Citations

Abstract Background: Hematologic toxicity, including early and prolonged neutropenia, anemia, and thrombocytopenia, is among the most common and clinically significant complications after CD19, CD20, CD22 and BCMA-directed CAR-T therapy. Several clinical scoresmost notably CAR-HEMATOTOX (CAR-HT) and the refined ALL-HThave been developed to predict post-infusion cytopenias, but their comparative performance across diseases has not been systematically evaluated. No prior review has summarized existing models or assessed the need for AI-based predictive approaches. Methods: We conducted a systematic review of studies that developed or validated predictive models or risk scores for hematologic toxicity after CAR-T therapy in hematologic malignancies. Eligible studies included clinical, cytokine-based, or composite predictors and reported discrimination metrics such as area under the curve (AUC). Extracted variables included CAR-T product, target antigen, disease type, predictors used, model type, validation strategy, and performance statistics. Results were synthesized qualitatively due to heterogeneity in model structure and outcome definitions. Results: Studies on the CAR-HT score in B-cell lymphomas and multiple myelomas reported AUC values of 0.89 and 0.82, respectively, for predicting severe or long-term neutropenia after CD19 and BCMA-directed CAR-T therapy. Studies on the ALL-HT score (a modified/refined version of CAR-HT replacing ferritin with bone-marrow burden to improve discrimination in B-ALL) reported AUC 0.84-0.90 for predicting prolonged neutropenia and worse overall survivability (OS) after CD19/CD22 CAR-T. A multicenter study including aggressive/indolent NHL, MM/PCL, and ALL patients treated with CD19, CD20, or BCMA CAR-T reported AUC 0.87 (eIPM-Pre) and 0.88 (eIPM-Post) for predicting ICA-HT. A CD19 CAR-T study in B-ALL and LBCL reported AUC 0.85 for an early hematotoxicity nomogram using TNF- and CRP. Conclusion: Existing prediction tools for hematologic toxicity after CAR-T therapy demonstrate strong but disease-specific performance. Yet inconsistent endpoints and heterogeneous predictors limit clinical generalizability. No current model incorporates contemporary AI or machine-learning methods, underscoring a significant unmet need. Advanced predictive frameworks may allow earlier identification of patients at risk for severe or prolonged cytopenias and guide more individualized supportive care, with the potential to reduce downstream complications. Citation Format: Mansha Gupta, Abhijith Vemulapalli, Swathi Cherukuri, Rithish Nimmagadda, Akhil Jain. Predictive models for hematologic toxicity after CAR-T therapy: A systematic review of current risk scores and unmet AI needs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5202.

