Rate of respiratory symptoms in naïve patients with Chronic lymphocytic leukemia

Objective: to evaluate the rate of respiratory symptoms (RS) in patients (pts) with Chronic Lymphocytic Leukemia (CLL) and its dependence on anemia, ischemic heart disease (IHD), respiratory diseases, smoking status.Materials and Methods: Retrospective analysis of medical records of pts’ with confirmed CLL who did not receive any treatment. RS (dyspnea, cough, sputum), comorbidity, smoking status were assessed. Parametric and nonparametric statistics were used for the results analysis.Results: 264 medical records of the pts with CLL who were hospitalized to Dnipro City Hematology Department in 2018 were evaluated. 46 medical records were included on final analysis (35 (76 %) men, age 64.0 (57.0;69.0) years). 8 (17.4%) of pts had dyspnea, 2 (4.3%) – dyspnea and cough, no one had sputum, 36 (78.3%) pts had no RS. According to presence of respiratory symptoms we divided the pts in two groups. Connection of respiratory symptoms with comorbidities and smoking status is present in table.

Radiological Findings on Chest Computed Tomography in Patients With the Primary Diagnosed Chronic Lymphoproliferative Diseases

Introduction The presence of concomitant respiratory pathology complicates the process of treatment and recovery of patients with chronic lymphoproliferative diseases (CLDs). Therefore, the diagnosis of lung injury is an important step in the management of such patients. Objectives The aim of this study was to determine the prevalence, nature, extent, and location of changes diagnosed by high-resolution chest computed tomography (CT) in patients with CLDs at the initial examination. Methods Medical records of inpatients who were hospitalized in 2018-2019 to the City Hematology Center of the Public Non-Profit Enterprise “City Clinical Hospital #4” of Dnipro City Council with a confirmed clinical diagnosis of CLDs were included in the retrospective study. The results of initial high-resolution chest CT were studied and analyzed. Results Out of 1,004 hospitalized patients with confirmed CLDs, 119 patients were primarily diagnosed. Among them, 81 patients underwent chest CT examination (68.1%) before the beginning of specific therapy. The average age was 65 (56;68) years, 46 (56.8%) were men. 23 (28.4%) patients were diagnosed with chronic lymphocytic leukemia, 28 (34.6%) patients with multiple myeloma, 24 (29.6%) patients with lymphoma, and six patients (7.4%) had other CLDs. It was found that both central and peripheral lymphadenopathy had about a third of the studied cohort of patients (33.3 and 29.6%, respectively), and these symptoms dominated in patients with chronic lymphocytic leukemia (43.5 and 50%, respectively), lymphoma (50 and 52.2%, respectively), and other CLDs (45.8 and 16.7%, respectively), in contrast to patients with multiple myeloma (7.1 and 0%, respectively). Lesions of the lung parenchyma were found in 45.7% of the studied cohort and were met more often in patients with multiple myeloma (67.9%). However, when comparing the prevalence of their categories, no statistically significant differences were found. Predictable bonedestructive changes were statistically significantly more common in patients with multiple myeloma than in other groups of patients with CLDs (P=0.0003). Conclusions Signs of pulmonary diseases during initial chest CT were found almost in half of the patients with CLDs. It potentially may affect the frequency of treatment complications in such patients. Lymphadenopathy was the most common finding on chest CT, especially in patients with chronic lymphocytic leukemia and lymphoma. And enlarged intrathoracic lymph nodes possibly could lead to pulmonary functions disorders. Among the types of lung parenchyma lesions, pneumofibrosis and foci of consolidation in the lower lung lobes were the most often diagnosed. Chest CT is informative at the stage of the initial examination of patients with CLDs not only for clinical diagnosis but also for the diagnosis of respiratory comorbidities and prediction of the disease outcome and treatment complications

Дослідження переробки нікель-кобальтвмісних металургійних відходів екологічно безпечним способом водневого відновлення

