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PURPOSE: We investigated the prevalence of financial toxicity in a population undergoing hematopoietic cell transplantation (HCT) evaluation and measured its impact on post-transplant clinical and health-related quality-of-life outcomes. MATERIALS AND METHODS: This was a prospective study in patients undergoing evaluation for allogeneic HCT between January 1, 2018, and September 23, 2020, at a large academic medical center. Financial health was measured via a baseline survey and the comprehensive score for financial toxicity-functional assessment of chronic illness therapy (COST-FACIT) survey. The cohort was divided into three groups: none (grade 0), mild (grade 1), and moderate-high financial toxicity (grades 2-3). Health-related quality of life outcomes were measured at multiple time points. Multivariate logistic regression analysis evaluated factors associated with financial toxicity. Kaplan-Meier curves and log-rank tests was used to evaluate overall survival (OS) and nonrelapse survival. RESULTS: Of 245 patients evaluated for transplant, 176 (71.8%) completed both questionnaires (median age was 57 years, 63.1% were male, 72.2% were White, and 39.2% had myelodysplastic syndrome, 38.1% leukemia, and 13.6% lymphoma). At initial evaluation, 83 (47.2%) patients reported no financial toxicity, 51 (29.0%) with mild, and 42 (23.9%) with moderate-high financial toxicity. Patients with financial toxicity reported significant cost-cutting behaviors, including reduced spending on food or clothing, using their savings, or not filling a prescription because of costs (P <.0001). Quality of life was lower in patients with moderate-high financial toxicity at 6 months (P =.0007) and 1 year (P =.0075) after transplant. Older age (>62; odds ratio [OR], 0.33 [95% CI, 0.13 to 0.79]; P =.04) and income ≥$60,000 in US dollars (USD) (OR, 0.17 [95% CI, 0.08 to 0.38]; P <.0001) were associated with lower odds of financial toxicity. No association was noted between financial toxicity and selection for transplant, OS, or nonrelapse mortality. CONCLUSION: Financial toxicity was highly correlated with patient-reported changes in compensatory behavior, with notable impact on patient quality of life after transplant. Prospective cohort study demonstrates a major impact of #FinancialToxicity in driving cost-cutting behaviors and worse quality of life in patients undergoing bone marrow transplant [ABSTRACT FROM AUTHOR]

Recent studies have revealed the possible association between serum cholesterol levels and hematologic malignancy (HM). However, limited information is available about how reproductive factors interact with this association. Therefore, we investigated the roles of serum cholesterol in the risk of HM according to the menopausal status. We finally identified 1,189,806 premenopausal and 1,621,604 postmenopausal women who underwent a national health screening program in 2009 using data from the Korean National Health Insurance Service database. Overall, 5449 (0.19%) developed HM. Among postmenopausal women, the inverse associations were observed between total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) levels, and the risk of overall HM. In premenopausal women, the highest quartile of HDL-C was associated with a reduced risk of HM compared with the lowest quartile of HDL-C consistent with results in postmenopausal women (adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] [0.68–0.95]), whereas the highest quartile of triglyceride (TG) showed an increased risk of HM compared to the lowest quartile of TG, (aHR 1.22, 95% CI [1.02,1.44]) only in premenopausal women. Our finding suggests that lipid profiles are differently associated with HM risk by menopausal status. [ABSTRACT FROM AUTHOR]

Allogeneic-HCT (allo-HCT), while potentially curative, can result in significant complications including graft versus host disease (GVHD). Prior studies suggest that metabolic syndrome may be one risk factor for GVHD. We hypothesized that hepatic steatosis on pre-HCT computed tomography (CT) scans may be a marker for development of GVHD and poor outcomes in allo-HCT. In this retrospective study, we reviewed the pre-HCT CT scans and transplant outcome data of patients who underwent allo-HCT at Duke University Medical Center from 2009 to 2017. The presence of steatosis was confirmed using CT attenuation measurements. We then assessed the association between pre-HCT hepatic steatosis and HCT-related outcomes including GVHD. 80 patients who had pre-HCT CT scans were included in the study. Pre-transplant hepatic steatosis was associated with the development of chronic GVHD (OR 4.2, p = 0.02), but was not associated with acute GVHD (OR 1.3, p = 0.7), non-relapse mortality (p = 0.81) or overall survival (p = 0.74). Based on this single center retrospective study, pre-transplant hepatic steatosis is associated with development of chronic GVHD. Further, prospective study with other imaging modalities including non-contrasted CT scans is needed to determine if this association is reproducible. [ABSTRACT FROM AUTHOR]

