Invasive Zygomycosis during Treatment for Acute Lymphoblastic Leukaemia – Management of Two Life Threatening Diseases

Background

Zygomycetes cause acute angioinvasive infections and have mortality rates > 60%, depending on underlying condition.

Case Presentation Summary

A 5-year-old patient with acute lymphoblastic leukaemia (ALL) under treatment according to AIEOP-BFM-ALL 2009 protocol developed suspected pulmonary mycosis. After stop of ALL treatment and initiation of antimycotic treatment with liposomal Amphothericin B (AmBisome) and Voriconazole the patient was transferred to our clinic. After admission, thoracoscopic biopsy was performed. Specimens showed fungal hyphae, fungal PCR (ITS/5,8S-PCR) and sequencing revealed Actinomucor elegans representing proven invasive zygomycosis according to EORTC criteria. Therefore, Voriconazole was switched to Posaconazole (15 mg/kg/d, target drug levels of 0.5-5 mg/l) and dosage of AmBisome was increased to 10 mg/kg. After 4 weeks without ALL treatment, an interval therapy with Methotrexate and 6-Mercaptopurine was administered for another month. Under continued antimycotic treatment with AmBisome, we reinitiated therapy according to the AIEOP-BFM-ALL 2009 protocol, completed block IIb and started maintenance therapy. Pulmonary zygomycosis was monitored every 2-6 months by thoracic MRI (avoiding radiation of CT) with additional intermittent thoracic CT and PET-CT scans. In long term, AmBisome dosages were reduced, and intervals were extended to every 3^rd day due to practicability and to reduce possible side effects during myelodepressive chemotherapy. ALL-treatment was terminated 22 months after diagnosis (2 months earlier than required) in order to improve immune system. Since flow-cytometry showed continuously diminished B- and T-cell fractions, AmBisome was given for another 7 months post ALL-treatment. Recent thoracic CT indicates further improvement with primarily signs of tissue scarring.

Learning Points/Discussion

Despite invasive pulmonary zygomycosis, ALL treatment has to be continued under intensive antimycotic therapy in order to control these two potentially lethal diseases. Thoracic imaging and immune monitoring help in guiding treatment decisions.