The burden of invasive infections in neutropenic patients: incidence, outcomes, and use of granulocyte transfusions

Abstract

Background: Patients with prolonged neutropenia caused by chemotherapy or underlying marrow disorders are at risk of invasive bacterial and fungal infections. New treatment options alongside targeted antimicrobial therapy that might improve outcomes include granulocyte transfusions (GTX). To inform the research agenda, a prospective observational cohort study was performed in the Netherlands and United Kingdom. The aim was to describe the incidence, characteristics, and outcomes of patients developing invasive infections and assess patients fulfilling criteria for GTX.

Study design and methods: All patients receiving myeloablative chemotherapy and anticipated to develop 7 or more days of neutropenia (<0.5 × 10⁹ /L) were eligible and followed for the development of invasive infections according to a defined algorithm and mortality up to 100 days. Secondary outcomes were types of infection and eligibility for GTX.

Results: A total of 471 patients enrolled at six hematology-oncology departments were followed for 569 neutropenic episodes. Overall, 32.5% of patients developed invasive infections during their first episode. Significant baseline risk factors for developing infections were high comorbidity scores (WHO performance status ≥ 2, hazard ratio [HR], 2.6 [1.7-3.9]; and hematopoietic cell transplantation-comorbidity index score ≥ 2 HR 1.3 [0.9-1.8]). Infections were bacterial (59.4%) and fungal (22.3%). Despite 34 patients (6.3% of all episodes) appearing to meet criteria to receive GTX, only nine patients received granulocytes. The HR for death was 5.8 (2.5-13.0) for patients with invasive infections.

Conclusion: This study documents that invasive infections are associated with significant mortality. There is a need for new strategies to prevent and treat infections, which may include better understanding of use GTX.

Figure 1

Patients with invasive infections in neutropenic episodes. Flow chart depicting all included patients with expected neutropenia of 7 days or longer and numbers of these patients developing invasive infections in the first neutropenic episode and in subsequent episodes. Numbers of patients who died are depicted.

Figure 2

Cumulative hazard of infections, AML patient. In this model‐based figure the cumulative hazard of infections with 95% confidence intervals is depicted for reference patients with AML. The model is presented in Table 4. Good risk is defined as a patient with AML and WHO comorbidity score 0 and HCT‐CI score of 0. Poor risk, WHO score 1, HCT‐CI ≥ 2.

Figure 3

Predicted survival in reference patients. Model‐based predicted survival is shown for reference patients with multiple myeloma (A) and with AML (B). The model is presented in Table 4. The solid lines show the predicted survival for patients who do not develop an infection. The dashed lines show how the survival probabilities change if the patients develop an infection at 6 days after start of neutropenia. Six days was chosen as this is the median time to develop invasive infections after start of neutropenia. Good risk is defined as patients with WHO comorbidity score 0 and HCT‐CI score of 0. Poor risk, WHO score 1, HCT‐CI ≥ 2.