Therapy In Recipients Research Articles

Cytomegalovirus Infections in Hematopoietic Stem Cell Transplant: Moving Beyond Molecular Diagnostics to Immunodiagnostics

Human CMV, regularly reactivated by simple triggers, results in asymptomatic viral shedding, powerful cellular immune responses, and memory inflation. Immunocompetent individuals benefit from a robust immune response, which aids in viral management without causing clinically significant illness; however, immunodeficient individuals are always at a higher risk of CMV reactivation and disease. Hematopoietic stem cell transplant (HSCT) recipients are consistently at higher risk of CMV reactivation and clinically significant CMV illness due to primary disease, immunosuppression, and graft vs. host disease. Early recovery of CMV-CMI responses may mitigate effects of viral reactivation in HSCT recipients. Immune reconstitution following transplantation occurs spontaneously and is mediated initially by donor-derived T cells, followed by clonal growth of T cells produced from graft progenitors. CMV-specific immune reconstitution post-transplant is related to spontaneous clearance of CMV reactivation and may eliminate the need for prophylactic or pre-emptive medication, making it a potential predictive marker for monitoring CMV reactivation. This review highlights current thoughts and therapeutic options for CMV reactivation in HSCT, with focus on CMV immune reconstitution and post-HSCT monitoring. Immune monitoring aids in risk stratification of transplant recipients who may progress from CMV reactivation to clinically significant CMV infection. Implementing this approach in clinical practice reduces the need for periodic viral surveillance and antiviral therapy in recipients who have a high CMV-CMI and thus may experience self-limited reactivation. Therefore, in the age of precision medicine, it is critical to incorporate CMV-specific cellular immune surveillance into conventional procedures and algorithms for the management of transplant recipients.

Timeline and outcomes of viral and fungal infections after Chimeric Antigen Receptor (CAR) T-cell therapy: A large database analysis

ObjectivesThis large database analysis aims to describe the incidence, timeline, and risk factors for viral and fungal infections after chimeric antigen receptor (CAR) T-cell therapy. MethodsWe queried a global research network database, TriNetX, for patients who received CAR T-cell therapy, who were identified and followed for the development of viral and fungal infections. Baseline demographic, oncologic history, laboratory data and medication histories were collected. We evaluated risk factors for respiratory viral infections (RVI), herpesvirus, fungal infections and mortality using Cox regression. ResultsA total of 2,256 patients who received CAR T-cell therapy were included, 1,867 (82.7%) were CD19-targeted and 400 (17.7%) were BCMA-targeted. Following CAR T-cell infusion, RVI were the most prevalent (23.3%) with a median onset of 160 days (IQR 52-348 days), while herpesvirus and fungal infections were less frequent, occurring in 13.6% and 11.4% of cases with median onsets of 71 (IQR 18-252) and 73 days (IQR 14-236 days), respectively. On multivariable Cox regression, independent predictors of RVI included acute lymphoblastic leukemia (ALL, HR 1.61), prior hematopoietic cell transplant (HCT, HR 1.29), cytokine release syndrome (CRS, HR 1.41), hemophagocytic lymphohistiocytosis (HLH, HR 1.96), and glucocorticoids (HR 3.37). Prior HCT (HR 2.00), hypogammaglobulinemia (HR 1.51), immune-effector cell-associated neurotoxicity syndrome (ICANS, HR 1.52), and HLH (HR 1.99) were associated with a higher risk of herpesviruses. Independent predictors of fungal infections included prior HCT (HR 1.59), CRS (HR 1.58) and hypogammaglobulinemia (HR 1.40). Idecabtagene vicleucel was associated with a lower risk of herpesvirus and fungal infections (HR 0.39 and 0.44, respectively). ConclusionsIn a large cohort of CAR T-cell therapy recipients, respiratory viral infections were the most common but occurred later, while herpesvirus and fungal infections were less frequent but occurred earlier. Prospective studies investigating prophylaxis and pre-emptive monitoring strategies are needed in this population.

Rhythm and rate control strategies in patients with long-standing persistent atrial fibrillation treated with cardiac resynchronization: the results of the randomized Pilot-CRAfT study.

