No abstract

The number of Tregs, defined as CD4+CD25(hi) T cells is increased in patients with MM and RCC. High-dose IL-2 resulted in a significant decrease of Tregs in those patients achieving an objective clinical response to IL-2 therapy.

The red cell distribution width (RDW) is a component of the automated complete blood count (CBC) that quantifies heterogeneity in the size of circulating erythrocytes. Higher RDW values reflect greater variation in red blood cell (RBC) volumes and are associated with increased risk for cardiovascular disease (CVD) events. The mechanisms underlying this association are unclear, but RBC deformability might play a role. CBCs were assessed in 293 adults who were clinically examined. RBC deformability (expressed as the elongation index) was measured using a micro fluidic slit-flow ektacytometer. Multivariate regression analysis identified a clear threshold effect whereby RDW values above 14.0% were significantly associated with decreased RBC deformability (β = −0.24; p = 0.003). This association was stronger after excluding anemic participants (β = −0.40; p = 0.008). Greater variation in RBC volumes (increased RDW) is associated with decreased RBC deformability, which can impair blood flow through the microcirculation. The resultant hypoxia may help to explain the previously reported increased risk for CVD events associated with elevated RDW.

Aging strongly promotes inflammation responses, which may predispose individuals after cancer therapies to lethal system toxicities and pathology that can be partially prevented by TNF blockade.

Vaccinations are effective in preventing infections; however, it is unknown if patients with chronic lymphocytic leukemia (CLL) who are treatment naïve (TN) or receiving Bruton tyrosine kinase inhibitors (BTKis) respond to novel adjuvanted vaccines. Understanding the effect of BTKis on humoral immunity is timely because BTKis are widely used and vaccination against COVID-19 is urgently needed. In two open-label, single-arm clinical trials, we measured the effect of BTKis on de novo immune response against recombinant hepatitis B vaccine (HepB-CpG) and recall response against recombinant zoster vaccine (RZV) in CLL patients who were TN or on BTKi. The primary endpoint was serologic response to HepB-CpG (anti-HBs ≥10 mIU/mL) and RZV (≥4-fold increase in anti-glycoprotein E). The response rate to HepB-CpG was lower in patients on BTKi (3.8% [95% CI, 0.7%-18.9%]) than TN patients (28.1% [95% CI, 15.6%-45.4%], P=.017). In contrast, the response rate to RZV did not differ significantly between the BTKi (41.5% [95% CI, 27.8%-56.6%]) and TN cohorts (59.1% [95% CI, 38.7%-76.7%], P=.2). BTKis were associated with a decreased de novo immune response following HepB-CpG, whereas recall immune response following RZV was not significantly affected by BTKi therapy. Trials were registered at www.clinicaltrials.gov as NCT03685708 (Hep-CpG) and NCT03702231 (RZV).