Clinical Characteristics and Treatment Response of Chronic Disseminated Candidiasis in Patients with Hematological Disorders
Authors: Chen Zhangjie , Feng Sizhou , Chen Xin , Jiang Erlie 
Published: December 2024

Background: Chronic disseminated candidiasis (CDC), also known as hepatosplenic candidiasis (HSC), is an invasive fungal infection typically affecting patients with hematological diseases and severe neutropenia, associated with increased mortality. However, there is a global shortage of clinical evidence on CDC.

Methods: We retrospectively analyzed clinical data from 49 CDC patients over the past decade. Clinical characteristics of primary hematological diseases, CDC diagnosis, treatment and response evaluations were included. Clinical factors associated with CDC remission and patient survival were analyzed.

Results: The majority of patients had hematological malignancies (n=43, 87.8%), including acute myeloid leukemia (n=21, 42.9%), acute lymphoblastic leukemia (n=18, 36.7%), myelodysplastic syndrome (n=2, 4.1%) and invasive B-cell lymphoma (n=2, 4,1%), and 27 patients (55.1%) had persistent severe neutropenia for more than 10 days prior to CDC. Symptoms were present in 85.7% of patients (n=42), and CT scans revealed liver lesions in 44 patients, spleen lesions in 34 patients, and kidney lesions in 9 patients. Proven, probable and possible CDC was diagnosed in 5 (10.2%), 2 (4.1%) and 42 patients (85.7%), respectively. Among the confirmed diagnoses, DNA sequencing identified 2 cases of Candida tropicalis and 1 case of Candida albicans infections, while the other 2 cases showed only positive microscopic examination of yeasts without a determined species. As for the treatment, azole monotherapy (n=16, 32.7%) and azole + echinocandin combination (n=12, 24.5%) were most commonly utilized, and more patients (n=28, 57.1%) were treated with antifungal monotherapy (azole=16, caspofungin=6, amphotericin=6) compared to combination regimens (n=21, 42.9%). Treatment outcomes at 3 months included 5 complete response (CR, 10.2%), 34 partial response (PR, 69.4%) and 10 treatment failure (20.4%). respectively. Caspofungin treatment showed a trend towards improving CR/PR rate, while severe neutropenia &gt; 20 days and proven diagnosis were significantly associated with 3-month treatment failure. Kaplan-Meier curve showed achieving CR/PR within 3 months did not significantly prolong OS compared to treatment failure patients (1197.6 days vs. 564.8 days, P=0.074). Additionally, no patient deaths were directly attributed to CDC infection. Age &gt; 45 years old and malignancy non-remission were prognostic factors of overall survival (OS). Furthermore, a prediction model identified severe neutropenia &gt; 20 days, proven/probable diagnosis and concomitant bacteremia as risk factors to effectively predict treatment failure. Also, patients with a risk score &lt; 0.203 in the model exhibited more rapid treatment response.

Conclusions: Our findings recommend CT scans for diagnosis and caspofungin as first-line therapy while continuing scheduled chemotherapy or bone marrow transplantation. Notably, risk factors identified by the prediction model could help predict treatment response. By providing clinical evidence from Chinese patients, our research could offer valuable insights for the broader Asia region and beyond, guiding future studies and enhancing clinical decision-making.