Citations

Abstract Background Babesia and Plasmodium are intraerythrocytic parasites that cause babesiosis and malaria, respectively. Significant associations between human blood group antigens and malaria are known; however, few studies have examined the relationship between blood group antigens and babesiosis. Study Design and Methods From June to August 2025, 100 Babesia polymerase chain reaction (PCR)− and 100 B. microti PCR+ human patient samples tested at a national reference laboratory underwent ABO and D phenotyping and red blood cell (RBC) genotyping of 37 antigens. Results The predicted phenotype of S‐s+ was found in 32% and 50% of Babesia − and B. microti + patients, respectively (χ 2 = 5.97, p = .015, odds ratio = 2.125, 95% confidence interval 1.18–3.78). Two B. microti + patients had the predicted phenotype of Fy(a‐b‐), meaning that Duffy is unlikely to be an essential invasion receptor. There were no statistically significant differences in ABO or D expression between the groups. Discussion Because multiple testing corrections were not applied to the statistical analyses, the S/s predicted phenotype results must be viewed as hypothesis‐generating. This may be the first study to link B. microti infection to human RBC S/s antigens, which are known to impact B. divergens and P. falciparum . Additional studies are needed to understand the impact of the babesiosis patient's blood type on B. microti infection and whether the transfusion of RBCs expressing specific antigens can impact the disease.

ABSTRACT Talquetamab is a GPRC5D × CD3 bispecific antibody approved for relapsed/refractory multiple myeloma (RRMM). This is the first real‐world study to comprehensively report muco‐cutaneous toxicities, infections, and efficacy of talquetamab in 151 patients across five countries with the longest follow‐up reported enabling better efficacy and toxicity estimates. The median age was 64 years; high‐risk cytogenetics were present in 42%; ECOG ≥ 2 in 22%; 12% had creatinine clearance < 30; and 55% would not have met MonumenTAL‐1 eligibility. Patients received a median of 6 prior lines of therapy, 53% were penta‐refractory, and 75% received prior BCMA therapy. Talquetamab was associated with skin toxicity in 39.7%, nail toxicity in 75.5%, dysgeusia in 60.4%, and oral toxicities in 62.9%, with grade ≥ 3 events uncommon (≤ 4%) and dose interruptions infrequent (9.6% for skin toxicity, 6.9% for dysgeusia, and 4.0% for oral toxicities). These findings underscore the need for improved supportive care for muco‐cutaneous toxicities. In multivariate analysis, only platelet count < 50 (HR 1.8, 95% CI 1.15–2.83) was associated with inferior PFS, while penta‐refractory status, absolute lymphocyte count < 0.4, and prior BCMA‐targeted therapy were not statistically significant. With a median follow‐up of 12.7 months, the overall response rate was 67.6%, median progression‐free survival was 7 months, and 12‐month overall survival was 65%. This study shows that talquetamab efficacy is maintained in a heavily pretreated real‐world population with high prior BCMA exposure and notable comorbidity burden.

ABSTRACT Age‐related changes in human hematopoietic stem cells (HSCs) often form the basis for clonal hematopoiesis (CH), which presages the development of overt myeloid neoplasm with variable risk. CH can also arise after exposure to chemotherapy, radiotherapy, or immune interventions. In this study, we performed clinico‐genomic profiling of therapy‐related CH (t‐CH) ( n = 67) versus de novo CH ( n = 123) from a multidisciplinary CHIP Clinic. The most enriched mutations in t‐CH were TET2 (26.2%), DNMT3A (22.4%), and TP53 (8.4%). Median latency period from the time of initial exposure to the diagnosis of t‐CH was 6.96 ± 1.10 years. Patients with t‐CH had inferior event‐free survival compared to de novo CH (median 29.9 months versus 122.1 months, p = 0.0045). Overall survival was also shorter in t‐CH versus de novo CH (median 55.3 months vs. 129.2 months, p = 0.043). Genes that imparted significantly increased risk for progression from t‐CH to overt therapy‐related myeloid neoplasm (t‐MN) included JAK2 (relative risk (RR) 9.42, p = 0.0001), RUNX1 (RR 7.11, p = 0.001), EZH2 (RR 7.11, p = 0.001), and TET2 (RR 13.4, p = 0.01). Clonal dynamic modeling of patients with t‐CH who progressed to overt t‐MN showed an increase in the relative clonal fraction and new clonal outgrowth. In the t‐CH cohort, higher mean variant allele frequency was observed in progressors versus non‐progressors (77.1% vs. 30.6%, p = 0.017). This study sheds light onto outcomes for CH based on differing clinical ontogeny and has implications for previvorship for secondary malignancies.

