Chronic Disseminated Candidiasis, Hematological Malignancies, Hematopoietic Stem Cell Transplantation, Invasive Fungal Disease, Neutropenia
Conditions
Keywords
Positron-Emission Tomography Scan, Fluorodeoxyglucose F18, Magnetic Resonance Imaging, Enzyme-Linked Immunospot Assay, Immune Reconstitution Inflammatory Syndrome, Real-Time Polymerase Chain Reaction, beta-1,3-D-glucan, Candida spp., Genetic Susceptibility, Genotype
Brief summary
The purpose of this study is to determine whether F18 fluorodeoxyglucose (18F-FDG) positron-emission tomography scan (PET scan) is useful for the therapy strategy of hepatosplenic candidiasis.
Detailed description
Chronic disseminated candidiasis, often referred to as hepatosplenic candidiasis (HSC), is an infection due to Candida spp. that mainly involves the liver and spleen. HSC occurs mostly in patients with profound and prolonged neutropenia, which is more often seen in patients with hematologic malignancies. Despite an appropriate antifungal prophylaxis, the incidence of HSC in France might be closed to 5% in patients suffering from acute leukemia. Early and adequate diagnosis and treatment of HSC are crucial, as treatment delays can negatively affect the prognosis of the underlying condition. Current guidelines recommend a 6-month duration treatment. Prolonged treatments up to 6 months are frequent, leading to antifungal toxicity and cost increase. Preliminary study by our team has already assessed F18 fluorodeoxyglucose (18F-FDG) positron-emission tomography scan (PET scan) as a diagnostic tool for HSC. 18F-FDG PET scan could be helpful in the diagnosis, follow-up and therapy strategy of HSC, helping to stop antifungal treatment. Other molecular, immunological and serological tools have to be developed in order to avoid hepatic biopsies. Actually, mycological evidence of infection is found in only 20% of the cases. The pathogenesis of HSC is also not well understood, but it is believed that it may be due to an unbalanced adaptive immune response that leads to an exacerbated inflammatory reaction, resulting in an Immune Reconstitution Inflammatory Syndrome (IRIS). In that context, a better understanding of the disease pathophysiology and of the potential genetic susceptibility could have an impact on therapy strategy. For example, new approaches such as the use of adjuvant high-dose corticosteroids have been shown beneficial. This study is the first step to improve HSC diagnosis and therapy strategy.
Interventions
DEVICE18F-FDG PET Scan
to determine whether F18 fluorodeoxyglucose (18F-FDG) positron-emission tomography scan (PET scan) is useful for the therapy strategy of hepatosplenic candidiasis.
Sponsors
University of Lausanne Hospitals
University Hospital, Lille
Institut Pasteur
Institut National de la Santé Et de la Recherche Médicale, France
URC-CIC Paris Descartes Necker Cochin
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Patients' inclusion criteria: * Adults aged ≥18 years-old * Hospitalized for hematological malignancy or hematopoietic stem cell transplantation * Recent (\>2months), prolonged (\>10 days), profound (\>100 PMN/mm3), feverish neutropenia * Suspected hepatosplenic candidiasis (typical small nodular lesions on abdominal RMI or CT) Patients'
Exclusion criteria
\- hepatosplenic lesions of other proven origin Patients' non-inclusion criteria: * Life expectancy \>3 months * Pregnancy * HIV infection * Hepatic biopsy within 3 weeks before 18F-FDG PET scan
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Global response to therapy | at month 3 | Clinical assessment (no fever) and PET scan assessment (intensity of liver and/or spleen lesions) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 18F-FDG PET scan and RMI usefulness in initial diagnosis | at month 3 | Comparison between Day 0 and Month 3 exams |
| Serological and molecular mycological tools assessment | at day 0 | Measurement of beta-1,3-D-glucans, mannan/anti-mannan, anti-Saccharomyces cerevisiae antibodies in comparison with controls. Assessment of a new real-time PCR on serum and hepatic tissue |
| Inflammatory cells and mediators | at day 0 | Measurement of cytokines and lymphocytes populations on serum and hepatic tissue in comparison with controls |
| Genetic susceptibility | at day 0 | Search for susceptibility genes to candidiasis in comparison with controls |
Countries
France
Outcome results
None listed