Mucormycosis in children with hematological malignancies: results of a single-center study

Abstract

Objective. To assess the incidence rate, risk factors and treatment outcomes of mucormycosis in children with hematological malignancies in the large tertiary hematology/oncology center. Materials and Methods. A total of 16 children (9 males/7 females) with mucormycosis were enrolled in a single-center, retrospective study over the period of 2012–2018. All patients had an underlying diagnosis of acute leukemia. Mucormycosis was diagnosed at the different timepoints after chemotherapy (CT) or hematopoietic stem cell transplantation (HSCT) in 15 cases and before CT in 1 case. The diagnosis of mucormycosis was based on clinical, microbiological or histological results. The median patient’s age at the time of mucormycosis diagnosis was 7.7 years. Results. The average incidence of mucormycosis was 1.15%, while in 2018 the overall incidence was significantly increased to 4% (p = 0.039), primarily due to patients with acute myeloid leukemia (9.75%, р = 0.004). The main risk factors were prolonged neutropenia (median – 30 days) <0,5 × 109/L and lymphopenia <0,2 × 109/L after CT or HSCT. The median time from CT/HSCT to diagnosis of mucormycosis was 29 days (13 to 398 days). Mucormycosis developed while on treatment with voriconazole in 6 patients. Mucormycosis was diagnosed by histological examination in 87.5% (n = 14), whereas microbiological identification yielded positive results only in 50% of patients. The most common pathogen was Lichtheimia (Absidia) corymbifera (n = 5). Pulmonary and rhinoorbital forms were observed in 43% and 36%, respectively, followed by gastrointestinal form (21%). A total of 15 patients were treated with lipid or liposomal formulation of amphotericin B and its combination with posaconazole and/or echinocandins, followed by monotherapy with posaconazole (93%). Twelve patients (75%) underwent surgical intervention, and mortality rate in that group was significantly lower compared to group receiving antifungal therapy alone (33% vs 100%, р = 0.039). The overall survival was 41% ±15%, and the 6-week survival – 69% ±12%. Conclusions. Although mucormycosis is a rare event, its incidence was unexpectedly high in the large hematology/oncology center. Considering that the incidence of mucormycosis has risen in the recent years, more careful risk factors assessment and appropriate antifungal prophylaxis for immunocompromised children is needed. Invasive diagnostic methods are essential in establishing accurate and timely diagnosis. However, despite diagnostic and prophylactic measures, mucormycosis is unable to be prevented in some cases.

Keywords

• mucormycosis
• children
• acute leukemia
• amphotericin b
• posaconazole
• lichtheimia corymbifera