Although treatment outcomes of multiple myeloma patients have improved significantly during the last two decades, myeloma is still an incurable disease. There are newly emerging immunotherapies to treat multiple myeloma including monoclonal antibodies, antibody-drug conjugate, bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy. Impressive response rate and clinical efficacy in heavily pretreated myeloma patients led to the FDA approval of the first myeloma CAR-T therapy in March 2021. Among many different targets for myeloma CAR-T therapies, B Cell Maturation Antigen (BCMA) has been the most successful target so far, but other targets which can be used either for single-target or dual-target CAR-T's are actively being explored. Clinical efficacy and safety of current myeloma CAR-T therapies will be presented here. Potential mechanisms leading to resistance include clearance of CAR-T cells, antigenic escape, and immunosuppressive tumor microenvironment. Novel strategies to enhance myeloma CAR-T will also be described. In this article, we provide a comprehensive review of the current data and the future directions of myeloma CAR-T therapies. [ABSTRACT FROM AUTHOR]

Despite the growing interest in Alzheimer's disease, issues of ethnicity and culture associated with dementia are still under-studied. In this study, particular attention was given to Korean caregivers who seem to suffer the most in terms of family burdens and emotional distress. Content analysis was performed on 798 messages posted to online support groups for dementia caregivers. The results indicated that Korean caregivers expressed more family burden (“impact on finance” and “sense of entrapment”) than U.S. caregivers. Also, the Korean caregivers expressed more negative emotions than the U.S. caregivers, and consequently sought more emotional support from online support groups than the U.S. caregivers. [ABSTRACT FROM AUTHOR]

Simple Summary: The present nationwide population-based longitudinal cohort study showed that diabetes was associated with an increased risk of hematologic malignancies independent of obesity. The risk of NHL increased according to the progression of dysglycemia towards a longer diabetes duration, while HL did not. There have been conflicting results regarding the association between diabetes and the risk of hematologic malignancies, and its interaction with obesity is unknown. This study determined the risk of hematologic malignancies according to the glycemic status in a population-based study involving health screening 9,774,625 participants. The baseline glycemic status of the participants was categorized into no diabetes, impaired fasting glucose (IFG), newly detected diabetes, diabetes duration <5 years, and diabetes duration ≥5 year groups. The risks of overall and specific hematologic malignancies were estimated using a Cox regression analysis. During a median follow up of 7.3 years, 14,733 hematologic malignancies developed. The adjusted hazard ratio (aHR) for the risk of all the hematologic malignancies was 0.99 (95% confidence interval (CI) 0.95–1.02) for IFG, 0.99 (95% CI 0.91–1.08) for newly detected diabetes, 1.03 (95% CI 0.96–1.11) for diabetes duration <5 years, and 1.11 (95% CI 1.03, 1.20) for diabetes duration ≥5 year groups. The association was independent from obesity. The risk of non-Hodgkin's lymphoma (NHL) increased according to the progression of dysglycemia towards a longer diabetes duration, while Hodgkin's lymphoma did not. This study in Korea demonstrated diabetes to be associated with an increased risk of hematologic malignancies independent of obesity. The NHL risk increased with the diabetes duration. [ABSTRACT FROM AUTHOR]

Simple Summary: There is preclinical evidence that abnormalities in lipid metabolism promote cancer development, and a few studies show the association between lipid levels and multiple myeloma (MM). However, to our knowledge, the role of lipid variability as a risk factor for MM has not been evaluated. We investigated whether lipid level and its variability are associated with the development of MM at a population level. Lower baseline lipid levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides, and high variability in high-density lipoprotein cholesterol were all associated with increased risk of developing MM. These findings support the role of lipid metabolism in MM risk. (1) Background: There is evidence that abnormality in lipid metabolism promotes cancer development. This study investigated whether lipid level and its variability are associated with the development of MM at a population level. (2) Methods: A retrospective cohort study included a total of 3,527,776 subjects aged 40 and above who participated in ≥3 health examinations within the previous five years, including the index year (2012–2013). Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) were measured, and visit-to-visit lipid variability were calculated by variability independent of the mean (VIM) method. The study population was followed from the health examination date in the index year until the diagnosis of MM, death, or the last follow-up date (31 December 2017). (3) Results: During a median (5–95%) 5.1 years of follow-up, 969 subjects developed MM. A lower risk of MM was observed with higher quartiles of baseline lipid levels compared to the lowest quartile group (Q4 vs. Q1: adjusted hazard ratios (aHRs) 0.51, 95% confidence interval (CI) (0.42–0.61) for TC; 0.50 (0.41–0.61) for HDL-C; 0.65 (0.54–0.77) for LDL-C; and 0.72 (0.60–0.87) for TG in model (3). Among all lipid measures, only variability in HDL-C was associated with risk of MM: aHRs (95% CI) were 1.12 (0.91–1.38), 1.19 (0.97–1.46), and 1.34 (1.09–1.65) in the Q2, Q3, and Q4, respectively, compared to the Q1 of VIM of HDL-C. (4) Conclusions: This study shows that patients with lower lipid levels and high HDL-C variability are at increased risk of developing MM. [ABSTRACT FROM AUTHOR]

