The time to reach maximal enzyme induction and to return to baseline enzyme levels has not been thoroughly characterized. The aim of this study was to evaluate the onset and disappearance of dolutegravir [uridine diphosphate glucuronosyltransferase (UGT) 1A1 and cytochrome P450 (CYP) 3A4 substrate] and raltegravir (UGT1A1 substrate) induction with strong and moderate inducers using physiologicallybased pharmacokinetic (PBPK) modeling. The predictive performance of the PBPK model to simulate dolutegravir and raltegravir pharmacokinetics and to reproduce the strength of induction was verified using clinical drug-drug interaction studies (steady-state induction) and switch studies (residual induction). The model was considered verified when the predictions were within 2-fold of the observed data. One hundred virtual individuals (50% female) were generated to simulate the unstudied scenarios. The results were used to calculate the fold-change in CYP3A4 and UGT1A1 enzyme levels upon initiation and discontinuation of strong (rifampicin) or moderate (efavirenz or rifabutin) inducers. The time for reaching maximal induction and subsequent disappearance of CYP3A4 induction was 14 days for rifampicin and efavirenz but 7 days for rifabutin. The distinct timelines for the moderate inducers relate to their different half-lives and plasma concentrations. The induction and de-induction processes were more rapid for UGT1A1. Our simulations support the common practice of maintaining the adjusted dosage of a drug for another 2 weeks after stopping an inducer. Furthermore, our simulations suggest that an inducer should be administered for at least 14 days before conducting interaction studies to reach maximal induction.

Prediction of the concentration inhomogeneity of powder magnetic hard alloys based on the Fe-Cr-Co-Mo system and the effect of Sm additions on their magnetic properties

Hysteresis alloys based on Fe-Cr-Co system are extensively used in the instrument-making industry as a material for synchronous motors of navigation systems, in the electronic industry, and other mechanical engineering fields. The following requirements are imposed on Fe-Cr-Co alloys: temperature stability of magnetic characteristics over time, manufacturability, low porosity and concentration inhomogeneity, which allow to obtain high-quality magnetic and mechanical properties. Materials based on conventional alloying systems, such as Fe-Cr-Co, have outlived themselves. An urgent line of the development of new materials and improvement of the properties of existing ones is alloying with rare-earth metals. The effect produced by Sm addition on powder analogs of Fe-Cr-Co system remains unstudied. In this paper, 22Kh15K4MS powder magnetic hard alloy alloyed with samarium in an amount of 0.5 wt. % was studied. The billets were obtained by cold pressing at a pressure of 600 MPa followed by vacuum sintering. The concentration inhomogeneity of Cr, Co, Mo, Sm was determined after 12 different sintering modes. A model of diffusion homogenization of ridge alloys, which allows to numerically evaluate the effect of sintering modes on the concentration inhomogeneity, was plotted. The distributions of chromium, cobalt, and molybdenum correspond to the asymptotically logarithmically normal law. Samarium is unevenly distributed in the structure. The effect of samarium additions on the magnetic properties of the alloy has been demonstrated. The alloying of 22Kh15K4MS alloy with 0.5 wt. % of samarium allows to obtain powder hysteresis magnets with a coercive force in the range from 3.9 to 33.0 kA/m and a residual magnetic induction from 0.44 to 0.95 T.

Time-Limited Maintenance with Ibrutinib after First-Line Therapy and the Incremental Impact on Minimal Residual Disease (MRD) for Patients with Chronic Lymphocytic Leukemia (CLL)

