Invasive Mucormycosis in Patients with Hematological Diseases Identified in the Global Fungiscope Registry

Background:

Invasive fungal diseases (IFD) are a frequent complication in hematological patients. Hematological malignancies and their treatment are main risk factors for IFD. Less frequent IFD, such as invasive mucormycoses (IM), are increasing worldwide and are associated with mortality up to 100%. Efficient diagnostic and treatment approaches for IM are not known or validated yet. Thus, it is urgent to better understand clinical presentation and management of IM in hematological patients to eventually improve patient outcome.

Methods:

Clinical data on IM were collected in FungiScope, an international web-based registry. Cases with cultural, histological or molecular evidence of IM are enrolled. Data collected include demographics, underlying conditions and their treatment, clinical signs and symptoms, sites of infection, diagnostic tests, antifungal treatment and outcome. Clinical isolates are collected for centralized identification, molecular analyses and exchange between collaborators.

Results:

To date, 194 cases of IM with an underlying hematologic disease (HD) were captured in the FungiScope database. AML, ALL, Non-Hodgkin's Lymphoma and CLL were the most frequent malignancies (50.5%, 16%, 5.6%, and 5.6%, respectively). Treatment of HD was chemotherapy in 76%, for 72% of these it was the primary course. Prolonged neutropenia (>10 days) was reported in 70% of cases (information available for 111 cases). The majority of patients received antifungal agents (94.3%; median 55 days, range 0 to 750 days) and 37% underwent surgical debridement. Antifungals known to be active against Mucorales (amphotericin B, isavuconazole, itraconazole, posaconazole) were administered in 82.5% of cases, in 16% of those amphotericin B was used as a single agent once the pathogen had been identified. Overall mortality was 62.4% and death due to IM was reported for 74% of cases. Mortality in patients receiving antifungals active against Mucorales was 56%. Median follow-up time was 45 days (range 0-2110 days). Favourable response (complete or partial response or stable disease) was present in 44% of all cases. Due to premature death, twelve patients did not receive antifungal therapy.

Conclusion:

The FungiScope registry is a feasible approach to collect data on a relevant amount of rare cases of rare IFD. IM remains a life threatening disease in hematological patients. Despite aggressive antifungal treatment strategies, outcome remains poor. More effective treatment strategies are urgently needed to improve patient outcome.