Atrial fibrillation (AF) is common in cardiac resynchronization therapy (CRT) recipients. It is a marker of impaired CRT response mainly mediated by the reduction of effectively captured biventricular paced beats (BiVp). There are no randomized trials comparing strategies to maintain high BiVp percentage. To compare the efficacy of rhythm vs rate control strategies in CRT recipients with long-standing persistent AF. We performed a randomized trial including CRT recipients with persistent AF resulting in low BiVp%. All patients received amiodarone, the rhythm control group received external electrical cardioversion (EC), and the rate control group received atrioventricular node ablation, if needed. The primary end-point was 12-month BiVp% (NCT). 43 patients were included in the analysis. The mean age was 68.4 (SD: ± 8.3) years and the mean BiVp% 82.4% ± 9.7%. AF lasted 25 ± 19 months. The mean baseline left ventricular ejection fraction (LVEF), left atrium area, and the maximal oxygen uptake (VO2max) were: 30 ± 8%, 33 ± 7 cm2, and 14 ± 5 mL/(kg*min), respectively. The EC success rate was 58%. 38% patients remained in sinus rhythm (SR) after 12 months. BiVp% increased similarly in both arms reaching 99% [95% CI 97.3-99.8] and 98% [94.0-99.0], P = 0.14 in rhythm and rate control groups, respectively. LVEF raised significantly only in the rhythm control group (ΔLVEF 4.1 (± 7.3), P = 0,018) which was driven by the patients who maintained SR. No differences in VO2max, QoL, clinical and safety end-points were observed. Despite comparable BiVp% in both groups, only restoration of SR led to improved left ventricular ejection fraction in CRT patients with long-standing AF. NCT01850277 registered on 22/04/2013.

Chimeric antigen receptor-T-cell therapies going viral: latent and incidental viral infections.

Infections are the leading cause of non-relapse mortality following chimeric antigen receptor (CAR)-T-cell therapy, with viral infections being frequent both in the early and late phases post-infusion. We review the epidemiology of viral infections and discuss critical approaches to prevention and management strategies in this setting. Herpesviruses dominate the early period. herpes simplex virus and varicella zoster virus infections are rare due to widespread antiviral prophylaxis, but cytomegalovirus (CMV) reactivation is increasingly observed, particularly in high-risk groups including B cell maturation antigen (BCMA)-CAR-T-cell therapy recipients and patients receiving corticosteroids. While CMV end-organ disease is rare, CMV is associated with increased mortality, emphasizing the need to evaluate the broader impact of CMV on long-term hematological, infection, and survival outcomes. Human herpesvirus-6 (HHV-6) has also emerged as a concern, with its diagnosis complicated by overlapping symptoms with neurotoxicity, underscoring the importance of considering viral encephalitis in differential diagnoses. Respiratory viruses are the most common late infections with a higher incidence after BCMA CAR-T-cell therapy. Vaccination remains a critical preventive measure against respiratory viruses but may be less immunogenic following CAR-T-cell therapy. The optimal timing, type of vaccine, and dosing schedule require further investigation. A better understanding of viral epidemiology and preventive trials are needed to improve infection prevention practices and outcomes following CAR-T-cell therapies.

Mid-term clinical outcomes and cardiac function in patients receiving cardiac contractility modulation.

To describe the mid-term clinical and functional cardiac contractility modulation therapy (CCM) recipients in an urban population with heart failure. CCM is a non-excitatory electrical therapy for patients with systolic heart failure with NYHA class III symptoms and ejection fraction (EF) 25-45%. How CCM affects a broad range of clinical measures, including diastolic dysfunction (DD) and weight change, is unexplored. We reviewed 31 consecutive patients at our center who underwent CCM implant. NYHA class, hospitalizations, ejection fraction (EF), diastolic function, and weight were compared pre- and post-CCM implant. Mean age and follow-up time was 63 ± 10years and 1.4 ± 0.8years, respectively. Mean NYHA class improved by 0.97 functional classes (p < 0.001), and improvement occurred in 68% of patients. Mean annualized hospitalizations improved (0.8 ± 0.8 vs. 0.4 ± 1.0 hospitalizations/year, p = 0.048), and after exclusion of a single outlier, change in annualized days hospitalized also improved (total cohort 3.8 ± 4.7 vs. 3.7 ± 14.8days/year; p = 0.96; after exclusion, 3.8 ± 4.7 vs. 1.1 ± 1.9days/year, p < 0.001). Mean EF improved by 8% (p = 0.002), and among those with DD pre-CCM, mean DD improvement was 0.8 "grades" (p < 0.001). Mean weight change was 8.5 pounds lost, amounting to 4% of body weight (p = 0.002, p = 0.002, respectively), with 77% of patients having lost weight after CCM. Five patients (16%) experienced procedural complications; incidence skewed toward early implants. In an observational cohort, CCM therapy resulted in improvement in NYHA class, hospitalizations, systolic and diastolic function, and weight.

