A multicenter interventional trial using blood Mucorales PCR as a screening tool in high-risk hematology patients (MUCOPS)
Yuri Vanbiervliet, Robina Aerts, Ellen Boon, Kurt Beuselinck, Marijke Reynders, Toine Mercier, Alexander Schauwvlieghe, Katrien Lagrou, Johan MaertensAbstract
Background
Mucormycosis (MCM) is a life-threatening invasive mould infection. Patients with prolonged neutropenia or undergoing allogeneic hematopoietic cell transplantation (HCT) are at highest risk. Conventional diagnostics are insensitive, and no circulating antigen exists. Mucorales PCR shows promising diagnostic accuracy, and early blood PCR detection may improve diagnosis and survival. Prospective screening data remain limited.
Methods
MUCOPS was a prospective multicentre interventional study in Belgium. Adults receiving remission-induction chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome, or first allogeneic HCT, underwent twice-weekly serial plasma screening with a commercial Mucorales PCR assay (MucorGenius®), from treatment initiation until three months thereafter. The primary endpoints were the incidence of a positive Mucorales PCR screening result and the diagnostic performance of the assay. Results were reported within 24–48 hours and integrated into routine care, with performance evaluated against clinical, radiological, and microbiological data.
Results
Two hundred patients underwent 2400 plasma Mucorales PCR tests (median 9 tests per patient, IQR 6–17). A positive screening PCR occurred in 12 of 200 patients (6.0%). Five MCM cases (2.5%) were identified: three by plasma PCR and two plasma-PCR negative cases by BALF PCR only. Plasma PCR showed sensitivity 83.3%, specificity 99.6%, PPV 52.6% and NPV 99.9%. All five cases were PCR-detected and otherwise occult. Positive results triggered further investigations and early liposomal amphotericin B (median 1 day, IQR 0.5–2). Three patients had concomitant invasive aspergillosis. PCR clearance occurred within 4–7 days in survivors.
Conclusion
Twice-weekly plasma Mucorales PCR screening was feasible in high-risk hematology patients, with good sensitivity; excellent specificity and NPV, effectively ruling out MCM. Isolated BALF positivity highlights uncertain clinical significance. PCR detected otherwise occult MCM, enabled early antifungal therapy, and directly influenced clinical management. These findings support plasma Mucorales PCR for improved diagnosis and its incorporation into future definitions and management strategies.