7018 Background: CAR-T cell therapy represents a notable advancement in treating relapsed/refractory (R/R) hematological malignancies. Adverse events include CRS, infections, and neurological and cardiac complications. While there are reports from major academic institutions on the adverse effects of CAR-T therapy, we used data from the National Inpatient Sample (NIS) to gather national estimates of complications related to CAR-T therapy. Methods: A retrospective study was conducted to analyze patients who underwent CAR-T cell therapy by utilizing appropriate ICD-10-PCS procedure codes (XW033C3, XW043C3, XW23346, XW24346, XW23376, and XW24376) from NIS 2019 to 2021. Data regarding infections, toxic encephalopathy (a surrogate for neurological toxicity), and adverse cardiac events were extracted using relevant ICD-10-CM diagnostic codes. Patients experiencing various grades of CRS were identified through specific ICD-10 codes available in 2021 (Grades 1-5: D89.831-D89.835). Results: This study analyzed 6515 patients who underwent CAR-T cell therapy from January 2019 to December 2021. Among them, 60.7% were male. 74.6% were Caucasian, 11.7% were Asian and 6.7% were African American. 49.8% of patients had private insurance, 36.2% had Medicare, and 8.6% had Medicaid. 6.8% of patients were diagnosed with pneumonia, while sepsis occurred in 7.4% of patients and 3% experienced septic shock. 19.4% of patients experienced cardiac arrhythmias, and major cardiovascular events were recorded in 4.7% of the cohort. Acute myocardial infarction and stroke were documented in 0.6 and 1.2% of patients, respectively. Toxic encephalopathy was reported in 19.7% of patients. Among 2235 patients identified to have received CAR-T in 2021, 59.7% developed CRS. Grade 1 and grade 2 CRS were reported in 32% and 21% of patients, respectively, while grade 3 and grade 4 reactions were noted in 4.7% and 2% of patients, with no cases of grade 5 identified. The mean total cost of hospitalization was 308,364$, and the mean length of hospital stay was 19.5 days. The overall in-hospital mortality rate was 3.4%. Conclusions: Our study describes real-world outcomes from a large dataset of CAR-T patients. Infections pose a significant challenge with CAR-T therapy, highlighting the importance of early detection and timely antimicrobial treatment. CRS is common, with a 60% incidence, similar to previous clinical trials (55%). Immediate management is crucial for addressing CRS toxicity. Adverse neurological and cardiovascular incidents are often reported, emphasizing the need for meticulous monitoring and coordinating multidisciplinary care plans. The financial burdens also bear mentioning: CAR-T therapy costs significantly higher than autologous stem cell transplants. Further studies to address these issues are warranted.

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

Cerebral embolic protection devices (CEPD) during transcatheter aortic valve replacement (TAVR) have been shown to lower the risk of stroke during the procedure. However, their long-term and clinical effects on neuro-cognition are unknown. Therefore, we hypothesized the benefit of CEPD in TAVR patients with a prior history of stroke or transient ischemic attack (TIA). National Inpatient Sample (2019) and International Classification of Diseases, 10th Revision codes were used to identify patients undergoing TAVR with prior stroke or TIA. Propensity-matched analysis was performed to adjust for baseline characteristics and comorbidities. Primary outcome measures were postoperative stroke and all-cause mortality. Length of stay and hospital cost were secondary outcomes. Of 8450 unmatched TAVR patients with prior stroke or TIA in 2019, 1095 (13%) utilized CEPD. After propensity matching previous myocardial infarction (MI), coronary artery bypass grafting, and drug abuse were higher in the TAVR-only cohort. Postoperative stroke rate (1.4% vs 2.2%; P = 0.081) and odds [adjusted odds ratio (aOR), 0.48; 95% confidence interval (CI), 0.11–2.17; P = 0.341] were lower in the CEPD group. There was no difference in all-cause in-hospital mortality between the 2 groups (0.9% vs 1.0%). Length of stay (3 vs 2 days, P <0.001) and hospital expenditure ($172,711 vs $162,284; P = 0.002) were higher for the TAVR-only cohort. CEPD in TAVR patients with prior stroke or TIA did not show statistically significant postoperative stroke benefits. However, further larger-scale prospective studies are needed to evaluate the long-term neurocognitive benefits of CEPD in these patients. As the use of TAVR continues to expand, optimizing peri-procedural strategies such as the use of CEPD remains a critical area of research to improve patient outcomes.

Prediabetes is a risk factor for ischemic stroke in atrial fibrillation (AF) patients, yet, its impact on recurrent stroke in AF patients remains understudied. Using the 2018 National Inpatient Sample, we investigated the link between Prediabetes and recurrent stroke in AF patients with prior stroke or transient ischemic attack (TIA). Among 18,905 non-diabetic AF patients, 480 (2.5%) had prediabetes. The prediabetic group, with a median age of 78, exhibited a two-fold higher risk of recurrent stroke compared to the non-prediabetic cohort (median age 82), as evidenced by both unadjusted (OR 2.14, 95% CI 1.72–2.66) and adjusted (adjusted for socio-demographics/comorbidities, OR 2.09, 95% CI 1.65–2.64, p < 0.001). The prediabetes cohort, comprising more male and Black patients, demonstrated associations with higher Medicaid enrollment, admissions from certain regions, and higher rates of hyperlipidemia, smoking, peripheral vascular disease, obesity, and chronic obstructive pulmonary disease (all p < 0.05). Despite higher rates of home health care and increased hospital costs in the prediabetes group, the adjusted odds of all-cause mortality were not statistically significant (OR 0.55, 95% CI 0.19–1.56, p = 0.260). The findings of this study suggest that clinicians should be vigilant in managing prediabetes in AF patients, and strategies to prevent recurrent stroke in this high-risk population should be considered.