Perioperative Use of IgM-Enriched Immunoglobulins in Liver Transplantation Recipients at High Risk for Infections: A Preliminary Study.

Background: Infections frequently occur after orthotopic liver transplantation (OLT) and are associated with increased mortality. In 2018, we introduced perioperative administration of intravenous immunoglobulin enriched in IgM as an optional therapy in recipients at a high risk of infection. This preliminary study evaluated whether this preparation reduced infections in the early post-transplantation period. Methods: Adult patients with a high risk of postoperative infections who underwent OLT between January 2014 and December 2021 in our center were included in the study. The primary outcome was the occurrence of new postoperative bacterial and fungal infections within the first 30 days after OLT. Results: Ninety recipients at a high risk of postoperative infections who underwent OLT were included, of whom 51 (57%) received IgM preparation. Patients treated and not treated with IgM were similar in terms of demographics, model of end-stage liver disease score, and risk factors for postoperative infections. The occurrence of new infections was lower (absolute risk reduction (ARR) 21.2%; p = 0.038) in patients who received IgM than in those who did not. Multivariate analysis adjusted for confounders (OR 0.348; p = 0.033) and propensity score-based matching analysis (ARR 21.2%, p = 0.067) confirmed an association between IgM preparation and lower occurrence of postoperative infections. The 90-day mortality rate was lower (ARR 13.4%, p = 0.018) in patients who received IgM preparation. Conclusions: In OLT recipients at high risk for infections, perioperative administration of an IgM-enriched preparation seems to reduce the development of new infections within the first 30 days after OLT.

Risk Factors and Outcomes of Mucorales Infection in a Modern Cohort of Solid Organ Transplant, Hematopoietic Cell Transplant, and Chimeric Antigen Receptor T-cell Therapy Recipients

Mucorales infections continue to cause significant morbidity and mortality in immunocompromised hosts despite the advent of new approaches for diagnosis and treatment of fungal infections. We aimed to evaluate risk factors and outcomes of Mucorales infection in solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell therapy recipients. This single-center retrospective study included solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell patients with cultures positive for Mucorales. Forty-three patients were included for analysis; 34 solid organ transplant (79%) and 9 hematopoietic stem cell transplant or chimeric antigen receptor T-cell (21%). Infection with Mucorales occurred a median of 184 days after transplant. At the time of diagnosis, 36 patients were on antifungal prophylaxis with the majority receiving posaconazole (53%). Thirty-three had clinically significant disease; 30 received definitive anti-Mucorales therapy and 3 empiric antifungal therapy. Isavuconazole was the most common azole used for treatment in monotherapy recipients. All-cause mortality was 64% and, of these deaths, 18 (75%) were directly related to Mucormycosis. The highest mortality was seen in disseminated and intra-abdominal disease (100%), followed by pulmonary disease (50%). There was no significant association with mortality and transplant type or number of immunosuppressive agents. Mucormycosis is an important cause of morbidity and mortality in immunocompromised patients. Breakthrough infection was not uncommon in this study. Data regarding the incidence of infection at approximately 6 months after transplantation can inform prophylaxis and treatment regimens. The spectrum of antifungal regimens used reflects the lack of consensus on ideal regimens for these organisms and a need for more studies.

