Azithromycin promotes relapse by disrupting immune and metabolic networks after allogeneic stem cell transplantation.

Administration of azithromycin after allogeneic hematopoietic stem cell transplantation for hematologic malignancies has been associated with relapse in a randomized phase 3 controlled clinical trial. Studying 240 samples from patients randomized in this trial is a unique opportunity to better understand the mechanisms underlying relapse, the first cause of mortality after transplantation. We used multi-omics on patients' samples to decipher immune alterations associated with azithromycin intake and post-transplantation relapsed malignancies. Azithromycin was associated with a network of altered energy metabolism pathways and immune subsets, including T cells biased toward immunomodulatory and exhausted profiles. In vitro, azithromycin exposure inhibited T-cell cytotoxicity against tumor cells and impaired T-cell metabolism through glycolysis inhibition, down-regulation of mitochondrial genes, and up-regulation of immunomodulatory genes, notably SOCS1. These results highlight that azithromycin directly affects immune cells that favor relapse, which raises caution about long-term use of azithromycin treatment in patients at high risk of malignancies. The ALLOZITHRO trial was registered at www.clinicaltrials.gov as #NCT01959100.

Diagnosis of an intestinal mucormycosis 'fungus ball' located with PET/CT with [18F] FDG-PET/CT.

Mucormycosis is a life-threatening infection with most commonly rhino-orbital-cerebral and pulmonary syndromes that mostly occurs in immunocompromised patients. FDG-PET/CT emerged as a sensitive non-invasive tool to identify systemic mucormycosis. We present a 59-year-old woman for whom a PET/CT with 18F-FDG was performed in search of a primary location of mucormycosis with non-contributive conventional workup. A large left abdominal mass was seen, compatible with a fungus ball, with intense parietal uptake and without any central uptake. The localization of the infection provided a target for surgery and permitted to adapt the therapeutic strategy. After resection, the final diagnosis was consistent with mucormycosis. To our knowledge, this is the first report of a PET/CT image with FDG showing an intestinal fungus ball. PET/CT with 18F-FDG may contribute to the management of patients with fungal infections of unknown origin.