Pre-Diagnosis Dietary Patterns and Risk of Multiple Myeloma in the NIH-AARP Diet and Health Study.

Background: Despite patient interest in knowing whether diet is linked to multiple myeloma (MM), there is limited research on dietary patterns and MM risk. Two studies have assessed this risk, albeit with a small number of MM cases. The EPIC-Oxford cohort and Oxford Vegetarian study (65 MM cases) showed that fish eaters, vegetarians and vegans had significantly reduced MM risk compared to meat eaters. The Nurses' Health Study and Health Professionals Follow-up Study (478 MM cases) showed a significantly increased MM risk in men with Empirical Dietary Inflammatory Pattern. Methods: The NIH-AARP Diet and Health study is a prospective cohort of 567,169 persons who completed a food frequency questionnaire in 1995-1996 and were followed until December 2011. Healthy Eating Index-2015 (HEI-2015), Healthy Diet Score (HDS), alternate Mediterranean Diet (aMED) and healthful Plant-based Diet Index (hPDI) scores were calculated using a priori defined methods and grouped into quartiles, with higher scores reflecting healthier eating patterns. We prospectively evaluated the association between pre-diagnosis dietary patterns and MM incidence in this cohort. Hazard ratios (HR) and 95% confidence intervals (95%CI) were estimated using multivariate Cox proportional hazards models adjusted for age at study entry, sex, race, body mass index, education, and total energy intake (by residual method). Sensitivity analysis was conducted to assess reverse causality by excluding MM cases diagnosed within one year of follow-up. Results: Among 392,589 participants (after exclusions), a total of 1,366 MM cases (59% males; 92% non-Hispanic whites) were identified during the follow-up period. Analysis revealed a significant association between hPDI scores and reduced MM risk (highest vs lowest quartile, HR 0.85; 95%CI 0.73-1.0; p=0.043) (Table). In sensitivity analysis (1,302 MM cases), the association was no longer significant (HR 0.87; 95%CI 0.74-1.03; p 0.09) but trended in the same direction. This may be due to small sample size, given MM is a rare disease. HEI-2015, HDS and aMED scores were not associated with MM risk. Conclusions: A healthful plant-based diet was associated with reduced MM risk in the NIH-AARP cohort. These results will help oncologists and patients make informed choices about their diet. To our knowledge, this is the largest epidemiologic study to date assessing pre-diagnosis dietary patterns and MM risk.

Amyloidosis: a case series and review of the literature.

BACKGROUND: Systemic amyloidosis is group of disorders characterized by the accumulation of insoluble proteins in tissues. The most common form of systemic amyloidosis is light chain amyloidosis, which results from the accumulation of misfolded immunoglobulins. The disease is progressive, with treatment targeted at the underlying plasma cell dyscrasia. Since essentially any organ system can be affected, the presentation is variable and delays in diagnosis are common. Given this diagnostic difficulty, we discuss four different manifestations of light chain amyloidosis. CASE PRESENTATIONS: In this case series, we discuss four cases of light chain amyloidosis. These include cardiac, hepatic, and gastrointestinal as well as autonomic and peripheral nerve involvement with amyloidosis. The patients in our series are of Caucasian background and include a  69-year-old female, a 29-year-old female, a 68-year-old male, and a 70-year-old male, respectively. The case discussions highlight variability in presentation and diagnostic challenges. CONCLUSIONS: Amyloidosis is a rare but serious disease that is often complicated by long delays in diagnosis. Morbidity and mortality can sometimes be limited if diagnosed earlier. We hope our real life cases will contribute to understanding and to early suspicion that can lead to early diagnosis and management.

Dietary and microbiome evidence in multiple myeloma and other plasma cell disorders.

