Delayed Versus Initial Risk-Categorization of Pediatric Cancer Patients with Prolonged Febrile Neutropenia. A Randomized, Prospective Clinical Trial.

Purpose:

Hospitalization with empiric broad spectrum intravenous antibiotics has been the standard of care for treatment of high-risk febrile neutropenia. In an attempt to improved hospital utilization we attempt to identify a group of patients at a lower risk of sepsis that would be eligible for outpatient therapy. We hypothesized that patients initially considered at high risk for sepsis can be candidates for outpatient therapy if at 72 hours satisfied certain selection criteria.

Patients and methods:

A prospective, randomized clinical trial was conducted in 119 febrile neutropenic pediatric cancer patients. Patients were randomized into two groups depending on the time of risk-categorization: Initial (control) vs. delayed (study) groups. Patients in the study group were risk-assessed at 72 hours and accordingly considered for outpatient therapy if afebrile, had an absolute neutrophil count (ANC) > 100/uL, negative blood cultures, and no signs of infection among other carefully defined “Early Discharge Criteria”. Those randomized to the control group were treated in the hospital. We analyzed the clinical features, microbiological data, hospital course, duration of hospitalization and treatment cost. Intention-to-treat analysis was used. Results: We found a statistically significant difference between the duration of hospitalization in the group risk-assessed at 72 hours and control group (p<0.01). “Delayed Risk-categorization” correlated better with the duration of neutropenia, need for antibiotic change and episode outcome. Duration of hospitalization and per-episode median treatment cost were significantly less in the study group vs. control (p< 0.001). There was a significant tendency for blood cultures to cluster around the first 48 hours. Comparing the blood culture yield between patients treated in the hospital to those treated as outpatients after risk-assessment at 72 hours there was no statistically significant difference demonstrated [p=0.35].

Readmission rate after early discharge was 3.3%.

Conclusion: We conclude that pediatric febrile-neutropenic patients initially at considered at “high risk for sepsis” can be reevaluated at 72 hours for outpatient therapy. The practice of “Delayed Risk-Categoriztion” could be particularly useful to reduce the overall treatment costs, and duration of hospitalization. In addition, this practice could potenitally offer a superior quality of life.