Cerebral aspergillus infection in pediatric acute lymphoblastic leukemia induction therapy
A 14-year-old boy with B-precursor acute lymphoblastic leukemia (ALL) presented to our emergency department with fever for 2 months, gum bleeding and breathlessness of 3 days duration. He was pale, dyspnic and hypotensive. In view of progressively worsening hypoxia, he was immediately put on assisted ventilation, inotropic support and intravenous antibiotics, including cephoperazone–sulbactam, amikacin and vancomycin. Baseline hemoglobin was 4.3 g/dL, white blood cell count 3900/mL and platelet count 14,000/mL, while the renal and liver function tests were normal. Chest radiograph showed bilateral lower zone consolidation. Antifungal prophylaxis was initiated with amphotericin B at a dose of 0.5 mg/kg on alternate days. Induction therapy for ALL was started with prednisolone and he was successfully extubated on Day 3. At this time, antileukemic therapy with steroids was continued and vincristine was administered. He developed hyperbilirubinemia of 7.8 mg/dL (direct bilirubin 6.2 mg/dL), aspartate transferase 46 IU/L, alanine transferase 121 IU/L and alkaline phosphatase 483 IU/L on Day 4, due to which daunorubicin and L-asparaginase were not administered. On Day 5 of induction therapy, he developed chest pain and aggravation of hypoxia. Chest radiograph showed bilateral multiple large nodular shadows predominantly in the lower lobes []. High-resolution computerized tomography (CT) of the chest showed bilateral multiple nodules surrounded by halo, suggestive of angioinvasive pulmonary aspergillosis []. Serum galactomannan ratio was positive at 3.0 (normal value <0.50). He was switched to daily therapy with amphotericin B at 1.5 mg/kg. On Day 7 of induction therapy, he developed unconsciousness with anisocoria, papilledema and a fixed right-sided gaze. Contrast-enhanced CT scan of the head showed multiple well-defined, enhancing, hypodense nodules in both cerebral hemispheres with perilesional edema [Figure and ], suggestive of CNS aspergillosis. Steroids, a predominant risk factor for invasive fungal infection, were withheld temporarily; additionally, the patient was administered decongestive therapy with mannitol. His condition deteriorated and he succumbed on Day 9 of induction. Postmortem lung biopsy showed vasoinvasive aggregates of fungal hyphal forms with septations and branching suggestive of aspergillosis [Figure and ], although a culture was not done. In view of CT findings of chest, a positive galactomannan assay and lung biopsy, it was a proven case of pulmonary aspergillosis with hematogenous dissemination to the brain.