Grewal, Eric P

ABSTRACT A major challenge in hematopoietic progenitor cell apheresis is determining the whole blood (WB) volume to process to achieve a CD34+ cell collection goal. We developed a web‐based calculator app that uses the Collection Efficiency 2 (CE2) model to estimate personalized WB processing volumes needed to reach a prescribed CD34+ cell collection goal. Retrospective evaluation of the app using collection data from two academic medical centers showed that actual processed WB volumes were frequently higher than the app's recommendations. The frequency of potential under‐collection events is predicted to be low had the app‐calculated volumes been utilized. Our findings suggest that using the app's recommendations may lower total WB processing volumes, reducing over‐collection and time spent on the apheresis machine, while maintaining a low under‐collection risk profile.

Background Neoadjuvant treatment has become standard for patients with high-risk operable stage III melanoma, but the optimal regimen is unknown. Targeted therapy approaches yield high pathological response rates, while immunotherapy regimens show favorable recurrence-free survival (RFS). NeoACTIVATE was designed to address whether a neoadjuvant combination of both targeted therapy and immunotherapy might leverage the benefits of each. Methods We tested neoadjuvant treatment with 12 weeks of vemurafenib, cobimetinib, and atezolizumab for patients with BRAF-mutated (BRAFm) melanoma (cohort A) and cobimetinib and atezolizumab for patients with BRAF-wild-type (BRAFwt) melanoma (cohort B), regimens which we have shown generate a substantial major pathological response. After therapeutic lymph node dissection, patients received 24 weeks of adjuvant atezolizumab. Here, we report survival outcomes and their association with biomarkers assayed among the gut microbiome and peripheral blood immune subsets. Results With 49 months median follow-up, the median RFS was not reached for cohort A and was 40.8 months for cohort B. At 24 months after operation, 2 of 14 cohort A patients and 4 of 13 cohort B patients had experienced distant relapse. Key findings from correlative analyses included diversity, taxonomic and functional metagenomic gut microbiome signals associated with distant metastasis-free survival at 2 years. Notably, we observed a strong correlation between low microbial arginine biosynthesis (required for T-cell activation and effector function) and early distant recurrence (p=0.0005), which correlated with taxonomic differential abundance findings. Peripheral blood immune monitoring revealed increased double-positive (CD4+CD8+) T cells in patients with early recurrence. Conclusions Neoadjuvant treatment with cobimetinib and atezolizumab±vemurafenib was associated with a low rate of distant metastasis in patients with high-risk stage III melanoma. Freedom from early distant metastasis was highly associated with taxonomic differences in gut microbiome structure and with functional pathway alterations known to modulate T cell immunity. Identification of predictive biomarkers will permit optimization of neoadjuvant therapy regimens for individual patients. Trial registration number NCT03554083.

Background Schistosomiasis is a parasitic disease that affects the health of hundreds of millions of people worldwide. Affordable diagnostic methods are necessary for developing countries to monitor schistosomiasis rates and treat infected individuals, particularly in, Madagascar, a country with the world’s fifth highest rate of schistosomiasis. Methods We established the prevalence rate of schistosomiasis among the local population served by a clinic in rural northwestern Madagascar. Additionally, we compared different low-cost methods for schistosomiasis detection, including empirical diagnostic methods in use before this study. 500 patients were recruited in this study, of whom 380 received three tests—urine microscopy, point-of-care circulating cathodic antigen (POC-CCA) testing, and urinalysis to screen for Schistosoma haematobium and Schistosoma mansoni. Results By combining these modalities, we recorded a schistosomiasis prevalence rate of 64.47%, which was significantly higher than the 4.84% of patients who were diagnosed and treated through previous empirical methods. Conclusions Our results indicate that screening tests are a necessary component of schistosomiasis control programs. The clinic continued to use urinalysis strip testing and urine microscopy to detect schistosomiasis after this study and decided to discontinue the use of POC-CCA S. mansoni urine testing because of cost. Increased awareness of schistosomiasis resulting from this screening program led to the installation of multiple infrastructure projects in local communities to improve access to potable water, demonstrating community benefits of schistosomiasis screening that extend beyond the identification of infected individuals.