Abstract The use of chimeric antigen receptor (CAR) T-cell therapy is increasing for adult B-cell acute lymphoblastic leukemia (B-ALL), with 3 CD19 CAR T-cell products commercially available. Several key clinical questions related to best practices for CAR T-cell administration in this population exist, and limited prospective randomized trials have been conducted to fill these knowledge gaps. Thus, to help guide clinical practice, we conducted a modified Delphi study to develop and validate consensus recommendations on the administration of commercially available CAR T-cell therapy for adults with B-ALL. Consensus panelists (n = 9) included principal investigators (PIs) from Real World Outcomes Collaborative of CAR T-Cell Therapy in Adult ALL (ROCCA) consortium sites and were selected based on expertise and CAR T-cell center volume. Final panel consensus recommendations were distributed for rating by the remaining PIs from ROCCA consortium sites, which served as the validation group (n = 27). Consensus topics included patient selection, bridging and pre–CAR T-cell leukemia staging, lymphodepletion, and CAR T-cell treatment setting, specific toxicity prevention and management, post–CAR T-cell response assessment and disease monitoring, and the role of consolidation and/or maintenance therapies after CAR T-cell therapy. Initially, 58 recommendation statements were evaluated for consensus. After 2 panel meetings, a total of 34 statements achieved consensus rating among the expert panel. After rating by the validation group, all but 1 recommendation statement continued to meet consensus, for a total of 33 consensus recommendation statements on the administration of CAR T-cell therapy in adult B-ALL.

Objective: To compare disease-specific quality of life (QOL) among patients with sporadic vestibular schwannoma (VS) by tumor management strategy using the recently developed and validated Mayo Clinic VSQOL Index relative to established minimal important difference (MID) thresholds. Study design: Cross-sectional cohort. Setting: Acoustic Neuroma Association and tertiary care center. Patients: Adults with sporadic VS. Interventions: Microsurgery, radiation, or observation. Main outcome measures: VSQOL Index scores were compared by tumor management strategy adjusting for age, sex, setting, tumor size at diagnosis, and duration of follow-up. Scores range from 0 to 100; higher scores indicate better QOL. Results: Of the 652 patients included, 333 (51%) were managed with microsurgery, 175 (27%) with radiation, and 144 (22%) with observation. The mean (SD) duration of follow-up was 6.2 (2.7) years. Global QOL adjusted mean scores (95% CI) differed significantly ( P <0.001) by management group: 70 (67-72) for microsurgery, 73 (70-77) for radiation, and 79 (75-83) for observation. Hearing Problems ( P <0.001), Dizziness and Imbalance ( P <0.001), Problems with Face or Eyes ( P <0.001), and Difficulty with Thinking and Memory ( P =0.03) domain scores also differed significantly by group. Pairwise comparisons that exceeded at least the lower bound of published MIDs included Global QOL scores (microsurgery versus observation) and Hearing Problems scores (microsurgery and radiation versus observation). Conclusions: At a mean follow-up of 6.2 years, several notable statistically and clinically significant differences in QOL were identified. These findings may be used to guide patient counseling regarding management options and require validation in future prospective studies.

