Disseminated invasive aspergillosis patient with CML and GVHD

Submitted by: Michael on: 15 April 2013

Case number: 46

Summary:

A 30 year old male with chemotherapy refractory chronic myeloid leukaemia (CML) in blast crisis who underwent a peripheral blood stem cell transplant from a matched unrelated donor in May 2002. His immediate post transplant complications included persistent neutropenic fever for which liposomal amphotericin B (LAB) was given as empirical antifungal therapy, gram negative sepsis and engraftment syndrome which was treated high dose corticosteroids. Neutrophil recovery (>0.5×109/l) occurred on day 22.
Six weeks post transplant the patient developed biopsy proven grade 4 GVHD of the gut, which was treated with intra-arterial corticosteroids and Alemtuzumab. Antifungal prophylaxis was changed from fluconazole to itraconazole. A surveillance high resolution computerised tomographic (HRCT) scan at day +77 and showed a linear density with ground glass surround suggestive of possible invasive filamentous fungal infection and the patient was changed from itraconazole prophylaxis to treatment with voriconazole.
The GVHD was moderately refractory to treatment and all attempts to wean the corticosteroids were unsuccessful. Second line treatment of the GVHD was attempted using Etanercept. Etanercept was initially successful but on cessation of Etanercept GVHD reactivated and then despite increasing doses of corticosteroids the symptoms and histopathological findings continued to worsen.

Treatment of the lung lesion was complicated by dose-limiting toxicities with voriconazole (liver biopsy proven hepatotoxicity) and liposomal amphotericin B. Multiple trials with other antifungal regimens resulted in further drug-related toxicities. Further investigations with serial HRCT scans of the thorax revealed progression with the development of multiple other nodules and bronchoscopy was PCR positive for Aspergillus .
At day +199 a decision was made to move to palliation and the patient died on day 226 with gastrointestinal haemorrhage as the terminal event.

At autopsy the major findings were of disseminated aspergillosis, disseminated Varicella Zoster infection and GVHD of gut and liver. There was no evidence of relapsed CML.

Species (if applicable):

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