An Evaluation of Sequential Computed Tomography of the Chest in Management of Invasive Pulmonal Aspergillosis in Neutropenic Patients With Haematological Malignancies

The incidence of invasive pulmonary aspergillosis (IPA) is increasing in all parts of the world. Despite introduction of new antifungal agents for prophylaxis and treatment of IPA in the last decade, the outcome of patients with IPA is still unsatisfactory and needs improvement. Particularly, recent developments in diagnostic imaging, including introduction of high-resolution computed tomography (CT) into standard procedures, made a place for improvement of diagnosis of IPA.

Computed tomography of the chest is the optimal, recommended imaging procedure for diagnosis of pneumonia in febrile neutropenic patients and it is significantly superior to conventional chest X-ray. However, the method is associated with some difficulties mostly due to the broad spectrum of pathological findings in patients with IPA and their evolution over time. This has been described in retrospective studies on relatively small groups of patients. Prospective studies on larger populations are still missing, as well as studies on combination of different diagnostic modalities e.g. diagnostic imaging and microbiology.

We recently published the results of the clinical trial: "A Phase II Dose Escalation Study of Caspofungin in Patients with Invasive Aspergillosis" which used caspofungin doses of 70 to 200 mg daily for the first line treatment of IPA. The maximum tolerated dose was not reached, but response rates were impressive with complete plus partial responses accounting for 54.3% and overall mortality at 12-week follow-up as low as 28.3%. There was a tendency towards higher doses yielding higher response rates.

For the majority of these patients we obtained serial chest CT. So, for the first time a patient population is at hand, in which the kinetics of infiltrates over time can be described.

The main objective is to describe the pathological findings in chest CT performed sequentially in IPA patients while receiving effective antifungal therapy. The specific objectives are:

1. Characteristics of pathological findings in sequential chest CTs

• To describe the pathological findings (e.g. halo sign, air crescent sign and air consolidation) in sequential high resolution computed tomogrphy (HRCT) examinations
• To calculate the incidence of individual pathological findings in sequential CT examinations
• To calculate a total volume of fungal infiltrates in sequential CT examinations

2. Correlation of pathological findings in sequential CT with corresponding white blood count (WBC) and absolute neutrophil count (ANC)

• To correlate the appearance or disappearance of individual pathological findings with WBC and ANC
• To correlate the volume of fungal infiltrates in sequential CT examinations with WBC and absolute neutrophil count

3. Correlation of pathological findings in sequential CT with the serum galactomannan index

• To correlate the appearance or disappearance of individual pathological findings with the serum galactomannan index
• To correlate the volume of fungal infiltrates in sequential HRCT examinations with the serum galactomannan index

4. Correlation of pathological findings in sequential HRCT with outcome of IFI

• To correlate the appearance or disappearance of individual pathological findings with outcome of IFI
• To correlate the volume of fungal infiltrates in sequential HRCT examinations with outcome of IFI