Abstract Rationale Acute cellular rejection (ACR) within first-year post-lung transplantation has important implications for prognosis. Calcineurin inhibitors (CNI), including tacrolimus or cyclosporine, along with cell cycle inhibitors (CCI) and steroids, remain the standard immunosuppression regimen post-transplant. Although tacrolimus is used as the primary CNI, target therapeutic levels vary across recipients due to adverse effects and tolerability, sometimes requiring switching over to Cyclosporine. We hypothesized that ACR within the first year is associated with switching CNI from Tacrolimus to Cyclosporine. Methods We performed a cross-sectional study of 255 adult lung transplant recipients between June 2019 to November 2024 at Mayo Clinic, Florida. Demographics, induction regimens, CNI type and their levels (average low and high levels) were compared between the 2 groups. The institutional maintenance immunosuppression regimen is Tacrolimus, Mycophenolate Mofetil (MMF) and prednisone, but could be switched to Cyclosporine if the previous regimen is not tolerated. The primary outcome was ACR &lt;1 year diagnosed based on biopsy and/or clinical criteria. Comparisons between groups were performed using Chi-Square test for categorical variables and t-test or Wilcoxon Rank sum test for continuous variables. Multivariable regression analysis was performed with ACR &lt;1 year as the outcome to adjust for the confounders. Results Our cohort included 255 lung transplant recipients with median age of 63 years, 61% Male, 84% Caucasians, 88% bilateral lung transplant (Further details elucidated in Table 1). A total of 173 (67%) out of 255 patients had ACR &lt;1 year. The group with ACR &lt; 1 year had higher proportion of Interstitial Lung Disease (ILD) (81% vs 68%, p = 0.044), use of Basiliximab for induction (70% vs 55%, p = 0.018), and cyclosporine instead of tacrolimus (23% vs 11%, p = 0.027). Group with ACR &lt;1 year also had higher Antibody Mediated Rejection (AMR) &lt; 1year (15% vs 6.1%, p = 0.041) and higher CLAD (BOS 0p-3: 43% vs 25.6%, p = 0.033) compared to the group without ACR &lt; 1 year (Table 1.1). Multivariate regression analysis showed ILD (adjusted odds ratio, aOR 2.84, 95% CI 1.31 - 6.27, p = 0.008) and use of cyclosporine (aOR 2.55, 95% CI 1.07 - 6.78, p = 0.034) as independent predictors of ACR &lt; 1 year (Table 2). Conclusions The presence of ACR &lt; 1 year was associated with the use of Cyclosporine over Tacrolimus as a maintenance regimen. Also, ACR &lt; 1year was associated with higher AMR and CLAD. Further prospective studies are needed to study this long-term given its significant prognostic implications. This abstract is funded by: Not Applicable

Abstract Introduction Interstitial lung disease-associated pulmonary hypertension (ILD-PH) is a clinically challenging entity that lies on a pathophysiologic spectrum between pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD). We compared the metabolomes of patients with ILD-PH to those with PAH and ILD to characterize the PAH-ILD axis and determine whether ILD-PH patients can be phenotyped based on their metabolomic similarity to PAH. Methods Using untargeted metabolomics profiles from patients with PAH, ILD, and ILD-PH in the large, U.S.-based, NIH-funded, multi-center PVDOMICS cohort, we trained an anchor-based classifier on PAH and ILD metabolomes using supervised PLS-DA with a 75/25 train/test split. Primary and secondary PH or risk-group classifications in PVDOMICS were based on expert adjudication of clinical data including right heart catheterization hemodynamics, pulmonary function testing, chest imaging, and laboratory results. We then applied the trained model to each ILD-PH patient to assign a PAH similarity score. We classified patients as having a PAH-like or ILD-like metabolomic phenotype using an optimal PAH similarity score cutoff of 0.5 then compared PAH metabolomic similarity to expert-adjudicated primary and secondary WSPH classifications in PVDOMICS. We implemented FELLA, a network-based metabolomics enrichment method, to holistically characterize the biologic underpinnings of PAH, ILD-PH, and ILD metabolomes. Results We analyzed 244 patients with PAH, 54 with ILD, and 47 with ILD-PH. The anchor-based classifier demonstrated high train-test performance with a c-statistic of 0.81 and 78% agreement with expert-adjudicated diagnoses. Among the ILD-PH patients, 23 were classified as PAH-like and 24 as ILD-like (74% agreement with expert adjudication, Cohen’s kappa 0.49, Hedge’s g estimate of 0.86). FELLA enrichment revealed core glycolytic and bioenergetic pathways were enriched in both pure PAH and ILD-PH. Comparison of diffusion Z-scores between groups demonstrated subtle but biologically coherent differences in several reaction-level nodes, including lactate, NADPH oxidoreductase, and phosphofructokinase, which were enriched in ILD-PH. Conclusion Patients with ILD-PH demonstrate clinically relevant metabolomic phenotypes. Examination of the network biology underlying ILD-PH may point to potential therapeutic targets in this vulnerable subgroup with lagging clinical outcomes. This abstract is funded by: Pulmonary Fibrosis Foundation PFF Scholars Program

