Search

Multiple myeloma (MM) is twice as common in Black individuals compared with in White individuals, and diabetes mellitus (DM) disproportionately affects Black patients. Although numerous studies have shown a correlation between DM and MM, this has not been studied in the context of race and in vivo mechanisms. We conducted a retrospective clinical study of 5383 patients with MM of which 15% had DM (White, 12% and Black, 25%). Multivariable Cox models showed reduced overall survival (OS) for patients with DM (hazard ratio, 1.27; 95% confidence interval, 1.11-1.47; P < .001). This appeared to be driven by a marked difference in OS between White patients with and without DM but not in Black patients. In contrast, obesity was associated with better OS in Black patients but not in White patients. To complement this analysis, we assessed MM growth in a genetically engineered immunocompromised nonobese diabetic (Rag1-/-/muscle creatinine kinase promoter expression of a human IGF1R [M] with a lysine [K] to arginine [R] point mutation) mouse model to evaluate the mechanisms linking DM and MM. MM.1S xenografts grew in more Rag1-/-/MKR mice and grew more rapidly in the Rag1-/-/MKR mice compared with in controls. Western blot analysis found that MM1.S xenografts from Rag1-/-/MKR mice had higher phosphorylated S6 ribosomal protein (Ser235/236) levels, indicating greater activation of the mammalian target of rapamycin pathway. Our study is, to our knowledge, the first to evaluate racial differences in DM prevalence and survival in MM, as well as the effect of DM on tumor growth in mouse models. Our results suggest that DM may contribute to the higher incidence of MM in Black patients; and to improve survival in MM, DM management cannot be ignored.

Adult T-cell leukemia/lymphoma (ATLL) remains challenging to treat and has dismal outcome. Allogeneic stem-cell transplantation (allo-SCT) has promising results, but data remain scarce. In this single-center retrospective analysis of 100 patients with ATLL from north America (67 acute, 22 lymphomatous), 17 underwent allo-SCT and 5 autologous SCT (ASCT), with a median follow-up of 65 months. Post-transplant 3-years relapse incidence (RI) and non-relapse mortality (NRM) were 51% and 37%, respectively, and 3-year progression-free survival (PFS) and overall survival (OS) were 31% and 35%, respectively. ASCT 1-year RI was 80% compared to 30% in allo-SCT (p = 0.03). After adjusting for immortal-time bias, allo-SCT had significantly improved OS (HR = 0.4, p = 0.01). In exploratory multivariate analysis, patients achieving first complete response and Karnofsky score ≥ 90 had significantly better outcomes, as did Black patients, compared to Hispanics, who had worse outcome. In transplanted patients, 14 died within 2 years, 4 of which ASCT recipients. Our data are the largest ATLL transplant cohort presented to date outside of Japan and Europe. We show that allo-SCT, but not ASCT, is a valid option in select ATLL patients, and can induce long term survival, with 40% of patients alive after more than 5 years.

Research suggests that perspective-taking in children is associated with greater cognitive and emotion understanding as well as parent use of mental state language—words concerning inner mental states or feelings. However, prior research shows conflicting results on which categories of mental state language—cognition (e.g., think, know), emotion (e.g., happy), or desire (e.g., want)—facilitate children’s perspective-taking. The current study examines the relationship between parent mental state language and children’s perspective-taking.We are coding parent mental state language categories from a wordless book task with two-year-old children and assessing children’s perspective-taking using a card task (Flavell et al., 1981). Preliminary results (N=19, planned 41) show that, on average, parents use more cognition words per session than desire words and, on average, children score at chance on the perspective-taking task. Differences between mental state categories on children’s perspective-taking skills as well as individual variability will be analyzed.

PurposeSustained minimal residual disease (MRD) negativity is associated with long-term survival in multiple myeloma. The gut microbiome is affected by diet, and in turn can modulate host immunity, for example through production of short-chain fatty acids including butyrate. We hypothesized that dietary factors affect the microbiome (abundance of butyrate-producing bacteria or stool butyrate concentration) and may be associated with multiple myeloma outcomes.Experimental designWe examined the relationship of dietary factors (via a food frequency questionnaire), stool metabolites (via gas chromatography-mass spectrometry), and the stool microbiome (via 16S sequencing - α-diversity and relative abundance of butyrate-producing bacteria) with sustained MRD negativity (via flow cytometry at two timepoints 1 year apart) in myeloma patients on lenalidomide maintenance. The Healthy Eating Index 2015 score and flavonoid nutrient values were calculated from the food frequency questionnaire. The Wilcoxon rank sum test was used to evaluate associations with two-sided P < 0.05 considered significant.ResultsAt 3 months, higher stool butyrate concentration (P = 0.037), butyrate producers (P = 0.025), and α-diversity (P = 0.0035) were associated with sustained MRD negativity. Healthier dietary proteins, (from seafood and plants), correlated with butyrate at 3 months (P = 0.009) and sustained MRD negativity (P = 0.05). Consumption of dietary flavonoids, plant nutrients with antioxidant effects, correlated with stool butyrate concentration (anthocyanidins P = 0.01, flavones P = 0.01, and flavanols P = 0.02).ConclusionsThis is the first study to demonstrate an association between a plant-based dietary pattern, stool butyrate production, and sustained MRD negativity in multiple myeloma, providing rationale to evaluate a prospective dietary intervention.