Background: Impaired left ventricular (LV) global longitudinal strain (GLS) is associated with worse outcomes in patients with severe aortic stenosis (AS). However, its prognostic value in patients with moderate AS is still unknown. The aim of this study is to investigate the impact of LV GLS on outcomes of patients with moderate AS. Methods: PubMed/Medline, Scopus, and Google Scholar databases were systematically reviewed to find relevant studies through June 2023 reporting data on the relationship between the LV GLS and long-term mortality in patients with moderate AS. Binary random effects models were used to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). I2 statistics were used to interpret heterogeneity, with I2>75% indicating substantial inter-study variation. Leave-one-out meta-analysis was performed to evaluate the effect of each study on the overall estimate. A p<0.05 was considered statistically significant. Results: A total of 172 studies were reviewed, and 4 studies between 2000-2023 were included in our meta-analysis with a median follow-up of 48.5 months and GLS cut-off varying from 11% to 16%. The pooled univariate analysis revealed a significant association between LV GLS and long-term mortality in patients with moderate AS with a pooled OR of 2.02 (95CI 1.04-3.93) p=0.04, I2=94.25%. The multivariate analysis, after adjusting for overall modifiable risk factors, yielded significant results, with an adjusted odds ratio (aOR) of 1.56 (95CI 1.21-2.01) p<0.01, I2=89.48%. Sensitivity analysis, using leave-one-out method, demonstrated robustness and stability of the results with aOR 1.56 (95CI 1.21-2.01) p<0.01. Conclusions: In patients with moderate AS, impaired LV GLS is associated with an increased risk for all-cause mortality. If further randomized studies confirm the prognostic ability of impaired GLS, moderate AS can be redefined, and GLS can be considered in determining the optimal timing for aortic valve intervention.

Background: Catheter ablation (CA) is an effective and potentially curative treatment in patients with atrial fibrillation (AF). However, the recurrence of AF following CA treatment in cases of persistent atrial fibrillation (PeAF) remains a significant concern. This study aims to establish a correlation between the peak flow velocity of the left atrial appendage (LAAV) and the AF recurrence post-CA for PeAF. Methods: PubMed/Medline, EMBASE, and SCOPUS databases were systematically reviewed to find studies through June 2023 reporting data on the relationship between the LAAV and the recurrence of AF in individuals who have undergone CA for PeAF. Binary random effects models were used to estimate pooled outcomes. I2 statistics were used to interpret heterogeneity, with I 2 >75% indicating substantial inter-study variation. Leave-one-out meta-analysis was performed to evaluate the effect of each study on the overall estimate. A p<0.05 was considered statistically significant. Results: A total of 9 studies between 2000-2023 were included in our meta-analysis. The pooled univariate analysis revealed no association between LAAV and recurrence of AF in individuals who have undergone CA with a pooled OR of 1.09 (95CI 0.96-1.22) p=0.45, I2=86.59%. The multivariate analysis, after adjusting for overall modifiable risk factors, yielded significant results, with an adjusted odds ratio (aOR) of 1.41 (95CI 1.15-1.74) p<0.01, I2=85.24%. Sensitivity analysis, using the leave-one-out method&nbsp;demonstrated the robustness and stability of the results, indicating that no single study disproportionately influenced the overall&nbsp;findings with aOR 1.41 (95CI 1.15-1.74) p<0.01. Conclusions: This meta-analysis revealed that low LAAV is associated with high-risk of AF recurrence following CA. Identifying a specific subgroup of individuals at high risk of AF recurrence with the help of pre-CA LAA velocity will facilitate the early institution of alternative treatment strategies.

