Genomic Profiling Reveals Differences in Primary Central Nervous System Lymphoma and Large B-Cell Lymphoma, With Subtyping Suggesting Sensitivity to BTK Inhibition.

BACKGROUND: B-cell primary central nervous system (CNS) lymphoma (PCL) is diffuse large B-cell lymphoma (DLBCL) confined to the CNS. Less than 50% of patients with PCL achieve complete remission with current therapies. We describe the findings from comprehensive genomic profiling (CGP) of a cohort of 69 patients with PCL, 36 cases of secondary CNS lymphoma (SCL), and 969 cases of DLBCL to highlight their differences and characterize the PCL cohort. In addition, we highlight the differences in frequency of germinal center B-cell like (GCB) and non-GCB subtypes and molecular subtypes, particularly MCD and EZH subtypes, between PCL and DLBCL. MATERIALS AND METHODS: Sixty-nine cases of B-cell PCL, 36 cases of secondary CNS lymphoma (SCL), and 969 cases of DLBCL were evaluated by CGP of 405 genes via DNAseq and 265 genes via RNAseq for fusions (FoundationOne Heme). Tumor mutational burden (TMB) was calculated from 1.23 Mb of sequenced DNA. RESULTS: Genomic alterations with significant differences between PCL and DLBCL included MYD88, ETV6, PIM1, PRDM1, CXCR4, TP53, and CREBBP, while only MYD88 was significantly different between SCL and DLBCL. PCL cases were significantly enriched for the MCD molecular subtypes, which have an excellent response to BTKi. We report a patient with a durable complete response to BTKi consistent with their genomic profile. EBV status, CD274 amplification, and TMB status suggest that 38% of PCL patients may benefit from ICPI; however further study is warranted. CONCLUSION: CGP of PCLs reveals biomarkers, genomic alterations, and molecular classifications predictive of BTKi efficacy and potential ICPI efficacy. Given the limitations of standard of care for PCL, CGP is critical to identify potential therapeutic approaches for patients in this rare form of lymphoma.

Impact of microbial waste additives and glucose on ammonia emissions from broiler litter in the lab.

Ammonia (NH3) produced inside livestock houses can adversely affect animal welfare and performance and degrade the environment. In broiler houses, NH3 levels are mitigated by applying acidifiers to the litter but acidifiers provide short-term NH3 suppression requiring heavy or repeated applications. Microbial additives may provide longer-term NH3 control through nitrogen (N) immobilization and nitrification. The objective of this 50-d lab study was to evaluate the impact of two microbial additives (Environoc 301 and Environoc 501), 2% glucose, and distilled water (control) treatments applied to broiler litter on NH3 emissions and litter properties. During the first 34 d, glucose significantly but modestly reduced NH3 emissions vs. the other treatments which were not significantly different from one-another. For the entire study, when glucose was excluded (due to lost replicates), the three treatments were not significantly different. The unreplicated glucose treatment had higher final litter nitrate concentration than the other treatments. Litter properties were unaffected by the two microbial additive and control treatments. The effectiveness of glucose in reducing NH3 emission could have been due to greater N immobilization and nitrification vs. the other treatments. More research on cost-effective labile carbon sources and higher application rates to achieve greater NH3 reduction is required.