Abstract Rationale American Indians and Alaska Native (AI/AN) people have the highest prevalence of tobacco use of any US racial or ethnic minoritized group, though this varies regionally. Smoking, and smoking-related cancers including lung cancer are more common in AI/AN people than non-Hispanic whites in the Pacific Northwest. Lung cancer screening (LCS) is effective but broadly under-utilized in AI/AN eligible adults. This study’s objective was to evaluate a AI/AN community co-designed patient navigation intervention to bridge community healthcare settings to a LDCT-capable LCS program. Methods We conducted a single-arm pilot study of the patient navigation intervention, grounded in community-based participatory research principles. The intervention was formalized in a living handbook, co-created with input from patients and providers at an AI/AN Urban Indian Organization and primary care clinic, Seattle Indian Health Board. Two community health workers served as navigators to deliver culturally sensitive support, link to shared decision-making with a nurse practitioner at the academic LCS program, coordinate transportation, interface with insurance and provide other barrier-directed activities. Patients eligible for LCS (n = 44) were recruited from the AI/AN clinic setting through on-site outreach. Enrolled participants completed pre-navigation surveys which assessed baseline knowledge, attitudes, experiences and barriers. Those who engaged with the central program completed an additional post-navigation survey (n = 15). Electronic health records were reviewed for all navigation and LCS-related data. Results Between July 2023 - November 2024, 44 participants were enrolled in the study. The median age of the participants was 65 (IQR 58-70), 66% reported current smoking, and 76% reported an annual household income &lt;$30,000. All participants reported at least one barrier that delayed care in the past 12 months. On review, two participants were up-to-date on LCS prior to enrollment. Within 6 months, 13 participants completed a shared decision-making appointment and 11 went forward with LDCT. On post-intervention surveys, barriers most commonly addressed were: scheduling (100%), transportation (80%), explaining LCS (80%) and cost/insurance (73%). Participants reported high acceptability, measured by Acceptability of Intervention Measure (AIM median 5.0, IQR 5-5) and patient satisfaction measured by Patient Navigation Satisfaction Measured-Instrument (PNS-I median 45, IQR 42-45). Conclusion A culturally tailored patient navigation program for LCS was feasible and highly acceptable among urban AI/AN adults. Navigation addressed multiple barriers and successfully connected some patient participants from a community clinic to tertiary screening centers for shared decision-making and/or screening. These findings support the effectiveness of academic-community partnered navigation to increase LCS uptake in AI/AN clinic settings. This abstract is funded by: ATS/ALA/Chest Foundation: Respiratory Health Equity Research Award (Triplette)

Abstract Rationale Lymphangioleiomyomatosis (LAM) is a rare, progressive, cystic lung disease affecting women. Sirolimus has been shown to stabilize lung function in women with LAM, but real-world data on long-term safety and efficacy are limited. Methods The NIH Multicenter Safety and Durability of Sirolimus for LAM (MIDAS, NCT02432560) observational registry was launched in 2015. All adult (≥18 years) women with LAM (treated or untreated) were eligible to enroll at any of the 20 U.S. sites and followed longitudinally with serial assessments of lung function, health-related quality of life, and treatment related adverse event (TRAEs). Baseline cohort characteristics and TRAEs are summarized using descriptive analyses. Marginal structural models (MSMs) with inverse probability of treatment weighting estimated the causal effect of sirolimus on annualized forced expiratory volume in one-second (FEV1) decline, adjusting for age at LAM diagnosis, prior treatment with sirolimus, menopausal status, race, presence of angiomyolipomas, supplemental oxygen use; time-varying covariates included diffusing capacity for carbon monoxide (DLCO) and serum vascular endothelial growth factor-D (VEGF-D) levels. Results Longitudinal data was available in 350 LAM patients, most of whom (246, 70.3%) had sporadic LAM. The median age at the baseline pulmonary function test (PFT) measurement was 46 years (range: 19 - 74) and the median (IQR) number of serial PFTs obtained per patient was 3 (1 - 5). The average follow-up duration per patient was 2.8 years. Over half of the patients (196, 56%) were treated with sirolimus during the MIDAS observation period for a median (IQR) treatment duration of 4.9 (2.4 - 7.5) years. MSM analysis demonstrated that sirolimus treatment was durably effective and reduced FEV₁ decline by 74.36 mL/year (95% CI: 15.87 - 132.85) compared with no treatment (-85.31 mL/year for the untreated group vs. -10.95 mL/year for the treated group, p = 0.01). Sirolimus was generally well tolerated; treatment interruption ≥3 months was observed in 38 (19.4%) of the 196 sirolimus treated patients. Logistic regression analysis showed that higher levels of FEV1 (odds ratio: OR = 3.12 [1.45 - 7.11], p = 0.005), VEGF-D (OR = 1.0007 [1.0004 - 1.001], p &lt; 0.001), and DLCO (OR = 1.023 [1.0053 - 1.0413, p = 0.01]), were associated with treatment interruption. Conclusions In the MIDAS cohort, sirolimus treatment resulted in durable stabilization of lung function with a favorable safety profile over a 5-year period. These real-world data support sirolimus as a chronic suppressive therapy for LAM, demonstrating durable efficacy in slowing lung disease progression and tolerability with long-term use. This abstract is funded by: National Institutes of Health