Chronic lymphocytic leukemia (CLL) is a mature B cell neoplasm with a predilection for older individuals. While previous studies have identified epigenetic signatures associated with CLL, whether age-related DNA methylation changes modulate CLL relapse remains elusive. In this study, we examined the association between epigenetic age acceleration and time to CLL relapse in a publicly available dataset. DNA methylation profiling of 35 CLL patients prior to initiating chemoimmunotherapy was performed using the Infinium HumanMethylation450 BeadChip. Four epigenetic age acceleration metrics (intrinsic epigenetic age acceleration [IEAA], extrinsic epigenetic age acceleration [EEAA], PhenoAge acceleration [PhenoAA], and GrimAge acceleration [GrimAA]) were estimated from blood DNA methylation levels. Linear, quantile, and logistic regression and receiver operating characteristic curve analyses were conducted to assess the association between each epigenetic age metric and time to CLL relapse. EEAA (p = 0.011) and PhenoAA (p = 0.046) were negatively and GrimAA (p = 0.040) was positively associated with time to CLL relapse. Simultaneous assessment of EEAA and GrimAA in male patients distinguished patients who relapsed early from patients who relapsed later (p = 0.039). No associations were observed with IEAA. These findings suggest epigenetic age acceleration prior to chemoimmunotherapy initiation is associated with time to CLL relapse. Our results provide novel insight into the association between age-related DNA methylation changes and CLL relapse and may serve has biomarkers for treatment relapse, and potentially, treatment selection.
e19524 Background: CLL accounts for about one-quarter of the new cases of leukemia and affects mainly elderly population. Recent literature highlights increased cardiovascular events in patients with CLL, notably those being treated with targeted therapy such as Bruton tyrosine kinase inhibitors. Here we examine data obtained from the National Inpatient Sample to find out incidence, predictors and outcomes of cardiovascular events in patients with CLL. Methods: We analyzed the National inpatient database from year 2019 and extracted the data of all patients with CLL. Multivariate regression analysis was performed to determine the aforementioned outcomes in CLL patients. Results: CLL patients showed increased odds of all cause in-hospital mortality (Adjusted Odds ratio (AOR) 1.28, 95% CI 1.19-1.38, P<0.001) in comparison to general adult population. CLL patients had higher odds of developing Atrial fibrillation (AOR 1.11, 95% CI 1.06-1.15 P <0.001) compared to patients without CLL. CLL patients had significantly higher odds of cardiac tamponade and pericardial effusion (AOR 1.64, 95% CI 1.10-2.42, P<0.001, 1.65 95% CI 1.43-1.92, P<0.001) respectively. Odds of congestive heart failure (AOR 0.97, 95% CI 0.93-1.01, P0.10) and atrial flutter (AOR 1.03, 95% CI 0.93-1.17, P 0.55) were similar between CLL patients and general adult populations. Patients with CLL have Increased mean hospital length of stay (adjusted mean LOS 0.51, 95% CI 0.42-0.61, p<0.001) and mean total hospital charges (adjusted mean charges 2006$, 95% CI 173$-3840$, P 0.03). [Table] We investigated the predictors of inpatient mortality in CLL patients and found that increase in age, black race, acute kidney injury, alcohol use, malnutrition and weekend admissions were associated with higher odds of mortality, whereas smoking, obesity, and female gender showed lower odds of mortality. Conclusions: CLL patients are at increased risk of developing atrial fibrillation, pericardial effusion, pericardial tamponade and all-cause in hospital mortality compared to their non-CLL counterparts, even after accounting for variables such as age, gender etc. Moreover, CLL patients have higher inpatient mortality associated with certain factors such as age progression, AKI, black race, alcohol abuse and malnutrition. Patients should be referred to cardiologist early and cardiovascular status should be optimized especially before initiating targeted therapy.[Table: see text]
e18801 Background: Clostridioides difficile infection (CDI) is notorious for its perilous effect on frail patients, but its assault is even more so threatening on cancer patients as they are more prone to CDI due to damage to intestinal mucosa by chemotherapy agents and weak immune system, hence higher risk of getting affected from hospital-acquired infections. Here we analyze National inpatient sample database (NIS) of hospitalized patients with solid tumors to find out aftermath of CDI in this particular patient population. Methods: We used NIS database from year 2019 and recruited all patients admitted with C. diff colitis with underline solid tumors with or without metastatic disease. We used international classification of disease,10th revision (ICD-10) codes to identify these patients. Our outcomes of interest were all cause inpatient mortality, acute kidney injury (AKI), sepsis, ICU admission, pressor use and hospital resource utilization including mean length of stay (LOS) and mean total charges. Using STATA 17, we performed the multivariate regression analysis. Results: A total of 15,161 (1.41%) hospitalizations due to principal diagnosis of C. diff Colitis were recorded in solid tumor patients in year 2019. Patients with history of solid tumors who were admitted with C. diff colitis had higher adjusted odds of all-cause in-hospital mortality (AOR 1.23, 95% CI1.08-1.41, P 0.002) compared to patients without underline solid tumor. These patients also had higher odds of sepsis (AOR 2.22, 95% CI 1.89-2.59, P < 0.001), AKI (AOR 1.91, 95% CI 1.73-2.10, P < 0.001), ICU admission (AOR 1.66, 95% CI 1.39-1.97, P < 0.001) and pressors use (AOR 1.82, 95% CI 1.38-2.40, P < 0.001). Patients with underline solid tumors who developed C. diff colitis had increased mean LOS (AOR 3.88, 95% CI 3.41-4.34, P < 0.001). These patients also incurred more hospital charges (Co-efficient 33836$, 95% CI 25907$-41766$, p < 0.001). [Table]. Conclusions: Patients with solid tumors admitted with CDI have an increased risk of sepsis, AKI, ICU admission and in-hospital mortality. They also have a significantly longer duration of hospital stay; hence higher cost of care. There is a dire need for awareness regarding strict contact precautions, hand hygiene, effective environmental cleaning, minimizing antibiotics use/adherence to antibiotic stewardship programs, using prophylactic vancomycin where indicated, avoidance of unnecessary hospital visits utilizing telehealth, etc. and aggressive management of CDI in patients admitted to hospital with solid tumors.[Table: see text]
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