Citations

Abstract Introduction: CLL disease control and survival outcomes have improved since the introduction of Bruton tyrosine kinase inhibitors (BTKis). Since CLL often requires treatments, understanding patient preferences is critical in optimizing adherence and overall satisfaction. However, there are limited published data on how Korean patients prioritize treatment efficacy, safety and the convenience of administration. To address this gap, a discrete choice experiment (DCE) methodology was applied in a comprehensive quantitative analysis to evaluate patient preferences for BTKi treatment attributes among patients with CLL in Korea. Methods: Adult patients (≥18 years of age) with a confirmed diagnosis of CLL in Korea were recruited by The Korea Blood Disease & Cancer Association to participate in an online DCE survey questionnaire from April 30, 2025 to May 22, 2025. Treatment attributes and levels were identified based on published literature and clinical inputs. Efficacy attributes included progression-free survival (PFS); safety attributes included impacts of adverse events (AEs), including diarrhea, headache, atrial fibrillation and hypertension, on quality of life (QoL); convenience attributes included formulation type (including tablet or capsule) and dosing frequency (including once daily or twice daily). Preference data was analyzed using a conditional logistic regression. Relative importance of BTKi treatment attributes were calculated to measure the importance of each attribute in treatment decision-making. Additionally, subgroup analyses were conducted among patients aged <60 years and ≥60 years, those who received 2 or more lines (2L+) of treatments, and those who experienced AEs from CLL treatment. Results: A total of 57 patients completed the survey. The mean age was 61 years, with 46% aged <60 years and 54% aged ≥60 years. Female patients comprise 35% of the sample. Around 33% had a high school education or less, and 23% were employed full-time. More than half (54%) reported no comorbid conditions, and 70% were diagnosed ≥5 years ago (26% diagnosed 1 to <5 years ago; 4% diagnosed less than a year ago). In terms of treatment experience, 11% were treatment naive, while 89% received ≥1 treatment (61% first-line, 21% second-line and 7% third-line or later). In the context of CLL treatment preferences, patients showed a significant preference (P < .05) for therapies that minimized the impact of AEs on QoL, offered longer PFS, and required less frequent dosing. Formulation type did not have a statistically significant impact on treatment choice. Overall, patients placed greater importance on how treatment-related attributes affect their QoL and dosing frequency. The highest-ranked factors were the impact of headache (22%) and diarrhea (21%) on QoL, followed by dosing frequency (19%), the impact of atrial fibrillation (16%) and hypertension (14%) on QoL, PFS (7%), and formulation type (0.6%). Results from the subgroup analyses were generally consistent with the full sample analysis, with impacts of AEs on QoL being the most important factors for treatment decision-making, especially among older patients, although the relative ranking of impacts of AEs varied by age groups and treatment experience. Regarding efficacy, younger patients (<60 years of age) valued PFS slightly more than older patients (≥60 years of age), ranking it 4th and 6th out of the 10 attributes, respectively. Additionally, preference on dosing frequency was more important for 2L+ patients, reflecting the treatment burden experienced from previous regimens. Conclusions: This study provides valuable insights into the treatment preferences of Korean patients with CLL, highlighting the importance of QoL considerations for treatment decision-making. Among the evaluated attributes, patients placed the greatest weight on minimizing the impacts of AEs, particularly headache and diarrhea, on daily functioning, followed by dosing frequency. These preferences underscore the need for patient-centered care that prioritizes not only clinical efficacy but also tolerability and convenience. These insights can inform shared decision-making and support the development of personalized treatment strategies that better align with patient needs and expectations in Korea.

Abstract Anaplastic large cell lymphomas (ALCLs) are CD30+ T-cell lymphomas that share pathologic features but differ in presentation, outcome, and genetics. Current classification incorporates clinical presentation and anaplastic lymphoma kinase (ALK) status but inadequately addresses molecular heterogeneity and therapeutic vulnerabilities. We studied 689 patients with ALCL in the LLMPP (Lymphoma/Leukemia Molecular Profiling Project) and performed expert consensus review, genetic subtyping (ALK, DUSP22, TP63, and triple negative), and immunohistochemistry for phosphorylated STAT3Tyr705. RNA sequencing with unsupervised gene expression profiling in 393 patients identified 2 main molecular types of ALCL that could be predicted with 91% accuracy based on the presence (type I) or absence (type II) of phosphorylated STAT3Y705 expression. Type I ALCLs included ALK+ ALCL and a subset of triple-negative ALCLs (TN-I); type II ALCLs included tumors with DUSP22 and/or TP63 rearrangements and the remaining triple-negative ALCLs (TN-II). Type I ALCLs were enriched for JAK-STAT3, whereas type II ALCLs were enriched for non–tyrosine kinase pathways, particularly epigenetic regulators such as EZH2. Immunohistochemistry showed overexpression of EZH2 and its trimethylated substrate H3K27. Prognosis in systemic ALCL was favorable for DUSP22-rearranged ALCL (5-year overall survival, 95%) and ALK+ ALCL (88%), intermediate for triple-negative ALCL (TN-I, 52% and TN-II, 37%), and poor for TP63-rearranged ALCL (0%). We introduce an integrated molecular classification that preserves currently diagnosed ALCL entities but identifies 4 molecularly distinct ALK− ALCL subtypes (DUSP22-rearranged, TP63-rearranged, TN-I, and TN-II). This classification can be easily implemented on paraffin tissue in routine practice or clinical trials, and stratifies ALCL into diagnostically, prognostically, biologically, and potentially therapeutically relevant subtypes.

