Risk of repeated febrile episodes during chemotherapy-induced granulocytopenia in children with cancer: a prospective single center study

Abstract

Background: Febrile neutropenia (FN) is a possible complication of antineoplastic chemotherapy. Aim of the study was to estimate the risk of developing fever at the beginning of any neutropenic period based on the previous history of FN.

Procedure: The conditional frailty model was used to estimate the risk of developing fever during neutropenia separately for children with acute leukaemia/non-Hodgkin lymphoma (AL/NHL), or solid tumour (ST). The total number of previous FN episodes (PFNE), age, gender, type of tumour, calendar year of granulocytopenic period, phase of treatment, and granulocyte count were included in the model.

Results: A total of 901 granulocytopenic periods was observed in 223 children: 306 in 66 AL/NHL and 595 in 157 ST. Fever developed in 328 cases: 125 in 53 AL/NHL and 203 in 92 ST. The PFNE variable was not significantly associated to the risk of fever [hazard ratio (HR) of 0·87, 95% confidence interval (CI) of 0·62–1·22 in children with AL/NHL, and HR of 0·98, 95% CI of 0·70–1·37 in those with ST]. The hazard of FN was significantly affected by the phase of treatment in AL/NHL (P<0·01), and by the level of neutropenia at onset in ST (P<0·01).

Conclusions: Previous history of FN does not increase the risk of further febrile episodes in any new subsequent granulocytopenic period. The aggressiveness of chemotherapy and the level of neutropenia at onset are the most important risk factors in children with AL/NHL and with ST respectively.

Keywords:

• Repeated febrile neutropenia
• Discontinuous interval of risk
• Event dependence
• Heterogeneity
• Pediatric cancer
• Epidemiology

The study was partially supported by grants from ‘G. Gaslini’ Children’s Hospital, Italian Foundation for Research on Neuroblastoma and by the European Network for Cancer Research in Children and Adolescents (ENCCA).