Successful treatment of
hepatosplenic candidiasis in an elderly patient with acute myeloid
leukemia using liposomal daunorubicin and fluconazole
Gerlando Quintini, Vincenzo Barbera, Rocco Gambino, Vincenzo
Spadola, Viviana Minardi, and Guglielmo Mariani.
Division of Hematology and BMT Unit, University of Palermo, Italy
Correspondence: Gerlando Quintini, M.D., Divisione di Ematologia e
Unità TMO, Policlinico Universitario di Palermo, via del
Vespro 129, 90127 Palermo, Italy. Phone: international
+39-091-6554314 E-mail: gequint@tin.it
Abstract
Fungal infections are an increasing cause of morbidity and mortality in patients with haematological malignancies. The organism most often responsible are Candida spp., particurarly Candida Albicans. This report describes our experience in a 63-year-old man who developed symptoms of hepatosplenic candidiasis caused by Candida tropicalis after treatment for acute myeloid leukaemia (AML). The fungal infection was successfully controlled using fluconazole, and the patient has been disease-free for more than 11 months after antileukemic chemotherapy without any recurrence of Candida infections. Our experience suggests that AML and chemotherapy associated fungal infections can be controlled with an appropriate therapeutic regimen.
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Fungal infections are an increasing cause of morbidity and mortality in patients with haematological malignancies.1 Underlying malignancy, neutropenia, intensive chemotherapy, advanced age, parental nutrition, prolonged broad-spectrum-antibiotic treatment, and use of central venous catheters (CVC) are all known risk factors for these infections. Hepatosplenic candidiasis (HSC) is one kind of fungal infection that is increasingly observed in patients with haematological malignancies receiving chemotherapy. In a recent prospective study, hepatic or splenic abscesses were detected in 16/55 (29.1%) patients with newly diagnosed or relapsing AML during chemotherapy.2 Here we report a similar experience with a 63-years-old man suffering from acute myeloid leukaemia (M4 FAB). The patient was treated with liposomal daunorubicin (Daunoxome), at the dosage of 80 mg/m2 for 4 consecutive days in combination with cytosine arabinoside (Ara-C) at the dosage of 100 mg/m2 for 7 consecutive days according to Gimema experience.3 Prior to intensive chemotherapy, a CVC was positioned. Prophylactic antimicrobial treatment consisted of oral itraconazole. During the aplastic phase, the patient developed a fever unresponsive to amikacin (15 mg/kg/day), ceftazidime (6 gr/day) and teicoplanin (200 mg/day). All blood cultures were negative for microbiological infections. Intravenous amphotericin B (AmB) was empirically added after 9 days of ineffective antibiotic treatment. Despite the AmB treatment and concomitantly bone marrow recovery, an intermittent high fever continued for another 7 days. On day 29, a yeastlike organism was isolated from blood cultures and identified as C. tropicalis, a pathogen that is increasingly found in a variety of Candida infections, including disseminated candidiasis.4 An abdominal ultrasonography (US) revealed multiple hypoechogenic lesions in the spleen, and computerized tomography (CT) demonstrated multiple low-density areas. The CVC was removed, and intravenous fluconazole (400 mg/day) was administered. On day 42 the patient was finally apyrexic, the antifungal treatment was discontinued, and the patient was discharged. Ten days later, the patient was readmitted for a second course of antileukemic chemotherapy. The neutrophil count was 4.7x109/L and liver function was normal. However, a CT scan showed multiple low-density areas in the liver and spleen. A US-guided fine-needle liver biopsy was performed and histopathologic examination using the periodic acid-Schiff stain reaction revealed numerous fungal organism in the necrotic areas, subsequently identified as C. tropicalis. Therapy with intravenous fluconazole (400 mg/d) was therefore resumed. During the antileukemic treatment, including cytarabine and liposomial daunorubicin, abdominal US and CT showed progressive regression of the hepatic lesions. After 30 days of antifungal therapy, the patient was discharged and continued oral fluconazole (300 mg daily) at home on alternate days. Three months later the hepatic lesions were completely absent. The patient has been disease-free for more than 21 months after antileukemic chemotherapy without any recurrence of Candida infections. AML is associated with high mortality rates and the onset of HSC as a result of aggressive chemotherapy complicates the treatment of these patients, often affecting decisions about the course, doses, and regimens of chemotherapic agents. This report suggests that prolonged administration of fluconazole can be effective in treating HSC that has not resolved with AmB in patients with hematologic malignancies, and that chemotherapy can be successfully continued even in patients in whom HSC has developed before leukemia remission has been obtained.5,6 Nonetheless, extreme care in minimising exposure to those risk factors predisposing to fungal infections remains a crucial aspect of the management of these patients.