Abstract Description The two key determinants of successful vaccines are the ability to induce a protective immune response and a long-lived immune memory. The mechanism determining durability and its contribution to the lower vaccine efficacy in older adults is elusive. We use varicella zoster virus (VZV) vaccination as a model that relies on cellular, not humoral immunity. We compared long-lived antigen-specific memory T cells in adults who were vaccinated at young (<20 years) or older age (>50 years) with a life-attenuated vaccine that confers sustained protection only in young age, or who received an adjuvanted subunit vaccine that is protective at older age. We stimulated PBMCs of vaccine recipients years after vaccination and collected VZV-reactive T cells for spectral flow cytometry and single-cell sequencing. While CD4 T cells were resilient to aging, VZV-specific CD8 T cells lost diversity and lacked stem-like features while gaining end-differentiated, NK-like signatures. These age-associated changes in CD8 T cells were not reversed with the effective subunit vaccine. Instead, this vaccine induced pro-inflammatory VZV-specific TH17 cells. TH17 cells in the less efficient vaccine response, albeit present, were skewed towards a FOXP3+ regulatory phenotype and deficient in TH1 polyfunctionality – a phenotypic shift that is in part controlled by lipid metabolic pathways. Our study uncovers traits of T cell dysfunction with age and informs vaccination efforts tailored towards healthy aging. Funding Sources NIH U19AI057266, R01AG045779, R01AI108891, R01AI129191, T32AG049672, Glenn Foundation for Medical Research Postdoctoral Fellowship, Robert and Arlene Kogod Center on Aging Career Development Award. Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)

Abstract Background The RefleXion X1 is a novel PET/CT‐guided ring gantry linac that introduces unique geometry and workflow compared to conventional systems. Existing QA guidelines (AAPM TG‐142, 148, 306) cover standard linacs and tomotherapy but do not address this platform's needs. Therefore, an automated daily QA solution is required to ensure accurate output, imaging guidance, and couch positioning, which motivated the development and evaluation of the workflow presented in this study. Purpose To develop and evaluate an automated, efficient, and comprehensive daily quality assurance (QA) workflow for a novel PET/CT‐guided ring gantry linear accelerator (RefleXion X1), incorporating tests for dosimetry, imaging guidance, and couch positioning accuracy. Methods An IMRT QA plan was designed following the CT scan of the TomoDose 2D diode detector array (Sun Nuclear, Melbourne, FL) within the RefleXion treatment planning system (TPS). Several spherical targets of varying sizes were contoured to conform the dose distribution to these targets and evaluate beam output, laser localization, profile constancy, and CT‐MV isocenter coincidence. Linear models correlating spatial location of dose peak with intentional shifts in different directions were developed and integrated into an in‐house analysis software, iQA, written in C#. The software was validated for robustness and successfully implemented in clinical practice. Results Validation with 42 intentional shifts showed submillimeter accuracy, with mean deviations of 0.2 mm (X), 0.1 mm (Y), and 0.79 mm (Z), and R 2 values ≥ 0.98. Over 1 year, daily QA data showed stable output constancy (1.006 ± 0.016), left/right target dose constancy (1.007 ± 0.005 and 0.996 ± 0.004), and consistent CT‐MV isocenter offsets (–0.335 ± 0.23 mm in X, 0.19 ± 0.19 mm in Y, and –0.544 ± 0.36 mm in Z). The software also detected a gradual output drift in between, prompting a timely linac adjustment. Conclusion This fully automated, single‐delivery QA workflow enables efficient and robust evaluation of multiple IGRT performance parameters. It improves standardization, reduces human error, and reliably monitors long‐term machine stability. The tools and methodology may be adopted by other clinics seeking a practical and automated daily QA solution. Future developments will focus on incorporating PET QA and rotational couch validations to further enhance the system's comprehensiveness and adaptability.

