By Benjamin Ross
March 7, 2019 | Chemotherapy for children with acute lymphoblastic leukemia (ALL) can put them at risk for infection, often with morbid results. Researchers at St. Jude Children’s Research Hospital have analyzed the role of the gut microbiome in predicting whether children might develop infections prior to, during, and after chemotherapy. The results were published in Clinical Infectious Diseases (DOI: https://doi.org/10.1093/cid/ciy153).
Jason Rosch, an associate member of St. Jude in the infectious disease department and one of the lead investigators of the study, told Diagnostics World the goal of the study was to see if microbiome sampling from patients could be used as a measure to predict infection risk.
“Patients undergoing chemotherapy tend to be very, very immuno-suppressed, and they tend to be susceptible to infections,” Rosch said. “So coming up with ways to potentially predict which are the most high risk patients for infections would be an invaluable tool for us.”
The underlying question researchers were attempting to answer was whether or not the knowledge known about the microbiome in adults could be applied to children as well, Rosch said.
“Years ago there was an increase in evidence, especially in adult patients, that you could use the microbiome to predict infection risk,” said Rosch. “However, nobody ever tried doing this with pediatrics until we decided to give it a try.”
Rosch and his team found that the diversity of the children’s microbiomes decreased from initial diagnosis after the end of the chemotherapy process, while diversity reverted to baseline with less-intensive treatment.
The sheer amount of data the researchers were handling was a challenge, Rosch said.
“These are really complex data sets because you have a [microbe] community structure analysis, but there are a lot of things that go into infection risk prediction,” he said. “There are a lot of variables to consider in the analysis, so it was a big task for our biostatisticians.”
Researchers collected fecal samples from 199 patients at diagnosis and at each of the three initial stages of the chemotherapy process. The samples were then analyzed using high-depth sequencing on Illumina’s Mi-seq platform. Specifically, researchers focused on the bacterial 16s rRNA gene in order to determine the composition of the children’s microbiomes.
In analyzing the samples, researchers concluded that, “the composition, rather than diversity, of baseline gut microbiome was an independent predictor of [fever] during chemotherapy,” according to the study’s authors. They also determined that patients with a deficiency of Proteobacteria at the point of leukemia diagnosis had a 67% of developing fever.
Now, St. Jude is working on a follow up study, asking if the results from this study can be refined.
“We’re working with an extended patient base to ask the questions: Can this be applied with more frequent sampling? Can we refine our models? Can we validate this data set?” Rosch said. “We’ve got plenty of data to work with for the next couple of years.”
The hope for Rosch and other researchers at St. Jude is that these results will provide insight into risk assessment for children diagnosed with leukemia and provide clinicians with the best information when choosing treatment options.
“It really is a complex, multi-faceted challenge for patients,” said Rosch. “I think it really takes a whole community from infection control to all the doctors that are involved in patient care to really improve these outcomes.”