Protein Intake and Mortality in Older Adults With Chronic Kidney Disease

Avoiding high protein intake in older adults with chronic kidney disease (CKD) may reduce the risk of kidney function decline, but whether it can be suboptimal for survival is not well known. To estimate the associations of total, animal, and plant protein intake with all-cause mortality in older adults with mild or moderate CKD and compare the results to those of older persons without CKD. Data from 3 cohorts (Study on Cardiovascular Health, Nutrition and Frailty in Older Adults in Spain 1 and 2 and the Swedish National Study on Aging and Care in Kungsholmen [in Sweden]) composed of community-dwelling adults 60 years or older were used. Participants were recruited between March 2001 and June 2017 and followed up for mortality from December 2021 to January 2024. Those with no information on diet or mortality, with CKD stages 4 or 5, or undergoing kidney replacement therapy and kidney transplant recipients were excluded. Data were originally analyzed from June 2023 to February 2024 and reanalyzed in May 2024. Cumulative protein intake, estimated via validated dietary histories and food frequency questionnaires. The study outcome was 10-year all-cause mortality, ascertained with national death registers. Chronic kidney disease was ascertained according to estimated glomerular filtration rates, urine albumin excretion, and diagnoses from medical records. The study sample consisted of 8543 participants and 14 399 observations. Of the 4789 observations with CKD stages 1 to 3, 2726 (56.9%) corresponded to female sex, and mean (SD) age was 78.0 (7.2) years. During the follow-up period, 1468 deaths were recorded. Higher total protein intake was associated with lower mortality among participants with CKD; adjusted hazard ratio (HR) for 1.00 vs 0.80 g/kg/d was 0.88 (95% CI, 0.79-0.98); for 1.20 vs 0.80 g/kg/d, 0.79 (95% CI, 0.66-0.95); and for 1.40 vs 0.80 g/kg/d, 0.73 (95% CI, 0.57-0.92). Associations with mortality were comparable for plant and animal protein (HRs, 0.80 [95% CI, 0.65-0.98] and 0.88 [95% CI, 0.81-0.95] per 0.20-g/kg/d increment, respectively) and for total protein intake in participants younger than 75 years vs 75 years or older (HRs, 0.94 [95% CI, 0.85-1.04] and 0.91 [95% CI, 0.85-0.98] per 0.20-g/kg/d increment in total protein intake, respectively). However, the hazards were lower among participants without CKD than in those with CKD (HRs, 0.85 [95% CI, 0.79-0.92] and 0.92 [95% CI, 0.86-0.98] per 0.20-g/kg/d increment, respectively; P = .02 for interaction). In this multicohort study of older adults, higher intake of total, animal, and plant protein was associated with lower mortality in participants with CKD. Associations were stronger in those without CKD, suggesting that the benefits of proteins may outweigh the downsides in older adults with mild or moderate CKD.

Treatment Patterns and Preferences for Graves' Disease in Korea: Insights from a Nationwide Cohort Study.

Treatment patterns and preferences for patients with Graves' disease (GD) vary across countries. In this study, we assessed the initial therapies and subsequent treatment modalities employed for GD in real-world clinical practice in Korea. We analyzed 452,001 patients with GD from 2004 to 2020, obtained from the Korean National Health Insurance Service database. Initial treatments included antithyroid drug (ATD) therapy (98% of cases), thyroidectomy (1.3%), and radioactive iodine (RAI) therapy (0.7%). The rates of initial treatment failure were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Even among cases of ATD treatment failure or recurrence, the rates of RAI therapy remained low. Regarding initial treatment, the 5-year remission rate was 46.8% among patients administered ATDs versus 91.0% among recipients of RAI therapy; at 10 years, these rates were 59.2% and 94.0%, respectively. Our findings highlight a marked disparity in the use of RAI therapy in Korea compared to Western countries. Further research is required to understand the reasons for these differences in treatment patterns.

