Method identified to reduce risk of brain damage in leukemia survivors

St. Jude Children’s Research Hospital scientists report link between sepsis during acute lymphoblastic leukemia treatment and later neurocognitive problems

Memphis, Tennessee, September 24, 2018

Josh Wolf, MBBS

Josh Wolf, MBBS, assistant member of the St. Jude Department of Infectious Diseases

Children with acute lymphoblastic leukemia (ALL) are at an extremely high risk of sepsis compared to the general population. In the first-published study of its kind, St. Jude Children’s Research Hospital scientists have discovered a link between sepsis during cancer treatment and long-term neurocognitive dysfunction.

Sepsis is a potentially life-threatening condition in which the body wages a massive immune response to a bacterial infection of the blood. The study revealed survivors with a history of sepsis performed worse than other participants on tests measuring multiple neurocognitive domains, including executive function and attention span.

“By preventing infection and sepsis, we’re able to help avert long-term problems for survivors,” said Josh Wolf, MBBS, assistant member of the St. Jude Department of Infectious Diseases.

The study, led by Wolf and Kevin Krull, Ph.D., a member of the St. Jude Department of Epidemiology and Cancer Control, appears today in the journal JAMA Pediatrics.

“Cancer patients have a high risk of acquiring infection,” Wolf said. “There’s also a high risk of that infection becoming serious. Then, because their body can’t control the bacteria, they’re susceptible to sepsis.”

Kevin Krull, Ph.D.

Kevin Krull, Ph.D., a member of the St. Jude Department of Epidemiology and Cancer Control

The sepsis then leads to the late effects of neurocognitive dysfunction. Children who had bloodstream infections without sepsis avoided those late effects, although other factors, including ALL treatment, are associated with neurocognitive problems among ALL survivors. The severity of sepsis did not matter.

“The children who had sepsis did worse than the children who did not,” Wolf said. “When we divided the kids who had sepsis into levels ranging from severe sepsis versus not-so-severe sepsis, they looked the same.”

The patients in this study suffered long-term cognitive deficits, whether the instance of sepsis during treatment was mild or severe. This makes it important to identify the infection early and appropriately treat it.

“Aggressive management of infection before it progresses to sepsis is extremely important,” Krull said. “If we know a child who develops sepsis will be at risk for future attention and executive-function problems as a long-term survivor, we can immediately start training these attention and executive function skills. The training can occur after the child recovers from sepsis and is still undergoing cancer therapy. If we strengthen the attention and executive function skills then, perhaps these children will not decline to below-average performance.”

The mechanism behind the long-term cognitive effects of sepsis is not known, but pre-emptive neurocognitive interventions may prevent or mitigate any neurological damage. Wolf and others are conducting research to understand the association between sepsis and neurocognitive problems.

The other authors are Yin Ting Cheung of The Chinese University of Hong Kong; and Aaron Eskind, Hiroto Inaba, Melissa Hudson and Ching-Hon Pui, all of St. Jude.

The research was funded in part by a grant (MH085849) from the National Institute of Mental Health; a grant (ICA195557) from the National Cancer Institute; and ALSAC, the fundraising and awareness organization of St. Jude.

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20 percent to 80 percent since the hospital opened more than 50 years ago. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. Families never receive a bill from St. Jude for treatment, travel, housing and food — because all a family should worry about is helping their child live. To learn more, visit stjude.org or follow St. Jude on social media at @stjuderesearch.