A Case of µ Heavy and λ Light Chain Amyloidosis in a Patient With Bi-Clonal (IgM κ and λ) Gammopathy Treated With Daratumumab.

Our case report is of an elderly male with a history of IgM κ lymphoplasmacytic lymphoma (LPL) presenting with generalized neuropathy and weakness. Due to his LPL history and worsening renal function, he underwent a renal biopsy revealing the presence of µ heavy and λ light chains, revealing a diagnosis of amyloidosis with unbound heavy & light chains (AHL), a rare type of amyloidosis. His bone marrow biopsy demonstrated κ light chain restriction by flow cytometry and amyloid deposition. The patient's serum had elevated free κ and λ light chains with a free light chain (FLC) ratio of 3.17. Serum immunofixation was positive for IgM κ and λ light chain clones. He completed six cycles of cyclophosphamide, bortezomib, dexamethasone, and rituximab (CyBorD+R), normalizing the FLC ratio. Still, he continued to present with persistently elevated M protein, IgM κ, and λ light chains on immunofixation. Thereafter, daratumumab, a human monoclonal antibody directed against CD38 expressed on myeloma cells was initiated, which led to a negative immunofixation study after two cycles accompanied by a reduction in protein excretion in the urine. The patient achieved a complete hematological response with daratumumab. To date, our case is the only reported µ heavy and λ light chain amyloidosis patient with bi-clonal (IgM κ and λ) gammopathy to be successfully treated with daratumumab.

County-level variation in healthcare coverage and ischemic heart disease mortality.

BACKGROUND: Healthcare coverage has been shown to have implications in the prevalence of coronary artery disease. We explore the impact of lack of healthcare coverage on ischemic heart disease (IHD) mortality in the US. METHODS: We obtained county-level IHD mortality and healthcare coverage data from the CDC databases for a total of 3,119 US counties. The age-adjusted prevalence of current lack of health insurance among individuals aged 18 to 64 years were obtained for the years 2018 and 2019 and were placed into four quartiles. First (Q1) and fourth quartile (Q4) had the least and highest age-adjusted prevalence of adults without health insurance, respectively. IHD mortality rates, adjusted for age through the direct method, were obtained for the same years and compared among quartiles. Ordinary least squares (OLS) regression for each demographic variable was conducted with the quartiles as an ordinal predictor variable and the age-adjusted mortality rate as the outcome variable. RESULTS: We identified a total of 172,942 deaths related to ischemic heart disease between 2018 and 2019. Overall AAMR was higher in Q4 (92.79 [95% CI, 92.35-93.23]) compared to Q1 (83.14 [95% CI, 82.74-83.54]), accounting for 9.65 excess deaths per 100,000 person-years (slope = 3.47, p = 0.09). Mortality rates in Q4 for males (126.20 [95% CI, 125.42-126.98] and females (65.57 [95% CI, 65.08-66.05]) were higher compared to Q1 (115.72 [95% CI, 114.99-116.44] and 57.48 [95% CI, 57.04-57.91], respectively), accounting for 10.48 and 8.09 excess deaths per 100,000 person-years for males and females, respectively. Similar trends were seen among Hispanic and non-Hispanic populations. Northeastern, Southern, and Western regions had higher AAMR within Q4 compared to Q1, with higher prevalence of current lack of health insurance accounting for 49.2, 8.15, and 29.04 excess deaths per 100,000 person-years, respectively. CONCLUSION: A higher prevalence of adults without healthcare coverage may be associated with increased IHD mortality rates. Our results serve as a hypothesis-generating platform for future research in this area.

Myelodysplastic Syndrome After Anti-CD19 Chimeric Antigen Receptor T-cell Therapy: A Case Series.

The utility of CD19-targeted chimeric antigen receptor T-cell (CAR-T cell) therapy in the management of refractory/relapsed B-cell malignancies has increased tremendously in recent times. In addition to cytokine release syndrome (CRS), neurotoxicity, and infections, CAR-T cell patients develop cytopenias, with about 15% of the patients continuing to have severe cytopenias up to three months after treatment. Retrospective reviews have reported the development of myelodysplastic syndrome (MDS) in patients undergoing CAR-T cell therapy. Here, we describe four cases of MDS and/or clonal cytopenias of undetermined significance (CCUS), developing after CAR-T cell therapy. A retrospective review of four patients with relapsed/refractory B-cell lymphomas treated with CD19-directed autologous CAR-T cell was conducted at our institution. The median age was 72.5 years (range 63-76). Three of the four patients had double-hit diffuse large B-cell lymphoma (DLBCL). The median number of lines of therapy before CAR-T cell was three. Only one patient had a prior autologous stem cell transplant (ASCT). The median time to diagnosis of MDS/CCUS from CAR-T cell therapy was three months. Two cases of CCUS diagnosed were at one- and two-month post-CAR-T cell, and two cases of MDS were diagnosed at 10 and 26 months. None of the patients had dysplastic clones before the initiation of CAR-T cell therapy. Only one patient was found to have CCUS-developed CRS post-CAR-T cell requiring treatment with tocilizumab and steroids. Three patients showed complete response, with one showing a very good partial response. All the patients were in remission with no additional therapies post-CAR-T cell. One patient died secondary to COVID-19-related complications. Four patients with prolonged cytopenias were found to have either MDS or CCUS after CAR-T cell therapy. Two CCUS cases underwent bone marrow evaluation early in the course of cytopenias and may develop into MDS, acute myeloid leukemia (AML), or myeloproliferative neoplasm over time. Our retrospective case series review, compared to previous studies, constitutes of patients with no prior clonal hematopoiesis-related cytogenetic abnormalities, fewer lines of therapy, and only one patient with previous hematopoietic stem cell transplantation (HSCT). Based on the upcoming data and our review, a bone marrow biopsy with next-generation sequencing (NGS) is imperative in patients with prolonged cytopenias after CAR-T cell therapy. A diagnosis of CCUS/MDS in these cases can help guide treatment.

Utility of the social vulnerability index to risk stratify atrial fibrillation mortality outcomes.

Background: Multiple methods of quantifying social determinants of health exist, such as the social vulnerability index (SVI). We assess the impact of the SVI on atrial fibrillation (AF)-related cardiovascular disease mortality. Methods: CDC databases were used to obtain mortality and SVI information. Age-adjusted mortality rates (AAMR) were compared among all US counties, aggregated by SVI quartiles. Results: AAMR was not increased in counties within the highest SVI quartile, consistent across gender and geographic subgroups. Conclusions: Increased SVI is a poor marker to predict mortality outcomes associated with AF.

The enigma of persistent hypertriglyceridemia: A case report.

A patient with a history of Mandibular hypoplasia, Deafness, Progeroid Features Associated Lipodystrophy Syndrome (MDPL), familial lipodystrophy presented with hypertriglyceridemia induced pancreatitis with triglycerides in the 3000s. This lipodystrophy occurs due to a mutation in the POLD1 gene (DNA polymerase delta 1). MDPL, hypertriglyceridemia, pancreatitis, POLD1.