High weekly doses of liposomal amphotericin B as secondary prophylaxis after cerebral aspergillosis in a paediatric patient
In September 2010 a 6-years-old male child was diagnosed standard risk acute lymphoblastic leukaemia and treated according to the protocol BFM-ALL-2000 . In April 2011, during the intensive re-induction phase, he developed an IFI with lung and cerebral localisation. The galactomannan test yielded a value of 0.95 and a CT scan revealed several, bilateral nodular solid lesions compatible with a mould infection. A cerebral MRI showed at least two intraparenchymal lesions with concomitant ventriculitis and a biventricular obstructive hydrocephalus (A).\nThe abscess was drained and A. fumigatus isolated from the purulent material. Voriconazole was given under therapeutic drug monitoring in the blood and cerebro-spinal fluid (CSF) through an external ventricular catheter, with constant dose adjustments ().\nCaspofungin (70 mg/m2 as a first dose and subsequently 50 mg/m2/day) was also added to the treatment, as proposed by some authors , even if its CNS penetration is considered to be generally low , to provide an additional systemic protection. Caspofungin was stopped after 4 weeks and voriconazole treatment (8 mg/kg/q12 h) continued. A cerebral MRI carried out 3 months after start of antifungal treatment showed a marked reduction of the abscesses but at the same time the appearance of new possible intracranial lesions (B), which, however, regressed in the following MRI controls. With the IFI under control, the antileukemic therapy (Phase IIB) could be resumed in August 2011 under secondary prophylaxis with voriconazole at drug blood levels higher than 1.2 mg/L. In February 2012 the patient developed a voriconazole-related Steven–Johnson syndrome. The drug was thus stopped and L-AmB⁎ started at an initial dosage of 5 mg/kg/week, increased to 7.5 mg/kg/week after 7 days and further to 10 mg/kg/week for the rest of the maintenance therapy. During high dose L-AmB all intracranial lesions resolved without any evidence of side effects. The patient ended secondary prophylaxis in October 2012 after 8 months of treatment in total with high dose L-Amb and since then he is in good physical conditions, with no evident loss of cognitive functions or neurological impairment and negative repeated cerebral MRI and cerebral fluid investigations (C).