[This corrects the article DOI: 10.1158/2643-3230.BCD-20-0102.].

UNLABELLED: Patients with multiple myeloma have a compromised immune system, due to both the disease and antimyeloma therapies, and may therefore be particularly susceptible to COVID-19. Here, we report outcomes and risk factors for serious disease in patients with multiple myeloma treated at five large academic centers in New York City in the spring of 2020, during which it was a global epicenter of the SARS-CoV-2 pandemic. Of 100 patients with multiple myeloma (male 58%; median age 68) diagnosed with COVID-19, 75 were admitted; of these, 13 patients (17%) were placed on invasive mechanical ventilation, and 22 patients (29%) expired. Of the 25 nonadmitted patients, 4 were asymptomatic. There was a higher risk of adverse outcome (intensive care unit admission, mechanical ventilation, or death) in Hispanics/Latinos (n = 21), OR = 4.7 (95% confidence interval, 1.3-16.7), and African American Blacks (n = 33), OR = 3.5 (1.1-11.5), as compared with White patients (n = 36). Patients who met the adverse combined endpoint had overall higher levels of inflammatory markers and cytokine activation. None of the other studied risk factors were significantly associated (P > 0.05) with adverse outcome: hypertension (n = 56), OR = 2.2 (0.9-5.4); diabetes (n = 18), OR = 0.9 (0.3-2.9); age >65 years (n = 63), OR = 1.8 (0.7-4.6); high-dose melphalan with autologous stem cell transplant

This article discusses a study on the use of colesevelam, a bile acid binder, for the treatment of lenalidomide-associated diarrhea in patients with multiple myeloma. The study found that colesevelam was highly effective in improving diarrhea symptoms, with minimal adverse events and no impact on the concentration of lenalidomide in the patients' bodies. The findings suggest that colesevelam can be a viable treatment option for lenalidomide-associated diarrhea in multiple myeloma patients, allowing them to continue benefiting from lenalidomide treatment. [Extracted from the article]

The rapid fouling and bacterial contamination of equipment, heat exchangers, and pipelines are major concerns in food manufacturing plants. The process of cleaning‐in‐place (CIP) in the food manufacturing industry involves hazardous chemicals such as sulfuric acid, chlorine, sodium hydroxide, and potassium hydroxide. This study aims to investigate the cleaning efficiency of a novel environment‐friendly solution, plasma‐activated water (PAW), for removing dairy and plant‐based fouling and for biofilm reduction. PAW was produced by exposing water to plasma, which is a partially ionized gas generated by applying electricity to air. PAW prepared in this study had a pH, electrical conductivity (EC), and oxidation–reduction potential (ORP) of 2.5 ± 0.1, 1170. 1 ± 202.2 μS/cm, and 589.0 ± 2.4 mV, respectively. Holding PAW at different temperatures (20–75°C) did not change pH, ORP, and EC significantly, while nitrite and nitrate concentrations in PAW did not show a consistent trend with temperature. The treatment time and temperature of PAW were optimized for cleaning fouled coupons (stainless‐steel type 304 and 316) using model fouling fluids (MFF) with dairy (whey) and plant‐based (oat) proteins using full‐factorial design. The optimized PAW combinations (15 min/75°C and 5 min/75°C) were found to be as effective for fouling removal as compared to CIP controls (conventional caustic and acid solutions). Optimized PAW also showed significant biofilm reduction of Listeria innocua on stainless‐steel coupons with/without fouling, with at least 4.4 log and 4.0 log reductions in L. innocua biofilms when attached to MFF‐whey and MFF‐oat, respectively. Practical applications: Plasma‐activated water (PAW) can inactivate a wide spectrum of microorganisms on various food and food contact surfaces. We propose the use of environment‐friendly plasma‐activated water (PAW), which can be prepared on‐site and on‐demand for cleaning‐in‐place (CIP) operations in the food industry. The results of this study suggest the potential of PAW as a promising CIP alternative for cleaning and sanitizing surfaces soiled by fouling deposits in dairy and plant‐based industries. [ABSTRACT FROM AUTHOR]

B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively). Comparing T-cell redirecting therapies, the incidence rate of severe infections was significantly lower with CAR-T compared to BsAb at 1-year (incidence-rate-ratio [IRR] = 0.43, 95%CI 0.25−0.76, P = 0.004). During periods of treatment-emergent hypogammaglobulinemia, BsAb recipients had higher infection rates (IRR:2.27, 1.31−3.98, P = 0.004) and time to severe infection (HR 2.04, 1.05–3.96, P = 0.036) than their CAR-T counterparts. During periods of non-neutropenia, CAR-T recipients had a lower risk (HR 0.44, 95%CI 0.21−0.93, P = 0.032) and incidence rate (IRR:0.32, 95% 0.17–0.59, P < 0.001) of severe infections than BsAb. In conclusion, we observed an overall higher and more persistent risk of severe infections with BsAb. Our results also suggest a higher infection risk during periods of hypogammaglobulinemia with BsAb, and with neutropenia in CAR-T recipients. [ABSTRACT FROM AUTHOR]