Baseline body mass index among children and adults undergoing allogeneic hematopoietic cell transplantation: clinical characteristics and outcomes

Obesity is an important public health problem that may influence the outcomes of hematopoietic cell transplantation (HCT). We studied 898 children and adults receiving first-time allogeneic hematopoietic stem cell transplants between 2004 and 2012. Pre-transplant body mass index (BMI) was classified as underweight, normal weight, overweight, or obese using the WHO classification, or age-adjusted BMI percentiles for children. The study population was predominantly Caucasian, and the median age was 51 years (5 months – 73 years). The cumulative 3-year incidence of non-relapse mortality (NRM) in underweight, normal weight, overweight, and obese patients was 20%, 19%, 20%, and 33%, respectively. Major causes of NRM were acute and chronic graft-versus-host disease (GVHD). The corresponding incidence of relapse was 30%, 41%, 37%, and 30%, respectively. Three-year overall survival was 59%, 48%, 47%, and 43%, respectively. Multivariate analysis showed that obesity was associated with higher NRM (HR 1.43, p=0.04), and lower relapse (HR 0.65, p=0.002). Pre-transplant plasma levels of ST2 and TNFR1 biomarkers were significantly higher in obese compared with normal weight patients (p=0.04 and p=0.05, respectively). The increase in NRM observed in obese patients was partially offset by lower incidence of relapse with no difference in overall survival

Terminally exhausted CD8+ T cells contribute to age-dependent severity of respiratory virus infection

Abstract Background Lower respiratory infections are a leading cause of severe morbidity and mortality among older adults. Despite ubiquitous exposure to common respiratory pathogens throughout life and near universal seropositivity, antibodies fail to effectively protect the elderly. Therefore, we hypothesized that severe respiratory illness in the elderly is due to deficient CD8+ T cell responses. Results Here, we establish an aged mouse model of human metapneumovirus infection (HMPV) wherein aged C57BL/6 mice exhibit worsened weight loss, clinical disease, lung pathology and delayed viral clearance compared to young adult mice. Aged mice generate fewer lung-infiltrating HMPV epitope-specific CD8+ T cells. Those that do expand demonstrate higher expression of PD-1 and other inhibitory receptors and are functionally impaired. Transplant of aged T cells into young mice and vice versa, as well as adoptive transfer of young versus aged CD8+ T cells into Rag1 −/− recipients, recapitulates the HMPV aged phenotype, suggesting a cell-intrinsic age-associated defect. HMPV-specific aged CD8+ T cells exhibit a terminally exhausted TCF1/7− TOX+ EOMES+ phenotype. We confirmed similar terminal exhaustion of aged CD8+ T cells during influenza viral infection. Conclusions This study identifies terminal CD8+ T cell exhaustion as a mechanism of severe disease from respiratory viral infections in the elderly