Incidence and risk factors of bacterial and fungal infection during induction chemotherapy for high-risk neuroblastoma

Abstract

High-risk neuroblastoma is an aggressive childhood cancer with poor outcomes. Treatment begins with an induction phase comprised of intense multi-agent chemotherapy with the goal of maximally reducing tumor bulk. Given the high intensity of induction chemotherapy, neutropenic fever and infectious complications are common; however, the actual incidence is difficult to determine from clinical trial reports. We performed a retrospective review of infection-related complications in 76 children treated for high-risk neuroblastoma at Texas Children's Hospital. Medical records were reviewed for demographics, febrile neutropenia (FN) episodes, presence, and type of bacterial and fungal infections, and potential risk factors for infection. Fifty-seven percent of patients developed one or more serious bacterial or fungal infections during induction chemotherapy. Additionally, over 75% of patients had at least one admission for FN. Risk factors for developing any infection included female sex, MYCN amplification, and having Medicaid. Patients with external central venous catheters and those requiring parenteral nutrition had higher rates of bacteremia or fungemia. Each cycle, 50% were readmitted for either FN or infection. The overall burden of infectious complications was high, with 70% having two or more unplanned admissions for infection or FN. The incidence of febrile neutropenia and serious bacterial and fungal infections during induction chemotherapy for high-risk neuroblastoma is high. Most patients had at least two additional hospitalizations for infectious complications. Risk factors including female sex, MYCN amplification, payer status, and type of central access were associated with higher rates of infection in this cohort.

Abbreviations: CLABSI Central line associated blood stream infection; CTCAE Common Terminology Criteria for Adverse Events; FN Febrile neutropenia; ANC Absolute neutrophil count; TPN Total parenteral nutrition.

Keywords: Bacterial; chemotherapy; febrile neutropenia; fungal; infection; neuroblastoma.

Figure 1

Percent of subjects with 0, 1, 2 or greater than or equal to 3 bacterial/fungal infections or febrile neutropenia episodes over 5 cycles of induction chemotherapy

Figure 2

Rate of infections or febrile neutropenia following each cycle

Figure 3

A) Distribution of infection types B) Distribution of organisms causing blood stream infections