Severe Sepsis During Treatment for Childhood Leukemia and Sequelae Among Adult Survivors
Authors: Goggin Kathryn P. , Lu Lu , Lee Danielle E. , Howell Carrie R. , Srivastava Deokumar , Brinkman Tara M. , Armstrong Gregory T. , Bhakta Nickhill , Robison Leslie L. , Ehrhardt Mathew J. , Hudson Melissa M. , Krull Kevin R. , Pui Ching-Hon , Rubnitz Jeffrey , Ness Kirsten K. , Wolf Joshua 
Published: March 2024

Importance

Children undergoing treatment for leukemia are at increased risk of severe sepsis, a dysregulated immune response to infection leading to acute organ dysfunction. As cancer survivors, they face a high burden of long-term adverse effects. The association between sepsis during anticancer therapy and long-term organ dysfunction in adult survivors of childhood cancer has not been examined.

Objective

To determine whether severe sepsis during therapy for leukemia in childhood is associated with subsequent chronic health conditions in adult survivors.

Design, Setting, and Participants

This cohort study included 644 adult survivors of childhood leukemia who were diagnosed between January 1, 1985, and July 19, 2010, and participated in the St Jude Lifetime Cohort Study. Participants were excluded if they received hematopoietic cell transplant or had relapsed leukemia. Data collection ended June 30, 2017. Data were analyzed from July 1, 2020, to January 5, 2024.

Exposures

Severe sepsis episodes, defined according to consensus criteria as septic shock, acute respiratory distress syndrome, or multiorgan dysfunction associated with infection occurring during anticancer therapy, were abstracted by medical record review for all participants.

Main Outcomes and Measures

Common Terminology Criteria for Adverse Events–defined chronic health condition outcomes were independently abstracted. Associations between sepsis and cumulative incidence of chronic health conditions (eg, cardiovascular, pulmonary, kidney, neurological, and neurocognitive outcomes) were compared by adjusted hazard ratios from Cox proportional hazards logistic regression. Inverse propensity score weighting was used to adjust for potential confounders, including age, year of diagnosis, and leukemia type.

Results

The study sample consisted of 644 adult survivors of pediatric leukemia (329 women [51.1%] and 315 men [48.9%]; including 56 with a history of acute myeloid leukemia and 585 with a history of acute lymphoblastic leukemia) who were most recently evaluated at a median age of 24.7 (IQR, 21.2-28.3) years at a median time after leukemia diagnosis of 17.3 (IQR, 13.7-21.9) years. Severe sepsis during treatment of acute childhood leukemia occurred in 46 participants (7.1%). Participants who experienced severe sepsis during treatment were more likely to develop moderate to severe neurocognitive impairment (29 of 46 [63.0%] vs 310 of 598 [51.8%]; adjusted hazard ratio, 1.86 [95% CI, 1.61-2.16]; P &amp;lt; .001) significantly affecting attention, executive function, memory and visuospatial domains. Sepsis was not associated with long-term risk of cardiovascular, pulmonary, kidney, or neurological chronic health conditions.

Conclusions and Relevance

In this cohort study of long-term outcomes in survivors of pediatric leukemia, severe sepsis during anticancer therapy for leukemia was associated with a selectively increased risk for development of serious neurocognitive sequelae. Efforts to reduce the effects of anticancer therapy on long-term function and quality of life in survivors might include prevention of severe sepsis during therapy and early detection or amelioration of neurocognitive deficits in survivors of sepsis.