Outcomes of Patients with Myeloid Malignancies and Cardiovascular Disease Undergoing Allogeneic Stem Cell Transplantation.

INTRODUCTION/BACKGROUND: Reduced-intensity conditioning (RIC) and nonmyeloablative (NMA) regimens have enabled patients with cardiovascular disease (CVD) to undergo allogeneic stem cell transplantation (allo-HSCT). However, little is known about long-term outcomes, including cardiovascular (CV) complications. METHODS: We retrospectively studied 99 consecutive patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who underwent allo-HSCT between September 1, 2013, and November 30, 2020. Overall survival (OS), progression-free survival (PFS), nonrelapse mortality (NRM), cumulative incidence of relapse, and cumulative incidence of acute and chronic graft-versus-host disease (GvHD) were compared in patients with and without CV risk factors or disease. RESULTS: Preexisting CVD was present in 34 of 99 patients (34%). CVD patients more commonly had reduced-intensity conditioning (91% vs. 60%, p = 0.001) and unrelated donors (56% vs. 35%, p = 0.04). Early adverse cardiac events occurred more frequently in the CVD versus no-CVD group (38% vs. 14%), particularly arrhythmias (21% vs. 5%; p = 0.04). CVD patients tended to have poorer OS and PFS outcomes (HR = 1.98, [1.00, 3.92]; HR = 1.89, [0.96-3.72], respectively). OS rate at 1, 2, and 3 years for CVD versus no-CVD patients was 66% versus 72%, 55% versus 64%, and 46% versus 62%, respectively. Causes of death in the CVD and no-CVD groups were infections (53% vs. 28%), relapsed disease (32% vs. 52%), and CV events (10% vs. 3%). CONCLUSION: Based on these data, predictive models to identify patients with CVD with higher risk of post-allo-HSCT complications and mortality and strategies to mitigate these risks should be developed.

Long-Term Follow up of Blinatumomab in Older Patients with B-Cell Acute Lymphoblastic Leukemia.

Older adults who are diagnosed with acute lymphoblastic leukemia (ALL) and are treated with chemotherapy generally have poor outcomes. Blinatumomab is a CD19/CD3 bispecific T-cell engager that has been approved for the treatment of B-cell ALL in the relapsed/refractory setting or in patients with minimal residual disease (MRD) positivity. We previously reported on a small cohort of older adults with newly diagnosed Philadelphia chromosome negative B-cell ALL who were treated with blinatumomab monotherapy in the first line setting. This is a long-term follow up of those patients and their clinical courses. All five patients achieved complete remission (CR) after one cycle of blinatumomab, and three were MRD-negative. Two patients completed three cycles of blinatumomab, two patients completed four cycles of blinatumomab, and one patient completed 17 cycles of blinatumomab total. In the last four years, four of these patients had relapsed disease requiring additional therapy. Two patients are alive after 61 months and 57 months since their first cycle of blinatumomab. Two of the patients died at 10 months and one died at 20 months. Here we describe the long-term clinical courses of these patients.

Clinical outcomes of patients with acute myeloid leukemia and cardiovascular disease.

Incidence of both acute myeloid leukemia (AML) and cardiovascular disease (CVD) increases with age. We evaluated whether pre-existing CVD impacts clinical outcomes in AML. We retrospectively evaluated 291 consecutive adult AML patients treated at our institution, 2014-2020. Pretreatment comorbidities were identified by chart review. Outcomes included complete remission (CR) and CR with incomplete count recovery (CRi) rates, disease-free survival (DFS), overall survival (OS) and incidence of cardiovascular adverse events. CVD was present in 34% of patients at AML diagnosis. CVD patients had worse performance status (p=0.03) and more commonly had secondary AML (p=0.03) and received hypomethylating (HMA) agent-based therapy (72% vs 38%, p< 0.001). CVD (0.45 vs 0.71, p<0.001) and diabetes mellitus (HR= 0.24, 95% CI: 0.08 - 0.8, p= 0.01) were associated with lower probability of achieving CR/CRi. Accounting for age, performance status (PS), complex karyotype, secondary disease and treatment, CVD patients had shorter OS (HR=1.5, 95% CI: 1.1-2.2, p=0.002), with 1- and 3-year OS 44% vs 67% and 25% vs 40%, respectively, but there was no difference in cumulative incidence of relapse between patients with vs without CVD. Thus, CVD is an independent risk factor for lower response rate and shorter survival in AML patients.