Abstract Introduction/Objective Plasmablastic lymphoma (PBL) is a rare type of B-cell lymphoma with poor prognosis. They can arise de novo in immune deficiency/dysregulation, associated with transplant or transformation of low grade lymphoma. PBL has been reported with anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. Methods/Case Report 69-year-old male with CLL/SLL, treated with multiple chemotherapy regimens and was in remission. He developed generalized weaknesses. Radiology showed lymphadenopathy. Pathology was positive for DLBCL without MYC and BCL2 rearrangement. Flow cytometry revealed 1% CD5 and CD23 positive. TP53 is negative and mutated IGHV. The PD-1 was negative, favored de novo DLBCL. PET-CT and biopsy confirmed residual disease. For refractory DLBCL, CAR-T cell therapy was initiated. Patient developed PBL diffusely positive for CD138, MUM1, c-MYC and kappa; negative for CD19, CD20, PAX5, CD10, BCL6 and CD79a. MIB-1 was 90%. EBV and HHV8 were negative. BCMA was >95 %, Teclistamab was initiated. The renal function deteriorated and proceeded with palliative care. Results NA Conclusion The nature of Richter transformation or de novo DLBCL into PBL in the setting of immunomodulation with CAR-T is rare occurrence. Molecular and clonality studies are needed to evaluate the pathways of losing B-cell markers to evade lineage specific therapy.

BACKGROUND: Obstructive sleep apnea (OSA) is a prevalent comorbidity strongly associated with cardiovascular diseases, particularly in patients with aortic dissection (AD). However, the long-term impact of severe OSA on survival and distal aortic remodeling after total arch replacement for acute type A aortic dissection (ATAAD) remains unclear. OBJECTIVES: This study aimed to elucidate the specific long-term prognostic impact of severe OSA in patients undergoing ATAAD repair. METHODS: A total of 86 prospectively collected patients who underwent acute type A aortic dissection repair at Beijing Anzhen Hospital between January 2018 and December 2018 were enrolled in the study. All these patients underwent total aortic arch replacement. All patients underwent sleep monitoring within 90 days postoperatively. The association between severe OSA and major adverse events (MAEs) was analyzed using a multivariable Cox proportional hazards model. Kaplan-Meier survival analysis was performed to assess long-term survival. RESULTS: Of these 86 patients, 22 (25.6%) exhibiting severe OSA and 64 (74.4%) not. Individuals with severe OSA had a notably higher rate of major adverse events (MAEs) compared to those without severe OSA (27.3% vs. 7.8%, P =0.047) and a significantly lower long-term survival rate (81.8% vs. 97.4%, P =0.003). After adjusting for potential confounding variables, severe OSA remained an independent predictor of MAEs (HR=3.7, 95% CI: 1.1–12.4, P =0.032). Imaging follow-ups indicated that patients with severe OSA experienced significantly higher stent-graft distal aortic expansion rates (1.8 mm/year vs. 0.4 mm/year, P =0.030), abdominal aortic expansion rates (2.2 mm/year vs. 0.7 mm/year, P <0.001), and false lumen expansion rates in the descending aorta (2.5 mm/year vs. 0.8 mm/year, P =0.003). Moreover, partial thrombosis of the false lumen was more frequently observed in patients with severe OSA (40.9% vs. 14.1%, P =0.028). Conversely, complete false lumen thrombosis (64.1% vs. 45.5%, P =0.028) and false lumen patency (21.9% vs. 13.6%, P =0.028) were more commonly observed in patients without severe OSA. CONCLUSIONS: Severe OSA is associated with an elevated risk of MAEs and is implicated in abnormal distal aortic expansion and false lumen thrombosis among patients undergoing ATAAD repair. These results highlight the importance role of identifying and managing severe OSA in the long-term postoperative care of patients with ATAAD.

Abstract This article provides an overview of deep-learning–based techniques in CT image reconstruction and processing (referred to as “DLR”), covering technical implementations, performance evaluation, radiation dose reduction, and future perspectives. DLR methods can be categorized into projection-space, projection-to-image-space, image-space, and various hybrid techniques, with applications such as noise reduction, artefact correction, and spatial resolution enhancement. Performance evaluations include phantom-based studies, patient image-based studies, and virtual imaging trials. These evaluation studies demonstrated that DLR can effectively reduce image noise while preserving an image texture like in traditional filtered-backprojection (FBP) images, although the extent of radiation dose reduction varies widely depending on the study and the specific diagnostic task. Challenges remain in low-contrast lesion detection and characterization, where dose reduction may still be less than 50% compared to traditional reconstruction methods. Additionally, the potential for DLR methods to generate false structures or “hallucinations,” especially at low radiation doses, emphasizes the need for effective monitoring and mitigation strategies from both technical and clinical perspectives. Quantitative, accurate, and efficient evaluation techniques, such as virtual image trial-based methods, can be explored to help optimize these algorithms for reducing radiation dose and enhancing diagnostic performance.