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Invasive and Allergic Complications Due to Aspergillus fumigatus in Allogeneic Hematopoietic Cell Transplantation (HCT) Primary Immunodeficiency (PID) Patients

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Introduction Invasive aspergillosis may complicate up to 23% of HCT. Three patients with predispositions to infection with Aspergillus pre-transplant underwent reduced intensity conditioning HCT for unrelated PIDs: hypomorphic IL2R-γ deficiency… Click to show full abstract

Introduction Invasive aspergillosis may complicate up to 23% of HCT. Three patients with predispositions to infection with Aspergillus pre-transplant underwent reduced intensity conditioning HCT for unrelated PIDs: hypomorphic IL2R-γ deficiency (36 y/o man, P1), STAT3 mutated Hyper IgE syndrome (7 y/o girl, P2), and EBV-associated lymphoproliferative disease with mutated IκBα (30 y/o woman, P3). Methods Conditioning consisted of pentostatin/cyclophosphamide (Cy); patients 2 and 3 also received busulfan, with high dose Cy/sirolimus/mycophenolate mofetil for GVHD prophylaxis. P1 and P2 received micafungin prophylaxis and P3 continued pre-HCT posaconazole. Results P1 had preexisting bronchiectasis colonized by Aspergillus fumigatus. The transplant was complicated by fever, mild hemoptysis and new nodular infiltrates during neutropenia. Blood Aspergillus antigen index (AAI) was positive 2 days prior to engraftment and negative day 31. On day 30, peripheral blood eosinophils rose to 4,640/µl (22.9%). Eosinophilia abated with corticosteroids for cutaneous GVHD, but tapering steroids was complicated by increasing eosinophilia and cough. Biopsy (day 59) of the new lung lesions revealed necrotizing inflammation and septate hyphae. P2 had a preexisting large right pneumatocele. Fevers persisted from day 3 post-HCT and beyond engraftment (day 19). Sputum cultures grew A. fumigatus. Eosinophilia on day 35 (560/µl, 12.5%) reached 2640/µl (29.9%) on day 45. Antifungal therapy was continued and corticosteroids and tocilizumab were given, with rapid abatement of fevers, cough and eosinophilia. The blood AAI was positive on day 54 but became negative by day 61. On day 94 a right pneumothorax developed. Resection of the affected lung was performed on day 114. P3 had a left lung cavity aspergilloma and intermittent hemoptysis prior to transplantation. HCT was successfully performed under posaconazole/isavuconazole prophylaxis. Post-HCT, cough was difficult to control, and eosinophilia appeared (460/µl, 13.9%) on day 48 coincident with new diffuse nodular infiltrates, interpreted as bronchial spread of the cavity contents. Right lung lavage revealed numerous neutrophils and eosinophils and grew A. fumigatus. The patient underwent left upper lobectomy on day 83. Symptoms and eosinophilia improved. Conclusion Three patients predisposed to Aspergillus disease underwent successful HCT for different PIDs, but each case was complicated by a mixed picture of invasive Aspergillus infection and eosinophilic inflammation similar to allergic bronchopulmonary aspergillosis. Successful management included aggressive antifungal therapy, but corticosteroids were necessary to manage the allergic symptoms, and lung resection was performed in two cases.

Keywords: lung; transplantation hct; aspergillus fumigatus; day; hct

Journal Title: Biology of Blood and Marrow Transplantation
Year Published: 2019

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