A 23-year-old man with a history of severe aplastic anemia (SAA) underwent bone marrow transplantation from his HLA-haploidentical mother in January 2014.
The conditioning regimens consisted of busulphan cyclophosphamide and antithymocyte globulin (BUCY+ATG) (10).
Cyclosporine A (CsA) and short-term methotrexate (MTX) plus mycophenolate mofetil (MMF) were used as prophylaxis against graft-versus-host disease (GVHD) (11).
Standard measures were adopted for the prevention of infectious complications, which included fluconazole for antifungal prophylaxis and acyclovir to prevent herpes-related infections.
A hemogram revealed the reconstruction of granulocytes (ANC>0.5×109/L) on day +12 post-transplantation.
The patient developed grade II acute GVHD of the skin on day +42 post-transplantation.
This was treated by treatment with a standard-dose of methyl-prednisolone, which achieved a complete response (CR).
The patient's chronic GVHD (cGVHD) of the skin gradually progressed from day +100 post-transplantation and he was treated with prednisolone and CsA.
On day 120 post-transplantation, he complained of a cough and antibiotics were administered.
A blood analysis revealed the following: WBC, 2.34×109/L; ANC, 1.72×109/L; hemoglobin, 85 g/L; and platelets, 72×109/L.
Although both a chest computed tomography (CT) scan and tests for pathogens via routine culturing, including blood tests for Beta-D glucan (G-test) and Galactomannan (GM-test) were all negative, the patient's cough did not respond to antibiotics and we empirically initiated treatment with voriconazole (6 mg/kg/12h for the first day, followed by 4 mg/kg/12h).
Liver toxicity occurred during voriconazole treatment, thus the anti-fungal regimen was changed to micafungin (100 mg/d).
However, the persistent cough did not improve and hoarseness developed after two weeks of treatment - ulcers were then observed in the throat by laryngoscopy (Fig.1a).
The patient developed severe dyspnea in the following week when anti-infection and topical treatments were applied.
Fiberoptic bronchoscopy revealed an irregular, nodular material with white moss, which nearly obstructed the bronchus; however, chest CT imaging was negative (Fig.1b and c).
The histopathological examination of biopsy specimens revealed an Aspergillus species (Fig.1d).
The patient was diagnosed with pseudomembranous Aspergillus tracheobronchitis type ITBA based on the results of bronchoscopy and a pathological examination (12).
The antibiotic and micafungin treatments were ceased and liposomal amphotericin B (liposomal AmB) was administered daily at a target dose of 3 mg/kg.
The patient's serum creatinine level rose from 60.4 μmol/L to 168 μmol/L during the first 7 days of liposomal AmB treatment.
Due to progressive renal dysfunction, the anti-fungal regimen was switched to a combination of posaconazole (400 mg/12 h) and caspofungin [50 mg, daily (70 mg for the first dose)].
The combination therapy continued for 2 weeks, until the previous nodules in the throat completely disappeared under bronchoscopy (Fig.2a); however, a repeat chest CT scan showed progression (Fig.2b).
The symptom of dyspnea gradually progressed, thus fiberoptic bronchoscopy was performed to remove the obstructive material from the patient's airways once a week for two weeks.
All of the symptoms were relieved and the final chest CT scan showed negative results before the discontinuation of anti-fungal therapy, and all of the tests were negative for Aspergillus.
Posaconazole was administered as a secondary prophylactic treatment and the patient was discharged from hospital.
The patient is still being followed and remains free of any recurrence of invasive fungal infection.