Multiple Myeloma (MM) remains an incurable plasma cell neoplasm. Although little is known about the etiology of MM, several metabolic risk factors such as obesity, diabetes mellitus, diet, and the human intestinal microbiome have been linked to the pathogenesis of MM. In this article, we provide a detailed review of dietary and microbiome factors involved in the pathogenesis of MM and their impact on outcomes. Concurrent with treatment advancements that have improved survival in MM, focused efforts are needed to reduce the burden of MM as well as improve MM specific and overall outcomes once MM is diagnosed. The findings presented in this review will provide a comprehensive guide on the evidence available to date of the impact of dietary and other lifestyle interventions on the gut microbiome and on MM incidence, outcomes, and quality of life. Data generated from such studies can help formulate evidence-based guidelines for healthcare providers to counsel individuals at risk such as those with Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM) as well as MM survivors with respect to their dietary habits.

Spectrum of second primary malignancies and cause-specific mortality in pediatric and adult langerhans cell histiocytosis.

With the advent of targeted therapeutics in Langerhans cell histiocytosis (LCH), there is a growing survivor population that might be at risk for late mortality from non-LCH causes, including second primary malignancies (SPMs). We undertook a large study using the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the patterns of SPMs and cause-specific mortality among individuals with LCH (2000-2016) from the US. We found an increased risk of SPMs in the cohort (standardized incidence ratio [SIR] 2.07). The pediatric group was at a high risk of developing Hodgkin lymphoma (SIR 60.93) and non-Hodgkin lymphoma (SIR 60.88). People with adult-onset LCH were found to have a high risk of developing miscellaneous malignant cancers (SIR 11.43), which primarily included myelodysplastic syndrome. Adults were also at a high risk of developing carcinoma in-situ of vulva at 2-11 months [SIR 62.72] and B-ALL at 60-119 months [SIR 66.29] after LCH diagnosis. Additionally, 5% and 1% of the patients developed prior or concomitant malignancies with LCH, respectively. The 5 yr overall survival (OS) was 96.6% for pediatric and 88.5% for adult LCH cohorts. Most common cause of death was infections in pediatric and SPMs in adult LCH. Our study highlights that despite advances in treatments, people with LCH have an increased mortality risk from non-LCH causes when compared with the general population, including a high risk of SPMs.

Feasibility of Outpatient Stem Cell Transplantation in Multiple Myeloma and Risk Factors Predictive of Hospital Admission.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains the standard of care for multiple myeloma (MM) patients. Although outpatient ASCT has been shown to be safe and feasible, the procedure is overall rare with most patients in the US undergoing inpatient ASCT. Furthermore, hospitalization rates for patients that undergo outpatient ASCT remain high. Adequate markers that predict hospitalization during outpatient ASCT are lacking, yet would be of great clinical value to select patients that are suited to outpatient ASCT. In this study we aimed to elucidate differences between planned outpatient and inpatient ASCT and further evaluated clinical characteristics that are significantly associated with hospitalization during planned outpatient hospitalization. Factors that were significantly associated with a planned inpatient ASCT included an advanced MM disease stage, worse performance status as well as non-Caucasian race, while low albumin levels and female gender were significantly associated with hospitalization during outpatient ASCT. The results of this analysis provide crucial knowledge of factors that are associated with planned inpatient ASCT and hospitalization during outpatient ASCT and could guide the treating physician in decision-making and further facilitate outpatient transplantation.

A comprehensive review of the impact of obesity on plasma cell disorders.

Multiple myeloma (MM) remains an incurable plasma cell malignancy. Although little is known about the etiology of MM, several metabolic risk factors such as obesity, diabetes, poor nutrition, many of which are modifiable, have been linked to the pathogenesis of numerous neoplasms including MM. In this article, we provide a detailed summary of what is known about the impact of obesity on the pathogenesis of MM, its influence on outcomes in MM patients, and discuss potential mechanisms through which obesity is postulated to influence MM risk and prognosis. Along with advancements in treatment modalities to improve survival in MM patients, focused efforts are needed to prevent or intercept MM at its earliest stages. The consolidated findings presented in this review highlight the need for clinical trials to assess if lifestyle modifications can reduce the incidence and improve outcomes of MM in high-risk populations. Data generated from such studies can help formulate evidence-based lifestyle recommendations for the prevention and control of MM.

Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma.

Multiple myeloma (MM) patients frequently attain a bone marrow (BM) minimal residual disease (MRD) negativity status in response to treatment. We identified 568 patients who achieved BM MRD negativity following autologous stem cell transplantation (ASCT) and maintenance combination therapy with an immunomodulatory agent and a proteasome inhibitor. BM MRD was evaluated by next-generation flow cytometry (sensitivity of 10-5 cells) at 3- to 6-month intervals. With a median follow-up of 9.9 years from diagnosis (range, 0.4-30.9), 61% of patients maintained MRD negativity, whereas 39% experienced MRD conversion at a median of 6.3 years (range, 1.4-25). The highest risk of MRD conversion occurred within the first 5 years after treatment and was observed more often in patients with abnormal metaphase cytogenetic abnormalities (95% vs 84%; P = .001). MRD conversion was associated with a high risk of relapse and preceded it by a median of 1.0 years (range, 0-4.9). However, 27% of MRD conversion-positive patients had not yet experienced a clinical relapse, with a median follow-up of 9.3 years (range, 2.2-21.2). Landmark analyses using time from ASCT revealed patients with MRD conversion during the first 3 years had an inferior overall and progression-free survival compared with patients with sustained MRD negativity. MRD conversion correctly predicted relapse in 70%, demonstrating the utility of serial BM MRD assessment to complement standard laboratory and imaging to make informed salvage therapy decisions.

Predicting risk of progression in relapsed multiple myeloma using traditional risk models, focal lesion assessment with PET-CT and minimal residual disease status.

Not available.

Salvage Autologous Stem Cell Transplantation in Daratumumab-Refractory Multiple Myeloma.

Daratumumab, a CD38-targeting monoclonal antibody, has significantly improved survival rates in multiple myeloma (MM), yet patients who progress on Daratumumab have dismal clinical outcomes with an overall median of less than 10 months. While emerging novel modalities have shown promising results, the current study explores the use of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in heavily pretreated Daratumumab-refractory MM patients. We retrospectively investigated the outcome of 69 consecutive patients who received upfront ASCT. The median progression-free survival (PFS) for the entire patient cohort was 7.2 months with a median overall survival (OS) of 19.3 months. For patients with ≥very good partial response (VGPR), median PFS and OS improved to 9 months and 34 months, respectively. Achievement of MRD negativity in ≥VGPR did not further improve the outcome. A better performance status, younger age, longer time interval from initial MM diagnosis/initial ASCT to salvage ASCT and low-risk GEP70 were all associated with improved PFS and OS after salvage ASCT. Our results suggest a role for salvage ASCT in selected heavily pretreated and Daratumumab-refractory patients.

Coronary Artery Calcium Scoring in Young Adults: Evidence and Challenges.

PURPOSE OF REVIEW: This review aims to summarize the evidence and challenges of coronary artery calcium (CAC) scoring as a screening tool for coronary artery disease (CAD) in young adults. RECENT FINDINGS: Several cohort studies have highlighted the value of CAC scoring in CAD risk assessment in young adults. The largest study to date is the Coronary Artery Risk Development in Young Adults (CARDIA) study. The study examined patients at 18-30 years of age and demonstrated that the presence of any degree of CAC was associated with a higher risk of coronary events compared to zero CAC, with an incremental increase in the risk of events with higher scores. However, it is important to note that 70% of patients screened had CAC = 0 at the age of 56. Despite the evidence that higher CAC score cutoff used in guidelines for predicting cardiovascular risk may be "falsely reassuring," however, mass screening of young adults using CAC score may be challenging. The development of prediction tools and scoring systems to identify patients at higher risk of developing CAC based on known CAD risk factors may help reduce the number needed to screen to detect patients with positive CAC.