Background: The use of cannabis in cancer patients has gained significant attention due to its analgesic properties, which help alleviate cancer-related pain. Studies have also shown the interference of cannabis with the coagulation system. We aimed to study the impact of cannabis use disorder (CUD) and Pulmonary embolism (PE) on outcomes in female breast cancer survivors, considering reports suggesting significant overlap between recreational and medicinal use. Our objective was to compare outcomes in CUD+ (with cannabis use disorder) and CUD- (without cannabis use disorder) cohorts to gain critical insights into this group and understand the impact of CUD on PE-related hospitalization and outcomes. Methods: National Inpatient Sample (NIS) data from 2020 was utilized in order to analyze inpatient cohorts of PE hospitalizations. The International Classification of Diseases 10 (ICD 10) codes for pulmonary embolism, cannabis use disorder, and female breast cancer were utilized to classify cohorts. All cases of female breast cancer and pulmonary embolism with an age &gt;18 years were included in the final analysis. The primary outcome was the impact of CUD on PE-related hospitalizations in female breast cancer survivors. We also compared demographic correlations and comorbidities affecting outcomes between cohorts. Results: This study included a total of 508065 admissions among breast cancer survivors, with a median age of 74 years for the entire cohort. The prevalence of PE admissions was lower in CUD+ cohort compared to CUD- cohort (1.3% vs. 2.1%). The CUD+ cohort was relatively younger (median 66 vs 74 years, p&lt;0.001). Overall, admission rates were higher among white patients (77%) and this trend was statistically significantly higher in the 76-100 th percentile household income group (p&lt;0.002) compared to CUD+(50%) and CUD-(26.5%). Most admissions were non-elective (95.4%), with no statistical significance between CUD- and CUD+ patients (p=0.16). The majority of readmissions occurred in urban teaching hospitals (75.5%), with no significant difference observed between CUD- and CUD+ patients (p=0.111). Regionally, the South had a higher admission rate (37.2%) compared to other regions and this difference was statistically significant (p&lt;0.001) between CUD- and CUD+ patients. Among the coexisting comorbidities, hypertension showed a significant difference between CUD- (70%) and CUD+(37.5%) patients (p&lt;0.001). Alcohol use disorder (p&lt;0.001) and cancer (p&lt;0.001) had significant associations with CUD+, along with prior myocardial infarction (p=0.005) and drug use (p&lt;0.001) were significantly associated with CUD+.Furthermore, there was difference in routine patient disposition between between CUD-(45.3%) and CUD+(37.5%),(p=0.033) and length of stay (4 VS 2 days), (p=0.033) and cost of stay (47033 vs 27668 $), (p=0.017). The multivariable logistic regression analysis showed that the odds of PE-related hospitalization in CUD+ vs CUD- cohorts among female breast cancer survivors were not statistically significant, with an OR of 0.79 (CI: 0.38-1.62, p=0.512). Subgroup analysis by age demonstrated no statistically significant differences in odds for PE-related hospitalization between CUD+ and CUD- cohorts. For the age group of 18-44 years, the OR was 1.37 (CI: 0.18-10.60, p=0.762). In the 45-64 years age group, the OR was 0.48 (CI: 0.15-1.53, p=0.215), and for those aged ≥65 years, the OR was 1.32 (CI: 0.48-3.67, p=0.590). Furthermore, the analysis by race indicated that the odds of PE-related hospitalization did not reach statistical significance in both white and black female breast cancer survivors with CUD. For white patients, the OR was 0.64 (CI: 0.23-1.73, p=0.375), while for black patients, the OR was 1.15 (CI: 0.38-3.46, p=0.804). Conclusion: Among female breast cancer survivors, the presence of CUD did not show a statistically significant impact on the odds of PE-related hospitalization. Subgroup analysis by age and race also revealed no significant differences in the odds of PE-related hospitalization between CUD+ and CUD- cohorts. These findings underscore the importance of considering CUD when managing pulmonary embolism in breast cancer survivor females and emphasize the need for further research to understand the complex interplay between these factors.