Purpose: While renal impairment is one of the first clinical manifestations of multiple myeloma (MM), declined renal function may conversely be a risk factor for cancers including MM. In this study, we investigated the relationship between chronic kidney disease and MM at a population level., Materials and Methods: A total of 9,809,376 adults who participated in a nationwide health screening program and had no MM, cancer or end-stage renal disease at baseline were investigated for incidence of MM. The impact of estimated glomerular filtration rate (eGFR) and random urine dipstick proteinuria, and interactive associations of the two factors on the MM incidence were evaluated., Results: The general incidence of MM was 4.8 per 100,000 person-years (mean follow-up of 8.3 years). Participants with eGFR < 60 mL/min/1.73 m2 (5.8% of participants) had higher MM incidence than those with eGFR ≥ 60 mL/min/1.73 m2 (adjusted hazard ratio, 1.29; 95% confidence interval, 1.17 to 1.43). When eGFR was graded into five levels, there was a significant inverse dose-response relationship between eGFR level and MM incidence at the lower eGFR levels (reference: eGFR 60-89 mL/min/1.73 m2). A dose-response relationship was also found with degree of dipstick proteinuria and incidence of MM., Conclusion: Adults with decreased renal function indicated either by decreased eGFR or presence of proteinuria are at a higher risk of developing MM compared to those without, and there is a dose-response relationship between the severity of renal impairment and MM incidence.

Background: Among the potential modifiable risk factors, the association between alcohol consumption and the risk of multiple myeloma remains controversial. We investigated the effects of weekly average alcohol consumption and drinking pattern on the risk of multiple myeloma using a nationwide representative database., Methods: We identified 11,737,467 subjects who participated in the Korean National Health Screening Program in 2009 and 2010. Cox regression analyses were performed to calculate the risk of multiple myeloma according to weekly alcohol consumption, drinking frequency, and amount per session., Results: During a mean follow-up period of 6.8 years after a one-year time lag, 6,981 subjects (3,921 men and 3,060 women) were diagnosed with multiple myeloma. Compared with nondrinkers, all drinkers were at a significantly lower risk for multiple myeloma. The risk of multiple myeloma was reduced in a dose-dependent manner: mild drinkers [adjusted HR (aHR), 0.89; 95% confidence interval (CI), 0.84-0.95], moderate drinkers (aHR, 0.83; 95% CI, 0.76-0.91), and heavy drinkers (aHR, 0.76; 95% CI, 0.69-0.85). Furthermore, both drinking frequency and amount per drinking session showed inverse association with the risk of multiple myeloma., Conclusions: Our large population-based study suggested an inverse dose-dependent association between total average alcohol consumption and the risk of multiple myeloma, and drinking frequency and amount per drinking session seemed to not differ in their relative contribution to the risk of multiple myeloma., Impact: On the basis of the unprecedentedly large number of study population analyzed in this study, our study provides solid epidemiologic evidence of alcohol consumption on multiple myeloma risk., (©2021 American Association for Cancer Research.)

Background: Anaplastic multiple myeloma (AMM) is a very rare but distinct subtype of multiple myeloma (MM) with an extremely poor prognosis. Due to its rarity, AMM lacks detailed descriptions and clear definitions. Moreover, there is no consensus on the treatment and evidence suggests that AMM responds poorly to several novel therapies. We conducted a literature review and retrospective case series to determine clinical characteristics, pathological features, and outcomes of AMM., Case Presentation: Published case reports and case series of AMM since 1983 were systematically extracted and reviewed. A total of 52 patients with AMM were reported in the PUBMED since 1983, including 26 males (50%) and 26 females (50%). The age ranged from 29 years old to 85 years old, with a mean age of 57.02 years old. Most of the patients presented with bone pain (23, 44.2%), fatigue (18, 34.6%), plasmacytoma (18, 34.6%) and weight loss (7, 13.5%). The median survival of the patients was 4 months. To investigate the outcomes of patients with AMM in the current era of treatment, a series of 14 patients with AMM diagnosed at our institute between December 2012 and July 2021was retrospectively analyzed. Our retrospective case series consisted of 12 males (85.7%) and 2 females (14.3%), with a mean age of 59 years old. Most of our AMM patients displayed bone lytic lesions as a common manifestation. The common cytogenetic abnormality was 1q amplification. All patients received standard combination chemotherapy consisting of proteasome inhibitors and/or immunomodulatory agents, and half of the patients underwent autologous hematopoietic stem cell transplantation. The median progression-free survival (PFS) and overall survival (OS) for our 14 AMM patients were 0.84 years and 1.52 years, respectively, which was significantly worse than the regular MM patients treated at our institute from 2003-2013 who had a PFS of 2.28 years and OS of 4.92 years., Conclusions: AMM is a very rare, morphologically distinct variant of MM. It has adverse cytogenetics and an aggressive course. It is often resistant to standard chemotherapy and presents with an extremely low survival rate.

