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Introduction: In order to study the role of the microbiome in hematopoietic stem cell transplantation (HCT), researchers collect stool samples from patients at various time points throughout HCT. However, stool collection requires active subject participation and may be limited by patient reluctance to handling stool. Methods: We performed a prospective study on the impact of financial incentives on stool collection rates. The intervention group consisted of allogeneic HCT patients from 05/2017-05/2018 who were compensated with a $10 gas gift card for each stool sample. The intervention group was compared to a historical control group of allogeneic HCT patients from 11/2016-05/2017 who provided stool samples before the incentive was implemented. To control for possible changes in collections over time, we also compared a contemporaneous control group of autologous HCT patients from 05/2017-05/2018 with a historical control group of autologous HCT patients from 11/2016-05/2017; neither autologous HCT group was compensated. The collection rate was defined as the number of samples provided divided by the number of time points we attempted to obtain stool. Results: There were 35 allogeneic HCT patients in the intervention group, 19 allogeneic HCT patients in the historical control group, 142 autologous HCT patients in the contemporaneous control group (that did not receive a financial incentive), and 75 autologous HCT patients in the historical control group. Allogeneic HCT patients in the intervention group had significantly higher average overall collection rates when compared to the historical control group allogeneic HCT patients (80% vs 37%, p<0.0001). There were no significant differences in overall average collection rates between the autologous HCT patients in the contemporaneous control and historical control groups (36% vs 32%, p = 0.2760). Conclusion: Our results demonstrate that a modest incentive can significantly increase collection rates. These results may help to inform the design of future studies involving stool collection. [ABSTRACT FROM AUTHOR]

Allogeneic-HCT (allo-HCT), while potentially curative, can result in significant complications including graft versus host disease (GVHD). Prior studies suggest that metabolic syndrome may be one risk factor for GVHD. We hypothesized that hepatic steatosis on pre-HCT computed tomography (CT) scans may be a marker for development of GVHD and poor outcomes in allo-HCT. In this retrospective study, we reviewed the pre-HCT CT scans and transplant outcome data of patients who underwent allo-HCT at Duke University Medical Center from 2009 to 2017. The presence of steatosis was confirmed using CT attenuation measurements. We then assessed the association between pre-HCT hepatic steatosis and HCT-related outcomes including GVHD. 80 patients who had pre-HCT CT scans were included in the study. Pre-transplant hepatic steatosis was associated with the development of chronic GVHD (OR 4.2, p = 0.02), but was not associated with acute GVHD (OR 1.3, p = 0.7), non-relapse mortality (p = 0.81) or overall survival (p = 0.74). Based on this single center retrospective study, pre-transplant hepatic steatosis is associated with development of chronic GVHD. Further, prospective study with other imaging modalities including non-contrasted CT scans is needed to determine if this association is reproducible. [ABSTRACT FROM AUTHOR]

Measurable residual disease (MRD) testing after initial chemotherapy treatment can predict relapse and survival in acute myeloid leukemia (AML). However, it has not been established if repeat molecular or genetic testing during chemotherapy can offer information regarding the chemotherapy sensitivity of the leukemic clone. Blood from 45 adult AML patients at day 1 and 4 of induction (n = 35) or salvage (n = 10) cytotoxic chemotherapy was collected for both quantitative real-time PCR (qPCR) assessment (WT1) and next generation sequencing (>500 × depth) of 49 gene regions recurrently mutated in MDS/AML. The median age of subjects was 62 (23–78); 42% achieved a complete response. WT1 was overexpressed in most patients tested but was uninformative for very early MRD assessment. A median of 4 non-synonymous variants (range 0–7) were detected by DNA sequencing of blood on day 1 of therapy [median variant allele frequency (VAF): 29%]. Only two patients had no variants detectable. All mutations remained detectable in blood on day 4 of intensive chemotherapy and remarkably the ratio of mutated to wild-type sequence was often maintained. This phenomenon was not limited to variants in DNMT3A, TET2 , and ASXL1. The kinetics of NPM1 and TP53 variant burden early during chemotherapy appeared to be exceptions and exhibited consistent trends in this cohort. In summary, molecular testing of blood on day 4 of chemotherapy is not predictive of clinical response to cytotoxic induction therapy in AML. The observed stability in variant allele frequency suggests that cytotoxic therapy may have a limited therapeutic index for clones circulating in blood containing these mutations. Further validation is required to confirm the utility of monitoring NPM1 and TP53 kinetics in blood during cytotoxic therapy. [ABSTRACT FROM AUTHOR]

Background: Relationships between microbiota composition and clinical outcomes after allogeneic hematopoietic-cell transplantation have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable., Methods: The microbiota composition of fecal samples obtained from patients who were undergoing allogeneic hematopoietic-cell transplantation at four centers was profiled by means of 16S ribosomal RNA gene sequencing. In an observational study, we examined associations between microbiota diversity and mortality using Cox proportional-hazards analysis. For stratification of the cohorts into higher- and lower-diversity groups, the median diversity value that was observed at the study center in New York was used. In the analysis of independent cohorts, the New York center was cohort 1, and three centers in Germany, Japan, and North Carolina composed cohort 2. Cohort 1 and subgroups within it were analyzed for additional outcomes, including transplantation-related death., Results: We profiled 8767 fecal samples obtained from 1362 patients undergoing allogeneic hematopoietic-cell transplantation at the four centers. We observed patterns of microbiota disruption characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota was associated with a lower risk of death in independent cohorts (cohort 1: 104 deaths among 354 patients in the higher-diversity group vs. 136 deaths among 350 patients in the lower-diversity group; adjusted hazard ratio, 0.71; 95% confidence interval [CI], 0.55 to 0.92; cohort 2: 18 deaths among 87 patients in the higher-diversity group vs. 35 deaths among 92 patients in the lower-diversity group; adjusted hazard ratio, 0.49; 95% CI, 0.27 to 0.90). Subgroup analyses identified an association between lower intestinal diversity and higher risks of transplantation-related death and death attributable to graft-versus-host disease. Baseline samples obtained before transplantation already showed evidence of microbiome disruption, and lower diversity before transplantation was associated with poor survival., Conclusions: Patterns of microbiota disruption during allogeneic hematopoietic-cell transplantation were similar across transplantation centers and geographic locations; patterns were characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota at the time of neutrophil engraftment was associated with lower mortality. (Funded by the National Cancer Institute and others.)., (Copyright © 2020 Massachusetts Medical Society.)