Early low-dose computed tomography with pulmonary angiography to improve the early diagnosis of invasive mould disease in patients with haematological malignancies: A pilot study

Objective: High-resolution computed tomography (CT) is an essential diagnostic tool for invasive mould disease (IMD) in patients with haematological malignancies but is infrequently performed in the first 72 h of neutropenic fever until after chest X-ray (CXR). We hypothesised that early (< 48 h) low-dose CT (LD-CT; 90% reduction in radiation dose) combined with CT pulmonary angiography (CTPA) to detect the venous occlusion sign (VOS) inside suspected infiltrates could improve IMD diagnosis. Methods: We prospectively studied 68 consecutive adult patients undergoing treatment for haematological malignancies who developed fever following chemotherapy or haematopoietic stem cell transplantation. Within 48 h of fever, patients underwent a standard CXR followed by LD-CT imaging and CTPA if eligible based on baseline imaging findings; the same protocol was performed in 42/68 (61.7%) of patients at day 7 follow-up. The diagnostic performance of CT signs for EORTC/MSG-defined proven, probable, and possible IMD was analysed at both imaging periods. Results: The baseline LD-CT was positive for abnormalities in 43/68 (63%) of patients within 48 h of fever and 35/42 (83%) of patients at the follow-up exam. Amongst these 43 patients, CTPA was performed in 17/43 (39%) and in 18/35 (51%) at D + 7 follow-up. A positive VOS was associated with the highest estimated positive likelihood ratio for EORTC/MSG-defined proven, probable, or possible IMD at baseline (20.6; 95% CI 1.4–311.2) and at day 7 follow-up (19.0; 95% CI 0.93–300.8) followed by the baseline non-contrast enhanced hypodense sign (18.3; 0.93–361.7), reverse halo (11.0; 0.47–256.5), halo sign (8.68;3.13–24.01) and air-crescent sign at day 7 (16.7; 0.93–301.0). However, a negative VOS was the only CT sign at baseline or day 7 associated with sufficiently low negative likelihood ratio (0.05;0.001–0.8) to possibly support ruling-out IMD in patients with positive CT findings. Conclusions: Early LD-CT combined with CTPA shows promise for improving the early radiographic diagnosis of IMD.