Fragmentation of care in breast cancer: greater than the sum of its parts

IntroductionFragmentation of care (FC, the receipt of care at > 1 institution) has been shown to negatively impact cancer outcomes. Given the multimodal nature of breast cancer treatment, we sought to identify factors associated with FC and its effects on survival of breast cancer patients.MethodsA retrospective analysis was performed of surgically treated, stage I–III breast cancer patients in the 2004–2020 National Cancer Database, excluding neoadjuvant therapy recipients. Patients were stratified into two groups: FC or non-FC care. Treatment delay was defined as definitive surgery > 60 days after diagnosis. Multivariable logistic regression was performed to identify factors predictive of FC, and survival was compared using Kaplan–Meier and multivariable Cox proportional hazards methods.ResultsOf the 531,644 patients identified, 340,297 (64.0%) received FC. After adjustment, FC (OR 1.27, 95% CI 1.25–1.29) was independently associated with treatment delay. Factors predictive of FC included Hispanic ethnicity (OR 1.04, 95% CI: 1.01–1.07), treatment at comprehensive community cancer programs (OR 1.06, 95% CI: 1.03–1.08) and integrated network cancer programs (OR 1.55, 95% CI: 1.51–1.59), AJCC stage II (OR 1.06, 95% CI 1.05–1.07) and stage III tumors (OR 1.06, 95% CI: 1.02–1.10), and HR + /HER2 + tumors (OR 1.05, 95% CI: 1.02–1.07). Treatment delay was independently associated with increased risk of mortality (HR 1.23, 95% CI 1.20–1.26), whereas FC (HR 0.87, 95% CI 0.86–0.88) showed survival benefit.ConclusionsWhile treatment delay negatively impacts survival in breast cancer patients, our findings suggest FC could be a marker for multispecialty care that may mitigate some of these effects.

Procalcitonin level threshold and antibiotic use in patients receiving chimeric antigen receptor T-cell therapy

ABSTRACT Background: Patients undergoing chimeric antigen receptor (CAR) T-cell therapy are vulnerable to infection and sepsis. Treatment course is frequently complicated by cytokine release syndrome which is often clinically and biochemically indistinguishable from sepsis. Procalcitonin (PCT) levels have been examined as a promising biomarker for infection in this cohort of patients. Methods: In this study, we measured daily PCT levels for patients for fourteen days (or hospital discharge) after receiving CAR T-cells to determine threshold PCT values specific for infection compared to those without infection. Results: We present preliminary results of our enrolled cohort to date (sixteen patients). Infection was present in only 12.5% of patients. However, those diagnosed with sepsis had elevated PCT levels with a peak mean of 2.6 µg/L observed on the seventh day post-treatment compared to those without infection remaining below 0.5 µg/L. Furthermore, we observed a trend for early and liberal antibiotic administration within our cohort. Conclusion: Our study highlights the challenges of antimicrobial stewardship in managing CAR T-cell therapy recipients. Our preliminary results underscore the utility of PCT in the risk-stratification and diagnosis of those patients at high risk for infectious complications after receiving CAR T-cell therapy and continue to advocate for a PCT threshold of 1.5 µg/L for diagnosing sepsis. Additionally, in the setting of CRS and lymphodepletion, where white cell count and CRP value are unreliable, a PCT value of < 0.5 µg/L may help exclude sepsis.

Cytomegaloviral Infections in Recipients of Chimeric Antigen Receptor T-Cell Therapy: An Observational Study With Focus on Oncologic Outcomes.

Patients with B-cell lymphoma and acute lymphoblastic leukemia (ALL) who receive chimeric antigen receptor T-cell (CAR-T) therapy may experience clinically significant cytomegalovirus infection (CS-CMVi). However, risk factors for CS-CMVi are not well defined. The aims of our study were to identify risk factors for CS-CMVi and the association between CS-CMVi and nonrelapse mortality (NRM) in lymphoma and ALL patients after CAR-T therapy. We performed a retrospective single-center cohort analysis of CAR-T recipients between January 2018 and February 2021 for treatment of lymphoma and ALL. We collected data on demographics, oncologic history, CAR-T therapy-related complications, and infectious complications within 1 year of therapy. Of 230 patients identified, 22 (10%) had CS-CMVi. At 1 year following CAR-T therapy, 75 patients (33%) developed relapsed disease and 95 (41%) died; NRM at 1 year was 37%. On Cox regression analysis, Asian or Middle Eastern race (adjusted hazard ratio [aHR], 13.71 [95% confidence interval {CI}, 5.41-34.74]), treatment of cytokine release syndrome/immune effector cell-associated neurotoxicity syndrome with steroids (aHR, 6.25 [95% CI, 1.82-21.47]), lactate dehydrogenase at time of CAR-T therapy (aHR, 1.09 [95% CI, 1.02-1.16]), and CMV surveillance (aHR, 6.91 [95% CI, 2.77-17.25]) were independently associated with CS-CMVi. CS-CMVi was independently associated with NRM at 1 year after CAR-T therapy (odds ratio, 2.49 [95% CI, 1.29-4.82]). Further studies of immunologic correlatives and clinical trials to determine the efficacy of prophylactic strategies are needed to understand the role of CS-CMVi and post-CAR-T mortality.

