Successful treatment of invasive mould infection affecting lung and brain in an adult suffering from acute leukaemia

Abstract

We describe in detail a 67-yr-old woman who was treated with a cytostatic combination chemotherapy for newly diagnosed common-acute lymphoblastic leukaemia. At the end of induction therapy, the patient acquired invasive mould infection affecting lung and brain. The patient entered complete remission of her leukaemia. Treatment with liposomal amphotericin B was initiated along with surgical excision of the fungal brain abscess. Intrathecal instillation of amphotericin B deoxycholate was started using an Ommaya reservoir because of an anatomical connection between the postoperative cavity and the ventricle. Full dose cytostatic chemotherapy was continued with little delay. A computerised tomography scan of the chest performed 2 months later revealed no fungal abscesses. Magnetic resonance imaging of the brain did not reveal any fungal manifestation. During maintenance therapy/week 69, the patient relapsed from leukaemia. High doses of intravenous liposomal amphotericin B were administered prophylactically. The patient's leukaemia proved refractory to reinduction chemotherapy and the patient died from pneumonia 8 wk later. Post mortem microbiological investigation and histopathological examination of lung and brain tissue did not reveal any macroscopical or microscopical fungal manifestations. This case underlines the feasibility and successful application of combined antileukaemic, antifungal and surgical therapy in a patient with acute leukaemia.

CNS infections in patients with hematological disorders (including allogeneic stem-cell transplantation)—Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)

“…Intrathecal or intralesional administration of AmB has been repeatedly been applied to patients with CNS aspergillosis, but published data are limited to case reports [ DIII ] [ 243 , 244 ]. In addition, intrathecal D-AmB could cause chemical arachnoiditis and it is unlikely that sufficient drug concentration is achieved in infected brain tissues [ 245 ].…”

Novel modes of antifungal drug administration

“…One report describes its use in a neutropenic patient with an invasive mould infection thought to be Aspergillus in the brain [136]. The patient was initially treated with systemic liposomal amphotericin B 6 mg/kg/day but symptoms continued to worsen with the patient losing sensation in her right arm and leg.…”

“…Doses utilised in these reports range from a starting dose of 0.05 mg [140] to maximum doses of 1 mg [134,135]. Doses have been given as often as daily [135,136] but more commonly are given 1 -3 times weekly [134,138,139]. Amphotericin B is given by injecting the dose using a 23 -25 gauge hypodermic needle into the subcutaneous capsule [134].…”

“…The most frequently described reservoir is the Ommaya reservoir [134][135][136][137][138][139][140]. The Ommaya reservoir consists of a subcutaneous capsule that is placed into a 'cranial burr-hole', which can be connected to a ventricular catheter [134].…”