The Role of PET-CT for the Diagnosis of Infections in Hemato-Oncological Patients with Persistent Febrile Neutropenia

Patients with hematological malignancies and prolonged febrile neutropenia are at high risk for bacterial and invasive fungal infections (IFIs). We aimed to evaluate the role of PET-CT for detection of such infections among these patients.

Prospective cohort study of patients with hematological malignancies given intensive conventional chemotherapy and hematopoietic-cell transplantation (HCT) at our center. All consecutive, consenting patients with neutropenia (<500/mm³) and persistent or breakthrough fever despite broad spectrum antibiotics (>5days) had a PET-CT examination. The CT component of the PET-CT was a contrast-enhanced diagnostic CT. Results were available to clinicians in real time. Blinded evaluation of chest and sinus CT and the full PET-CT scan (i.e.chest, sinus CT, abdominal CT, and FDG uptake) were compared with the final clinical diagnosis 30 days after neutropenia resolution, as determined by an expert panel consisting of a hematologist and an infectious diseases expert. Patients were included more than once in the study for different episodes of persistent febrile neutropenia and each episode could receive more than one diagnosis at 30 days. Episodes concluding in no documented infection or other pathological process were classified as fever of unknown origin (FUO).

Between January 2008 and January 2011, 91 PET-CT examinations were performed in 79 patients. Median age was 56 (range: 21–85) years. PET-CT was performed after a median of 10 days from last chemotherapy (range: 0–255). Patients were neutropenic for a median of 11 (range:1–100) days.

Most patients had acute leukemia (71 episodes), 7 patients underwent allogeneic HCT and 6 patients with lymphoma underwent autologous HCT.

The types and number of individual diagnoses are listed in the table. Of the 91 PET-CT examinations, 23 episodes had two or more diagnoses, most commonly a combination of bacterial and fungal infection. Of 28 microbiologically documented infections (MDIs), bacteremia was the diagnosis in 20 episodes, most commonly without a focal source. In the primary analysis we considered FUO as “no disease” and all else as “disease”.

The sensitivity to detect any infection or non-infectious pathology in chest/sinus CT, was 58.8% (60 /102 diagnoses). The respective sensitivity for PET- CT was 85.3% (87/102). The difference in sensitivity was 26.5% (95% confidence interval 21.4% to 31.6%), matched sample p<0.001. The specificities of CT and PET-CT were not significantly different, 66.7% (10/15 episodes of FUO) and 60% (9/15), respectively. Of note, all 7 proven or probable fungal infections were FDG- positive.

In 28 cases, PET-CT demonstrated findings which were not detected on chest/sinus CT (27.5% of diagnoses).These were mainly abdominal infections (as appendicitis, diverticulitis, etc.) and abscesses (perianal, splenic, etc.).

When we compared PET-CT to total body (chest, sinus and abdominal) CT, we found that 7 of these cases were found only on PETCT. The sensitivity of total body CT to detect disease was 78.4% (80/102).

PET-CT resulted in modifications of patients’ management in 46 (55%) cases. These included change in antibiotics (14 cases), change in antifungals (14), change in both (5), an invasive diagnostic procedure (7), a surgical procedure (appendectomy, 3) and abscess drainage (4).

PET-CT has a higher sensitivity with no loss of specificity compared to chest/sinus CT in patients with persistent febrile neutropenia. The increase in sensitivity afforded by PET-CT was mainly due to the addition of abdominal CT. Thus, PET-CT has a potential role for the diagnosis of infections in neutropenic patients with persistent fever.

No relevant conflicts of interest to declare.