The Effect of Sleep Habits on Quality of Life in Pediatric Patients With Chronic Kidney Disease.

Sleep disturbance has been studied in adult patients with early and end-stage chronic kidney disease (CKD). However, there are limited publications on the pediatric patient population. This paper evaluated the association between sleep disturbances and quality of life (QoL) inpediatricpatients with CKD. The study included 22 patients and 22 healthy controls from the pediatric nephrology outpatient clinic.All participants completed the Turkish Generic Health-Related Quality of Life Questionnaire for Children and Adolescents (HRQoLQ) and the Child Sleep Habits Questionnaire(CSHQ). Patients diagnosed with CKD were compared in terms of HRQoLQ and CSHQ scores within themselves as kidney replacement therapy (KRT) recipients and non-recipients and with the control group. The mean HRQoLQ total score of the patients was 89.0 ± 12.4 and the mean CSHQ total score was 46.7 ± 5.6; there was no correlation between the total scores (p=0.599). CSHQ total and subgroup scores were similar in patients with and without KRT. The CSHQ total and subgroup median scores were not different in the patient and control groups. According to the HRQoL scale, the total QoL score and the physical and emotional well-being subscale scores were lower in patients receiving KRT than in those not receiving KRT. Sleep problems and HRQoL should not be underestimated in the pediatric CKD population, especially in patients receiving KRT. Large-scale studies with long-term outcomes are needed to understand better and improve QoL.

M146 - Effectiveness of Family Intervention Addressing Expressed Emotions in Recipients of Opioid Substitution Therapy: A Randomised Controlled Study

M146 - Effectiveness of Family Intervention Addressing Expressed Emotions in Recipients of Opioid Substitution Therapy: A Randomised Controlled Study

Effect of Medical Ozone Therapy in Preventing Compromised Nasal Skin in Revision Rhinoplasty.

Ozone is often used as an additive therapy for skin conditions like infectious diseases, wound healing, diabetic foot, and pressure ulcers. The viability of the nasal skin has crucial importance in revision rhinoplasty cases. The study investigates the potential benefits of medical ozone therapy in healing the nasal skin in multiple-operated cases. The study retrospectively examined 523 revision rhinoplasty patients operated by the first author from January 2017 to January 2024. Patients consenting to ozone therapy received 3 major autohemotherapy sessions post-surgery. Patients were divided into 2 groups: those with compromised nasal skin (infection, poor vascular supply) and those with normal healing. Age, gender, smoking, diabetes, previous surgeries, grafting materials, and techniques were considered. Of the 523 patients, 12 (2.3%) experienced major skin complications like infection and necrosis, while 511 (97.7%) had no or minor issues, such as discoloration. In total, 301 patients accepted and received ozone therapy. Of the patients without major complications, 299 (58.3%) received ozone therapy, while 212 (41.7%) did not. Among the 12 with major complications, two (16.7%) received ozone therapy, and the remaining 10 (83.3%) did not. Ozone therapy recipients showed statistically fewer skin problems (p<0.05). Costal cartilage as tip and septal extension graft was linked to skin issues (p<0.05). No major adverse effects from ozone therapy were noted. Our findings indicate that ozone therapy may be a safe and potentially effective option for patients undergoing revision rhinoplasty, especially those with compromised nasal skin. It appears to aid in skin healing and regeneration, possibly through enhancing oxygen delivery and modulation of the immune response. Ozone therapy is a promising adjunct treatment for managing skin complications in revision rhinoplasty patients. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Overview of infectious complications among CAR T- cell therapy recipients.

