Gut microbiome changes in pediatric AML and association with event free survival.

Abstract

10026 Background: Pediatric acute myeloid leukemia (AML) is characterized by months of hospitalization with a high risk for infections and a higher rate of relapse than many pediatric leukemias. Recent studies have highlighted the relationship between gut microbiome changes, long term cancer outcomes, and development of comorbidities. However, no study to date has examined the longitudinal changes in the gut microbiome in pediatric AML patients. Methods: In this retrospective study, longitudinal stool samples were taken from 14 pediatric patients with AML treated at Children’s Hospital Colorado. Sample collection started after initial diagnosis for 11 patients and after first relapse for 3 patients. These samples were analyzed using 16S ribosomal RNA (rRNA) gene sequencing along with clinical data extracted via manual chart review. Results: We found that the relative abundance of genus Fusobacterium was associated with relapses. Analysis indicated that Fusobacterium was significantly elevated in the stool of 3 of 6 newly diagnosed patients who relapsed within 5 years (using a linear model that also accounted for risk stratification based on genetics and treatment response (p = 0.03)). These patients had elevated Fusobacterium at multiple timepoints during treatment. Samples from the 5 newly diagnosed patients who did not relapse showed minimal Fusobacterium . Fusobacterium has previously been associated with other cancers, oncogenesis and immune evasion. Of the 14 patients, 5 experienced 1-4 cases of Streptococcus mitis bacteremia (SMB) during the sample collection period. Genus Streptococcus abundance in stool samples collected immediately prior to SMB did not correlate with positive blood cultures, although this genus was highly prevalent in the gut microbiome of patients with repeated episodes. Using mixed effects random forest model (MERFM) to broadly survey whether changes in any other gut bacteria predicted a positive SM blood culture, we found evidence for a negative relationship between SMB and change in relative abundance of genus Blautia , and a positive relationship with the genera Marvinbryantia, Anaerococcus, Parabacteroides and Dielma . This suggests that other aspects of microbiome composition may influence whether Streptococcus can translocate into the bloodstream. Of the 14 patients, 4 developed Clostridioides difficile infections (CDI) during the collection period. Increases in genus Clostridioides relative abundance occurred prior to clinical CDI. Using MERFM, Faith Phylogenetic Diversity was negatively related to development of CDI and presence of the genera Anarofustis, Bilophila, Alistipes and was positively related to CDI. Conclusions: These results show that the gut microbiome may be implicated or serve as a prognostic indicator for relapse in pediatric AML. Additionally, longitudinal gut microbiome changes in patients may be associated with various clinical complications.