Exploring the effects of racial and socioeconomic factors on timeliness of lung cancer diagnosis and treatment in Baltimore Veterans.

OBJECTIVES: To characterize the effect of racial and socioeconomic factors on the timeliness of lung cancer diagnosis and treatment in a single-center Veterans Affair Medical Center (VAMC) pulmonary nodule clinic. METHODS: We conducted a single-center retrospective review of all patients seen at the Baltimore VAMC pulmonary nodule clinic between 2013 and 2019 to identify key demographic factors, measures of neighborhood socioeconomic disadvantage, cancer staging and histopathologic information, and time elapsed between diagnosis and treatment. We excluded patients with pulmonary nodules undergoing active surveillance, prior history of lung cancer, metastases of a different primary origin, insufficient followup, or who had received care outside the VHA system. RESULTS: Median times to diagnosis and treatment of lung cancer were 28 and 73 days. There were no statistically significant differences in overall timeliness of diagnosis and treatment when stratified by race or measures of neighborhood socioeconomic disadvantage. CONCLUSIONS: The authors found no differences in timeliness of lung cancer care by race and socioeconomic status within the system. Despite general adherence to national standards in timeliness of care, there continues to be a need for improvements in the operational workflows to reduce time to diagnosis and treatment for all Veterans.

Prediction and control of number of cells in microdroplets by stochastic modeling.

Manipulation and encapsulation of cells in microdroplets has found many applications in various fields such as clinical diagnostics, pharmaceutical research, and regenerative medicine. The control over the number of cells in individual droplets is important especially for microfluidic and bioprinting applications. There is a growing need for modeling approaches that enable control over a number of cells within individual droplets. In this study, we developed statistical models based on negative binomial regression to determine the dependence of number of cells per droplet on three main factors: cell concentration in the ejection fluid, droplet size, and cell size. These models were based on experimental data obtained by using a microdroplet generator, where the presented statistical models estimated the number of cells encapsulated in droplets. We also propose a stochastic model for the total volume of cells per droplet. The statistical and stochastic models introduced in this study are adaptable to various cell types and cell encapsulation technologies such as microfluidic and acoustic methods that require reliable control over number of cells per droplet provided that settings and interaction of the variables is similar.

Effect of electrolyte and adsorbates on charging rates in mesoporous gold electrodes.

The classical model for porous electrodes reported by De Levie several decades ago (and expanded upon since then) was developed mainly to describe pores with micrometer-scale diameters. Presumably it will break down as pore diameters approach atomic dimensions. Mesoporous gold formed by dealloying is a valuable test platform for this because its 10 nm pores are on the boundary of this expected breakdown and because the electrochemical and surface properties of gold are relatively well understood. The De Levie model works for these electrodes at high salt concentrations, but under dilute conditions, there is not enough salt locally to charge the interface, increasing real impedance on intermediate time scales. Specific adsorption on pore walls can cause a similar increase and also cause an effective mobility decrease, tunable through electrolyte choice and the use of alkanethiol monolayers. These effects are not expected in micrometer-scale pores and are important considerations when designing devices with nanoporous electrodes.

Supercapacitive transport of pharmacologic agents using nanoporous gold electrodes.

In this study, nanoporous gold supercapacitors were produced by electrochemical dealloying of gold-silver alloy. Scanning electron microscopy and energy dispersive X-ray spectroscopy confirmed completion of the dealloying process and generation of a porous gold material with approximately 10 nm diameter pores. Cyclic voltammetry and chronoamperometry of the nanoporous gold electrodes indicated that these materials exhibited supercapacitor behavior. The storage capacity of the electrodes measured by chronoamperometry was approximately 3 mC at 200 mV. Electrochemical storage and voltage-controlled delivery of two model pharmacologic agents, benzylammonium and salicylic acid, was demonstrated. These results suggest that capacitance-based storage and delivery of pharmacologic agents may serve as an alternative to conventional drug delivery methods.