Background: Inhibitors of Bruton's tyrosine kinase (BTKi) are approved and clinically used as indefinite treatments (until disease progression) irrespective of the depth of response in patients (pts) with CLL. Despite impressive, sustained efficacy, their ability (as single agent) to target residual disease clone post induction treatment in CLL is not well established. As indefinite treatment is associated not only with cumulative toxicity but also high cost and compromised quality of life, we investigated the benefit of time-limited maintenance treatment (3 years) with ibrutinib to assess the ability of a BTKi to further deepen antitumor response achieved post induction treatment. Methods: CLL pts (n=35) who had residual disease (by clinical or molecular assessment) after primary induction treatment were enrolled on a prospective phase 2 trial (NCT02649387). MRD assessed in blood (PB)/bone marrow (BM), was determined by 8-color flowcytometry (1x10-4) and defined as ≥1 CLL cell per 10,000 leukocytes or ≥0.01%. Patient were eligible if they had detectable residual (non-progressive) disease within 1 year of completing induction and no prior ibrutinib (or other BTKi) treatment. Ibrutinib 420mg PO QD was given on days 1-28 of a 28-day cycle for up to 36 cycles. Clinical (iwCLL 2008 response criteria) and molecule response MRD (on PB) was done at baseline and then every 3 cycles while on treatment. BM-MRD evaluation was conducted only if PB-MRD was negative (on two separate timepoints 3 months apart). Monitoring of the PB-MRD was continued for 24 months after completing time-limited maintenance with ibrutinib. Cumulative toxicity was assessed using the CTCAE v4.0 and iwCLL criteria. Results: Patient characteristics are summarized in Table 1. In 34 out of 35 (97%) patients, obinutuzumab alone was used as induction therapy. The median follow up is 38.6 months (range 0.9-73.2) and the median number of maintenance cycles completed is 34 (range 1-36). Of the 33 patients assessed for PB-MRD, 8 (24.2%) pts became MRD- on at one assessment. Five patients had BM-MRD assessment with 1 (2.8%) converting to MRD-. The median time to achievement of MRD- was 4.4 months (range 2.7-34.7). We noted that single agent ibrutinib was unable to deliver stringent MRD-negativity (defined as achievement of MRD- status both in PB and BM sustained over 2 consecutive evaluations at least 3 months apart).To assess if pre-maintenance response could impact MRD post-treatment; we note that out of the 8 pts that achieved MRD-, 2 (25%) started with CR and 6 (75%) with nPR/PR at registration. Deepening of response was noted in 5 pts (14.3%) after a median of 14 cycles [3 (8.6%) pts improved nPR to CR and 1(2.9%) went from nPR to CRi and 1 (2.9%) went from a CRi to a CR]. Nine patients proceeded to subsequent treatment with the median time to next treatment (mTTNT) of 32.5 m (range: 12.1 - 61.0). One patient died due to a failure to thrive and acute kidney injury on dialysis and six pts have progressed. The median PFS for the entire cohort was 41.1 m (95% CI: 39.8 - NE). The most commonly reported adverse events (AEs) (seen in >10% pts) regardless of attributions were thrombocytopenia (24 pts; 68.6%), anemia (12 pts; 34.3%), neutropenia (9 pts; 25.7%), lymphopenia (9 pts; 25.7%), hypertension (9 pts; 25.7%), leucopenia (6 pts; 17.1%), fatigue (5 pts; 14.3%), headache (4 pts; 11.4%), and skin infections (4 pts; 11.4%). Atrial fibrillation (AFib) was noted in 3 pts (8.6%). Conclusion: We conclude that BTK targeting with ibrutinib alone although able to clear PB-MRD (24.2%), had limited efficacy to eradicate BM-MRD (2.8%) demonstrating a differential impact in these two disease compartments. While the rate of complete MRD eradication was not necessarily high (when compared to recent data with BTKi/BCL2i combination regimens) MRD-kinetics over time demonstrated progressive decrease in disease burden and response improvement with maintenance treatment. The sequential single agent treatment approach was well tolerated, and the time-limited therapy aimed at minimizing cumulative toxicity seemed to be effective in lowering rate of Afib (compared to historical control ~16%). This data warrants further investigation of time-limited maintenance therapy with newer, more favorably tolerated BTKi and/or Bcl2i post induction treatment(s) to optimize response vs. cumulative toxicity. Further evaluation of sequential time-limited treatments in CLL is warranted. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

DEPENDENCE OF ELECTROMAGNETIC PARAMETERS OF PRODUCTS FROM STEEL 09G2S ON THEIR MECHANICAL PROPERTIES

"This work presents a method for a non-destructive method for determining the tensile strength, yield strength and relative elongation of steel products by identifying the relationship between mechanical and electromagnetic properties. Coercive force, maximum magnetic permeability and residual magnetic induction were chosen as electromagnetic properties, as the most structurally sensitive parameters to the composition and heat treatment of products. The difference of the work carried out is the use of several physical characteristics simultaneously as control parameters, since multi-parameter control methods provide higher information content and reliability of assessing the state of materials. The result of the research is a method for determining the relationship between mechanical and electromagnetic parameters. At the same time, the deviation of the values ​​obtained by this method and the actual values ​​during the tensile test does not exceed 5 %. The proposed method for determining the values ​​of mechanical properties can be used for any steel product and its grade, having previously established, for the corresponding composition of the material, the relationship between mechanical and electromagnetic properties. Keywords: coercive force, tensile strength, non-destructive testing, mathematical model, mechanical properties of steel."