We studied kinetic patterns of hydrogen reduction of the scale of a nickel-cobalt containing precision alloy at a temperature of 673‒1573 K over a period from 0 to 180 minutes. The highest degree of reduction was achieved after thermal treatment at 1273 K – 99 %. This is predetermined by the intensification of reduction processes and a sufficient level of porosity, which ensures satisfactory gas exchange. It was discovered that the starting scale consists mainly of Fe3O4, Fe2O3 and FeO with atoms substituting their alloying elements. The target product of metallization had a sponge-like microstructure and consisted mainly of the solid solution of Co and Ni atoms in γ-Fe and the residual non-reduced Fe3O4 and FeO. The resulting phases had no noticeable susceptibility to sublimation.This has ensured a reduction in the losses of alloying elements while receiving and using the highly-alloyed metallized scale, which was confirmed by experimental- industrial tests. At the same time, recycling of industrial wastes contributes to a reduction in the technogenic intensity of industrial regions and improves ecological safety of the environmentИсследована кинетика водородного восстановления окалины никель-кобальтсодержащего прецизионного сплава. Целевой продукт металлизации после восстановления при 1273 K имел губчатую микроструктуру, преимущественно состоял из твердого раствора атомов Ni и Co в γ–Fe. Также выявлен остаток Fe3O4 и FeO. Опытно-промышленные испытания подтвердили эффективность использования новой легирующей добавки с параллельной утилизацией техногенных отходовДослідженно кінетику водневого відновлення окалини нікель-кобальтвмісного прецизійного сплаву. Цільовий продукт металізації після відновлення при 1273 K мав губчасту мікроструктуру, переважно складався з твердого розчину атомів Ni та Co в γ–Fe. Також виявлено залишок Fe3O4 та FeO. Дослідно-промислові випробування підтвердили ефективність використання нової легуючої добавки з паралельною утилізацією техногенних відході

Research Into Recycling of Nickel­cobalt­containing Metallurgical Wastes by the Ecologically­safe Technique of Hydrogen Reduction

We studied kinetic patterns of hydrogen reduction of the scale of a nickel-cobalt containing precision alloy at a temperature of 673‒1573 K over a period from 0 to 180 minutes. The highest degree of reduction was achieved after thermal treatment at 1273 K – 99 %. This is predetermined by the intensification of reduction processes and a sufficient level of porosity, which ensures satisfactory gas exchange. It was discovered that the starting scale consists mainly of Fe3O4, Fe2O3 and FeO with atoms substituting their alloying elements. The target product of metallization had a sponge-like microstructure and consisted mainly of the solid solution of Co and Ni atoms in γ-Fe and the residual non-reduced Fe3O4 and FeO. The resulting phases had no noticeable susceptibility to sublimation.This has ensured a reduction in the losses of alloying elements while receiving and using the highly-alloyed metallized scale, which was confirmed by experimental- industrial tests. At the same time, recycling of industrial wastes contributes to a reduction in the technogenic intensity of industrial regions and improves ecological safety of the environmen

Efficacy and safety of melflufen plus daratumumab and dexamethasone in relapsed/refractory multiple myeloma : results from the randomized, open-label, phase III LIGHTHOUSE study

Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone was approved in Europe for use in patients with triple-class refractory relapsed/refractory multiple myeloma (RRMM) with ≥3 prior lines of therapy and without prior autologous stem cell transplantation (ASCT) or with a time to progression >36 months after prior ASCT. The randomized LIGHTHOUSE study (NCT04649060) assessed melflufen plus daratumumab and dexamethasone (melflufen group) versus daratumumab in patients with RRMM with disease refractory to an immunomodulatory agent and a proteasome inhibitor or who had received ≥3 prior lines of therapy including an immunomodulatory agent and a proteasome inhibitor. A partial clinical hold issued by the US Food and Drug Administration for all melflufen studies led to financial constraints and premature study closure on February 23rd 2022 (data cut-off date). In total, 54 of 240 planned patients were randomized (melflufen group, N=27; daratumumab group, N=27). Median progression-free survival (PFS) was not reached in the melflufen group versus 4.9 months in the daratumumab group (Hazard Ratio: 0.18 [95% Confidence Interval, 0.05-0.65]; P=0.0032) at a median follow-up time of 7.1 and 6.6 months, respectively. Overall response rate (ORR) was 59% in the melflufen group versus 30% in the daratumumab group (P=0.0300). The most common grade ≥3 treatment-emergent adverse events in the melflufen group versus daratumumab group were neutropenia (50% vs. 12%), thrombocytopenia (50% vs. 8%), and anemia (32% vs. 19%). Melflufen plus daratumumab and dexamethasone demonstrated superior PFS and ORR versus daratumumab in RRMM and a safety profile comparable to previously published melflufen studies

Acalabrutinib versus investigator's choice in relapsed/refractory chronic lymphocytic leukemia : final ASCEND trial results

Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for patients with chronic lymphocytic leukemia (CLL). ASCEND is the pivotal phase 3 study of acalabrutinib versus investigator’s choice of idelalisib plus rituximab (IdR) or bendamustine plus rituximab (BR) in patients with relapsed/refractory (R/R) CLL. In the primary ASCEND analysis (median 16.1-month follow-up), acalabrutinib showed superior efficacy with an acceptable tolerability profile versus IdR/BR; here, we report final ~4 year follow-up results. Patients with R/R CLL received oral acalabrutinib 100 mg twice daily until progression or unacceptable toxicity, or investigator’s choice of IdR or BR. A total of 310 patients (acalabrutinib, n = 155; IdR, n = 119; BR, n = 36) were enrolled. At median follow-up of 46.5 months (acalabrutinib) and 45.3 months (IdR/BR), acalabrutinib significantly prolonged investigator-assessed progression-free survival (PFS) versus IdR/BR (median, not reached [NR] vs 16.8 months; P < 0.001); 42-month PFS rates were 62% (acalabrutinib) versus 19% (IdR/BR). Median overall survival (OS) was NR (both arms); 42-month OS rates were 78% (acalabrutinib) versus 65% (IdR/BR). Adverse events led to drug discontinuation in 23%, 67%, and 17% of patients in the acalabrutinib, IdR, and BR arms, respectively. Events of clinical interest (acalabrutinib vs IdR/BR) included all-grade atrial fibrillation/flutter (8% vs 3%), all-grade hypertension (8% vs 5%), all-grade major hemorrhage (3% vs 3%), grade ≥3 infections (29% vs 29%), and second primary malignancies excluding nonmelanoma skin cancer (7% vs 2%). At ~4 years follow-up, acalabrutinib maintained favorable efficacy versus standard-of-care regimens and a consistent tolerability profile in patients with R/R CLL

Health-related quality of life in patients with newly diagnosed multiple myeloma ineligible for stem cell transplantation: results from the randomized phase III ALCYONE trial

BackgroundIn the phase III ALCYONE trial, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) significantly improved overall response rate and progression-free status compared with VMP alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). Here, we present patient-reported outcomes (PROs) from ALCYONE.MethodsThe European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and EuroQol 5-dimensional descriptive system (EQ-5D-5L) questionnaire were administered at baseline, every 3months (year 1) and every 6months (until progression). Treatment effects were assessed using a repeated-measures, mixed-effects model.ResultsCompliance with PRO assessments was comparable at baseline (&gt;90%) and throughout study (&gt;76%) for both treatment groups. Improvements from baseline were observed in both groups for EORTC QLQ-C30 Global Health Status (GHS), most functional scales, symptom scales and EQ-5D-5L visual analog scale (VAS). Between-group differences were significant for GHS (p =0.0240) and VAS (p =0.0160) at month 3. Improvements in pain were clinically meaningful in both groups at all assessment time points. Cognitive function declined in both groups, but the magnitude of the decline was not clinically meaningful.ConclusionsPatients with transplant-ineligible NDMM demonstrated early and continuous improvements in health-related quality of life, including improvements in functioning and symptoms, following treatment with D-VMP or VMP.Trial registrationClinicalTrials.gov identifier NCT02195479, registered September 21, 201

Selinexor, bortezomib, and dexamethasone versus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by cytogenetic risk

In the phase 3 BOSTON study, patients with multiple myeloma (MM) after 1–3 prior regimens were randomized to once‐weekly selinexor (an oral inhibitor of exportin 1 [XPO1]) plus bortezomib‐dexamethasone (XVd) or twice‐weekly bortezomib‐dexamethasone (Vd). Compared with Vd, XVd was associated with significant improvements in median progression‐free survival (PFS), overall response rate (ORR), and lower rates of peripheral neuropathy, with trends in overall survival (OS) favoring XVd. In BOSTON, 141 (35.1%) patients had MM with high‐risk (presence of del[17p], t[4;14], t[14;16], or ≥4 copies of amp1q21) cytogenetics (XVd, n = 70; Vd, n = 71), and 261 (64.9%) exhibited standard‐risk cytogenetics (XVd, n = 125; Vd, n = 136). Among patients with high‐risk MM, median PFS was 12.91 months for XVd and 8.61 months for Vd (HR, 0.73 [95% CI, (0.4673, 1.1406)], p = 0.082), and ORRs were 78.6% and 57.7%, respectively (OR 2.68; p = 0.004). In the standard‐risk subgroup, median PFS was 16.62 months for XVd and 9.46 months for Vd (HR 0.61; p = 0.004), and ORRs were 75.2% and 64.7%, respectively (OR 1.65; p = 0.033). The safety profiles of XVd and Vd in both subgroups were consistent with the overall population. These data suggest that selinexor can confer benefits to patients with MM regardless of cytogenetic risk. ClinicalTrials.gov identifier: NCT03110562