Chimeric antigen receptor-modified T cell (CAR T-cell) therapy has revolutionized the management of hematological malignancies. In addition to impressive malignancy-related outcomes, CAR T-cell therapy has significant toxicity-related adverse events, including cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), immune effector cell-associated hematotoxicity (ICAHT), and opportunistic infections. Different CAR T-cell targets have different epidemiology and risk factors for infection, and these targets result in different long-term immunodeficiency states due to their distinct on-target and off- tumor effects. These effects are exacerbated by the use of multimodal immunosuppression in the management of CRS and ICANS. The most effective course of action for managing infectious complications involves determining screening, prophylactic, and monitoring strategies and understanding the role of immunoglobulin replacement and re-vaccination strategies. This involves considering the nature of prior immunomodulating therapies, underlying malignancy, the CAR T-cell target, and the development and management of related adverse events. In conclusion, we now have an increasing understanding of infection management for CAR T-cell recipients. As additional effector cells and CAR T-cell targets become available, infection management strategies will continue to evolve.

Impact of COVID-19 monoclonal antibodies on outcomes of COVID-19 infection in hematopoietic stem cell transplant and chimeric antigen receptor therapy recipients.

Hematopoietic stem cell transplant (HSCT) and chimeric antigen receptor T-cell therapy (CAR-T) recipients are at higher risk of serious complications of COVID-19 infection than the general population. Though there is evidence that monoclonal antibodies (MCA) against COVID-19 reduce the risk of death and hospitalization in the general population, data regarding their efficacy in HSCT and CAR-T recipients remains scarce. We conducted a retrospective review of HSCT and CAR-T recipients to compare 30-day outcomes between patients who did and did not receive MCA after their first episode of COVID-19 between May 1, 2020 and December 31, 2022. Outcomes were defined as the most severe complication experienced out of the following: 30-day emergency department visit, hospitalization, intensive care unit admission, and death after COVID-19 infection. We identified 166 patients comprised of 53.6% allogeneic HSCT, 35.5% autologous HSCT, and 10.8% CAR-T recipients; 107 had received a COVID-19 vaccine >2 weeks prior to testing positive, and 40 were treated with MCA. After adjusting for age, presence of symptoms at the initial positive test, and COVID-19 vaccination status, patients who did not receive MCA were five times more likely to develop complications after COVID-19 infection (adjusted odds ratio 5.0 [95% CI, 1.9-12.8], p =.001). HSCT and CAR-T recipients who received MCA following COVID-19 infection were far less likely to develop COVID-related complications than those who did not receive MCA, regardless of vaccination status. This underscores the potential benefit of developing novel MCA with efficacy against circulating COVID-19 strains.

Omicron SARS-CoV-2 infection management and outcomes in patients with hematologic disease and recipients of cell therapy.

Scarce real-life data exists for COVID-19 management in hematologic disease (HD) patients in the Omicron era. To assess the current clinical management and outcome of SARS-CoV-2 infection diagnosed, identify the risk factors for severe outcomes according to the HD characteristics and cell therapy procedures in a real-world setting. A retrospective observational registry led by the Spanish Transplant Group (GETH-TC) with 692 consecutive patients with HD from December 2021 to May 2023 was analyzed. Nearly one-third of patients (31%) remained untreated and presented low COVID-19-related mortality (0.9%). Nirmatrelvir/ritonavir was used mainly in mild COVID-19 cases in the outpatient setting (32%) with a low mortality (1%), while treatment with remdesivir was preferentially administered in moderate-to-severe SARS-CoV-2 infection cases during hospitalization (35%) with a mortality rate of 8.6%. The hospital admission rate was 23%, while 18% developed pneumonia. COVID-19-related mortality in admitted patients was 14%. Older age, autologous hematopoietic stem cell transplantation (SCT), chimeric antigen receptor T-cell therapy, corticosteroids and incomplete vaccination were factors independently associated with COVID-19 severity and significantly related with higher rates of hospital admission and pneumonia. Incomplete vaccination status, treatment with prior anti-CD20 monoclonal antibodies, and comorbid cardiomyopathy were identified as independent risk factors for COVID-19 mortality. The results support that, albeit to a lower extent, COVID-19 in the Omicron era remains a significant problem in HD patients. Complete vaccination (3 doses) should be prioritized in these immunocompromised patients. The identified risk factors may help to improve COVID-19 management to decrease the rate of severe disease, ICU admissions and mortality.

Clinical Impact of Digitalis Therapy in a Large Multicenter Cohort of CRT-Recipients.