Abstract Background Inflammation plays a potential role in heart failure (HF) etiology and prognosis. Neutrophil-to-Lymphocyte ratio (NLR) is a simple, routinely available lab criteria. In this meta-analysis, we sought to investigate the role of NLR on HF outcomes which remains unexplored. Methods PubMed, Embase and Scopus were systematically screened to find studies through August 2022, reporting data on association of HF related outcomes [all-cause mortality (ACM), cardiovascular (CV) death, in-hospital, HF readmissions and composite events] and NLR. Random effects models and I2 statistics were used to estimate pooled odds of outcomes and heterogeneity. Leave one out sensitivity analysis was performed. Results A total of 11 studies (6 retrospective and 5 prospective, 4 studies from Asia and Europe each, 2 from the US and 1 multicenter study) including 12954 patients (mean age: 69 years, Males 57.2%) from 2011 to 2022 with an average follow up duration of 54.8 months were included. Elevated NLR was significantly associated with ACM (aOR 1.80, 95%CI 1.46-2.22, p&lt;0.01, Table 1), HF readmissions (aOR 2.53, 95% CI 1.60-3.99), in-hospital mortality (aOR 3.26, 95% CI 1.76- 6.02), CV mortality (aOR 1.84, 95%CI 1.03-3.31) and composite CV outcome including heart transplant (OR 2.07, 95% CI 1.32-3.25), p&lt;0.001. Conclusion Elevated NLR was significantly associated with worse outcomes in HF patients. The NLR test might potentially be useful in identifying high-risk HF patients and curtail worse outcomes.

Background: Obstructive sleep apnea (OSA) increases the risk of stroke and cardiovascular diseases. However, its impact on geriatric patients with a prior history of stroke/transient ischemic attack (TIA) has not been adequately studied. Methods: We utilized the 2019 National Inpatient Sample in the US to identify geriatric patients with OSA (G-OSA) who had a prior history of stroke/TIA. We then compared subsequent stroke (SS) rates among sex and race subgroups. We also compared the demographics and comorbidities of SS+ and SS− groups and utilized logistic regression models to assess outcomes. Results: Out of 133,545 G-OSA patients admitted with a prior history of stroke/TIA, 4.9% (6520) had SS. Males had a higher prevalence of SS, while Asian-Pacific Islanders and Native Americans had the highest prevalence of SS, followed by Whites, Blacks, and Hispanics. The SS+ group had higher all-cause in-hospital mortality rates, with Hispanics showing the highest rate compared to Whites and Blacks (10.6% vs. 4.9% vs. 4.4%, p < 0.001), respectively. Adjusted analysis for covariates showed that complicated and uncomplicated hypertension (aOR 2.17 [95% CI 1.78–2.64]; 3.18 [95% CI 2.58–3.92]), diabetes with chronic complications (aOR 1.28 [95% CI 1.08–1.51]), hyperlipidemia (aOR 1.24 [95% CI 1.08–1.43]), and thyroid disorders (aOR 1.69 [95% CI 1.14–2.49]) were independent predictors of SS. The SS+ group had fewer routine discharges and higher healthcare costs. Conclusions: Our study shows that about 5% of G-OSA patients with a prior history of stroke/TIA are at risk of hospitalization due to SS, which is associated with higher mortality and healthcare utilization. Complicated and uncomplicated hypertension, diabetes with chronic complications, hyperlipidemia, thyroid disorders, and admission to rural hospitals predict subsequent stroke.