Background: Allogeneic hematopoietic stem cell transplantation (HCT) is an often curative intent treatment, however it is associated with significant gastrointestinal (GI) toxicity and treatment related mortality. Graft-versus-host disease is a significant contributor to transplant-related mortality. We performed a phase 2 trial of the somatostatin analog pasireotide to prevent gastrointestinal toxicity and GVHD after myeloablative allogeneic HCT., Methods: Patients received 0.9mg pasireotide every 12 hours from the day prior to conditioning through day +4 after HCT (or a maximum of 14 days). The primary outcomes were grade 3-4 gastrointestinal toxicity through day 30 and acute GVHD. Secondary outcomes were chronic GVHD, overall survival and relapse free survival at one year. Stool and blood samples were collected from before and after HCT for analyses of stool microbiome, local inflammatory markers, and systemic inflammatory and metabolic markers. Results were compared with matched controls., Results: Twenty-six patients received pasireotide and were compared to 52 matched contemporaneous controls using a 1-2 match. Grade 3-4 GI toxicity occurred in 21 (81%) patients who received pasireotide and 35 (67%) controls (p = 0.33). Acute GVHD occurred in 15 (58%) patients in the pasireotide group and 28 (54%) controls (p = 0.94). Chronic GVHD occurred in 16 patients in the pasireotide group (64%) versus 22 patients in the control group (42%) (p = 0.12). Overall survival at 1 year in the pasireotide group was 63% (95% CI: 47%,86%) versus 82% (95% CI: 72%, 93%) in controls (log-rank p = 0.006). Relapse-free survival rate at one year was 40% (95% CI: 25%, 65%) in the pasireotide group versus 78% (95% CI: 68%, 91%) in controls (log-rank p = 0.002). After controlling for the effect of relevant covariates, patients in the pasireotide group had attenuated post-HCT loss of microbial diversity. Analysis of systemic inflammatory markers and metabolomics demonstrated feasibility of such analyses in patients undergoing allogeneic HCT. Baseline level and pre-to-post transplant changes in several inflammatory markers (including MIP1a, MIP1b, TNFa, IL8Pro, and IL6) correlated with likelihood of survival., Conclusions: Pasireotide did not prevent gastrointestinal toxicity or acute GVHD compared to contemporaneous controls. Pasireotide was associated with numerically higher chronic GVHD and significantly decreased OS and RFS compared to contemporaneous controls. Pasireotide may provide a locally protective effect in the stool microbiome and in local inflammation as measured by stool calprotectin, stool beta-defensin, and stool diversity index., Competing Interests: Additional funding for this study was received from Novartis. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

NK cells become functionally competent to be triggered by their activation receptors through the interaction of NK cell inhibitory receptors with their cognate self-MHC ligands, an MHC-dependent educational process termed "licensing." For example, Ly49A(+) NK cells become licensed by the interaction of the Ly49A inhibitory receptor with its MHC class I ligand, H2D(d), whereas Ly49C(+) NK cells are licensed by H2K(b). Structural studies indicate that the Ly49A inhibitory receptor may interact with two sites, termed site 1 and site 2, on its H2D(d) ligand. Site 2 encompasses the α1/α2/α3 domains of the H2D(d) H chain and β(2)-microglobulin (β2m) and is the functional binding site for Ly49A in effector inhibition. Ly49C functionally interacts with a similar site in H2K(b). However, it is currently unknown whether this same site is involved in Ly49A- or Ly49C-dependent licensing. In this study, we produced transgenic C57BL/6 mice expressing wild-type or site 2 mutant H2D(d) molecules and studied whether Ly49A(+) NK cells are licensed. We also investigated Ly49A- and Ly49C-dependent NK licensing in murine β2m-deficient mice that are transgenic for human β2m, which has species-specific amino acid substitutions in β2m. Our data from these transgenic mice indicate that site 2 on self-MHC is critical for Ly49A- and Ly49C-dependent NK cell licensing. Thus, NK cell licensing through Ly49 involves specific interactions with its MHC ligand that are similar to those involved in effector inhibition.