By Laura Cowen, medwireNews Reporter
medwireNews: Severe sepsis during treatment for childhood leukaemia may be associated with an increased risk of moderate-to-severe neurocognitive dysfunction in adulthood, US Study findings indicate.
“Prevention of severe sepsis during therapy, as well as recognition and amelioration of neurocognitive deficits through early intervention, might improve quality of life in children who survive childhood cancer”, write Joshua Wolf (St Jude Children’s Research Hospital, Memphis, Tennessee) and co-authors in JAMA Network Open.
They explain that long-term survival rates now exceed 90% for children diagnosed with acute lymphoblastic leukaemia (ALL) and 70% for those with acute myeloid leukaemia (AML), but sepsis is still a risk, and threat to survival, during leukaemia therapy.
Furthermore, there is increasing evidence about the long-term end-organ and psychosocial effects of sepsis, but there are currently no specific guidelines for the follow-up or treatment of survivors of paediatric severe sepsis, the researchers note.
Their study included 644 adult survivors of paediatric leukaemia (51.0% women, median age 24.7 years) without relapse or progression to haematopoietic stem cell transplant who were most recently evaluated at a median 17.3 years after leukaemia diagnosis. Of these, the majority (90.8%) had been diagnosed with ALL, 8.7% had AML and the remaining 0.5% had mixed phenotype acute leukaemia.
Wolf and team report that during leukaemia therapy, 46 (7.1%) participants developed at least one episode of severe sepsis, defined as septic shock, acute respiratory distress syndrome or multiorgan dysfunction associated with infection. Of note, individuals with AML were more likely to develop sepsis than those with ALL, at rates of 28.6% and 5.1%, respectively.
The team found that patients who experienced severe sepsis during treatment had a significantly higher incidence of moderate-to-severe (grade 2 or 3 on the Common Terminology Criteria for Adverse Events) neurocognitive impairment than those with no sepsis, at 63.0% versus 51.8%. This corresponded to a significant 1.86-fold increased risk after adjustment for potential confounders, including age, year of diagnosis and leukaemia type.
Specifically, individuals with a history of sepsis were at significantly higher risk of moderate-to-severe impairment on a battery of neurocognitive tests for attention (adjusted hazard ratio [aHR]=2.37), memory (aHR=2.72), executive function (aHR=2.28) and visuospatial function (aHR=1.86).
The researchers point out that there was no difference between the two groups in the incidence of neurological conditions such as cerebrovascular accidents or seizures, which suggests that these events are not driving the increased rates of neurocognitive dysfunction in the people with sepsis.
“This finding is important because neurocognitive function is a priority for patients, caregivers, and clinicians, and neurocognitive dysfunction in survivors of childhood cancer is associated with significant reductions in rates of college graduation, employment, and income”, they write.
Contrary to their original hypothesis, Wolf et al found that chronic conditions in other organ systems were not significantly associated with sepsis, with no increase in risk of chronic cardiac, pulmonary, kidney or neurological problems.
The investigators say that, at present, the mechanism for the association between sepsis and neurocognitive dysfunction is unknown. “[S]epsis-related encephalopathy can lead to permanent neurocognitive dysfunction and functional impairments and may increase the risk of vascular and psychiatric disease, but this exposure was rare in our cohort and did not seem to explain the identified neurocognitive defects.”
They suggest: “An alternative explanation is that cerebral damage might be potentiated in children with severe sepsis by increased exposure to neurotoxic chemotherapy drugs during periods of sepsis-induced increases in blood-brain barrier permeability.”
The authors conclude that “more research is needed to validate these findings, identify potential mechanisms, and develop ameliorative interventions.”
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JAMA Netw Open 2024; 7: e242727