Factors influencing predisposition to sepsis in children with cancers and acquired immunodeficiencies unrelated to human immunodeficiency virus infection

Abstract

Objectives: The main objectives of this review are to provide insight into the various factors that affect the risk of sepsis in immunocompromised children and to discuss special issues that should be considered when such patients are enrolled in clinical trials.

Strategy: A literature review was conducted, and authoritative references were consulted when appropriate. This was supported by discussion among experts at an international consensus conference on pediatric sepsis.

Outcome: The review discusses general issues as they relate to the factors that are associated with a predisposition to sepsis in children with cancers and non-human immunodeficiency virus (HIV)-related acquired immunodeficiencies. The host defects that are associated with specific infections are discussed, and an overview of the indicators of immune dysfunction in the previously well child is presented. Selected examples of patients with non-HIV-related acquired immunodeficiencies, including those with cancer or who have undergone solid-organ or hematopoietic stem-cell transplants are discussed. Special challenges that may affect clinical trials include the altered immune response as this relates to the definition of infection and disease and the assessment of outcomes and the heterogeneity of study populations due to the variable manifestations of immune deficiency states.

Summary: Knowledge of the factors that are associated with sepsis in immunocompromised patients is important when such patients are to be entered into clinical trials on sepsis. These factors do not necessarily operate in isolation and may occur concurrently or sequentially. With these considerations in mind, clinical trials involving immunocompromised children can go forward and will very likely lead to significant advances in the care of this understudied population.