"CLO25-066: Prognostic Role of Pre-Transplant EASIX on Non-Relapse Mortality and Overall Survival in Allogeneic Stem Cell Transplantation: A Meta-Analysis" published on 28 Mar 2025 by National Comprehensive Cancer Network.

From the 2026 National Summit on Hematologic Cancers

Purpose: Obesity is a risk factor for sepsis complications in older adults. We assessed the impact of metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO) on outcomes in septic shock. Methods: We conducted a retrospective analysis using the National Inpatient Sample (2016-2020) to identify a cohort of 1,737,075 patients aged 65 years and older who were hospitalized with septic shock, as defined by ICD-10 diagnosis codes. Obese patients without hypertension, diabetes, or hyperlipidemia were classified as MHO; those with ≥1 risk factor as MUHO. Baseline demographics and hospital characteristics were compared using χ² and Mann–Whitney U tests. Multivariable logistic regression adjusted for age, sex, race, comorbidity index, and hospital factors estimated odds ratios (ORs) for respiratory failure, mechanical ventilation, in-hospital mortality, and cardiac arrest. Secondary endpoints included length of stay (LOS) and hospitalization cost. Results: Among 268 050 obese patients, 23 915 (1.4%) were classified as MHO and 244 135 (14.1%) as MUHO. Both phenotypes were more prevalent in females and least common among Asian patients. MHO prevalence was highest among Native Americans, while MUHO was most common among Hispanics in 2020. From 2016 to 2019, the prevalence of both phenotypes remained stable, with modest increases observed during the 2020 sepsis surge. Respiratory failure occurred most frequently in the MHO group (∼70%), followed by MUHO (∼65%) and non-obese patients (∼60%). After adjusting for confounders, both MHO and MUHO groups had higher odds of respiratory failure and mechanical ventilation compared to non-obese patients. In-hospital mortality increased across all groups in 2020; however, MUHO patients had lower adjusted mortality risk. Cardiac arrest rates remained unchanged, while length of stay and hospitalization costs were highest among MHO patients. Conclusions: MHO and MUHO both confer higher respiratory failure and ventilation risk; lower mortality in MUHO warrants further study. Clinical Implications: Phenotypic obesity classification may improve sepsis risk stratification and inform metabolic-specific management.

Patients with multiple myeloma (MM) exhibit profound immune dysregulation, predisposing them to severe outcomes following SARS-CoV-2 infection. Current evidence highlights shared immunopathological mechanisms linking MM and COVID-19, with particular emphasis on the interleukin-6 (IL-6) axis as a shared amplifier of inflammation rather than the sole driver of disease. MM is characterized by a baseline pro-inflammatory milieu, in part mediated by IL-6, which is further amplified during SARS-CoV-2 infection, resulting in cytokine escalation, complement activation, coagulopathy, and multi-organ injury. This amplification operates within a broader, redundant network that also includes T-cell exhaustion, NK-cell dysfunction, checkpoint signaling, complement and endothelial injury, and treatment-induced immune defects. This overlap provides a mechanistic basis for the disproportionately high morbidity and mortality observed in this population. Even with advancements in vaccination, antiviral therapy, and clinical practice, patients with MM who exhibit impaired vaccine responses, active disease, or treatment-related immune dysfunction continue to experience considerable vulnerability to COVID-19. In addition, MM patients demonstrate suboptimal vaccine-induced immune responses, contributing to persistent vulnerability to severe and breakthrough infections. Modern MM therapies, including anti-CD38 antibodies, BCMA-directed agents, and bispecific T-cell redirecting antibodies, further reshape antiviral immunity by reducing NK cells, inducing plasma cell aplasia, causing hypogammaglobulinemia, and impairing T-cell function. Emerging treatment approaches targeting this shared pathway have been explored, with a focus on mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs). EVs exhibit multimodal properties, including suppression of pro-inflammatory cytokines, restoration of immune homeostasis, inhibition of viral entry, and promotion of tissue repair and regeneration. Early clinical experience in severe COVID-19 populations suggests a favorable short-term safety profile; reported efficacy, however, derives from small, largely uncontrolled or early-phase studies, and the single randomized trial reporting a mortality benefit did so only in an exploratory post hoc subgroup, with its pre-specified primary endpoint not met. Overall, EVs constitute a biologically plausible but as yet unproven adjunctive strategy that warrants further investigation. Critically, no MM patient has ever been enrolled in an EV trial; current rationale for EV use in MM is therefore extrapolated entirely from non-MM populations, and no MM-specific data exist. Difficulties such as EV heterogeneity, manufacturing variability, uncertain pharmacokinetics, limited targeting efficiency, and potential prothrombotic effects must be resolved before their application in MM-specific clinical settings.

From the 2026 National Summit on Hematologic Cancers