(1) Introduction: Digitalis use in patients with severe heart failure is controversial. We assessed the effects of digitalis therapy on mortality in a large, observational study in recipients of cardiac resynchronization therapy (CRT). (2) Methods: Consecutive patients receiving a CRT-defibrillator in three European tertiary referral centers were enrolled and followed-up for a mean 37 months ± 28 months. Digitalis use was assessed at the time of CRT implantation. A multivariate Cox-regression model and propensity score matching were used to determine all-cause mortality as the primary endpoint. CRT-response (defined as improvement of ≥1 NYHA class), echocardiographic improvement (defined as improvement of LVEF of ≥ 5%) and incidence of ICD shocks and rehospitalization were assessed as secondary endpoints in a subgroup of patients. (3) Results: The study comprised 552 CRT-recipients with standard indications, including 219 patients (40%) treated with digitalis. Compared to patients without digitalis, they had more often atrial fibrillation, poorer LVEF and a higher NYHA class (all p ≤ 0.002). Crude analysis of all-cause mortality demonstrated a similar relative risk of death for patients with and without digitalis (HR = 1.14; 95% CI 0.88-1.5; p = 0.40). After adjustment for independent predictors of mortality, digitalis therapy did not alter the risk for death (adjusted HR = 1.04; 95% CI 0.75-1.45; p = 0.82). Furthermore, in comparison to 286 propensity-score-matched patients, mortality was not affected by digitalis intake (propensity-adjusted HR = 1.11; 95% CI 0.72-1.70; p = 0.64). A CRT-response was predominant in digitalis non-users, concerning both improvement of HF symptoms and LVEF (NYHA p < 0.01; LVEF p < 0.01), while patients on digitalis had more often ventricular tachyarrhythmias requiring ICD shock (p = 0.01); although, rehospitalization for cardiac reasons was significantly lower among digitalis users compared to digitalis non-users (HR = 0.58; 95% C. I. 0.40-0.85; p = 0.01). (4) Conclusions: Digitalis therapy had no effect on mortality, but was associated with a reduced response to CRT and increased susceptibility to ventricular arrhythmias requiring ICD shock treatment. Although, digitalis administration positively altered the likelihood for cardiac rehospitalization during follow-up.

Cardiomyopathy among recipients of immune checkpoint inhibitor therapy: A prospective study.

e24025 Background: Patients treated with immune checkpoint inhibitors (ICI) may develop cardiomyopathy, but data are limited on the rate of cardiomyopathy incidence. The aim of this study was to assess the occurrence of cardiomyopathy among ICI recipients. Methods: In this prospective surveillance study, echocardiograms and EKG were performed at baseline, and quarterly during the first year of ICI therapy. New or worsening cardiomyopathy was defined as left ventricular ejection fraction (EF) decline of &gt; 10% from baseline to &lt; 50%. B-type natriuretic peptide (BNP) and troponin were assessed weekly during the first three weeks of ICI therapy. Subsequent troponin for myocarditis assessment was tested as needed per treating oncology team. Results: A total of 23 patients were enrolled with mean age 73±10 years, 35% female, 74% Caucasian, and body mass index 31±7 kg/m2. Cardiovascular risk factors included hypertension (86%), diabetes mellitus (29%), myocardial infarction (19%) and smoking (10%), and prior radiation treatment (30%). Malignancies included lung cancer (50%), renal cell carcinoma (14%), and Merkel cell carcinoma or urothelial carcinoma (9% each). ICI regimen included pembrolizumab (48%), nivolumab (43%), and ipilimumab or atezolizumab (4% each). There was no change in weekly troponin or BNP, or quarterly QRS duration on EKG, and no myocarditis cases were observed. Between baseline and at 1-year since ICI therapy initiation, there was no change in QRS duration on EKG, as well as no change in median LVEF (59% [IQR 46-67] vs 61% [IQR 58-65], p = 0.48), or global longitudinal strain (18% [IQR 15-20]) vs 19% [IQR 18-21], p = 0.11). New cardiomyopathy occurred in 1 (4%) patient at 3 months following ICI initiation with LVEF drop from 53% to 38% and without troponin elevation to suggest myocarditis, corresponding to an incidence rate of 43.5 cases per 1000 person-years of observation. Conclusions: In this prospective surveillance study, new cardiomyopathy was observed after ICI treatment, although the incidence was low. Larger studies are needed to confirm these findings.