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. 2025 Feb;60(2):191-200.
doi: 10.1038/s41409-024-02389-x. Epub 2024 Nov 4.

Outcomes in hematopoetic cell transplantation in the setting of mold infections in patients with chronic granulomatous disease

Ahnika Kline #  1 , Mark Parta #  2 , Jennifer Cuellar-Rodriguez  3 , Juan Gea-Banacloche  3 , Corin Kelly  3 , Stefania Pittaluga  3   4 , Christa S Zerbe  3 , Steven M Holland  3 , Harry L Malech  3 , Elizabeth M Kang  3
Affiliations

Outcomes in hematopoetic cell transplantation in the setting of mold infections in patients with chronic granulomatous disease

Ahnika Kline et al. Bone Marrow Transplant. 2025 Feb.

Abstract

Chronic granulomatous disease (CGD) is a disorder of immunity characterized by phagocyte dysfunction. Mold infections in patients with CGD are often severe and disseminated. We present patient characteristics, microbiological data, and outcomes for 26 patients with CGD who received hematopoietic cell transplantation (HCT) or gene therapy-modified cells (GT) between 2008 and 2019, with proven fungal infection either before or during their transplant. All patients engrafted, and all but one GT recipient had neutrophil recovery and evidence of functional correction. Eighteen patients (69%) are currently alive and 19 patients (73% of total, 90% of patients with repeat imaging performed) had evidence of radiographic improvement. With 3 exceptions, deaths were not principally related to the fungal infection and duration of antecedent infection did not correlate with death. Aspergillus species accounted for the majority of disease (50%), followed by Phellinus species (18%). Osteomyelitis and disseminated disease were common, as only 11 patients (42%) had disease restricted to pneumonia. Triazole therapy was used in all 26 patients, with combination therapy used in 25 (96%). HCT or gene therapy, with appropriate antifungal therapy, are viable therapies for refractory fungal infections in patients with CGD.

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All participants signed written informed consent forms including consent to publish images. The patents were participants separate clinical trials, all of which were separately approved by the NIH Institutional Review Board (Approval numbers 16-I-0032, 000186-I, 19-I-0080). All procedures were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Figures

Fig. 1
Fig. 1. Representative radiology (left to right).
a Patient 13. a1 PET scans: 5 weeks prior to transplant (left), and 1 year post transplant (right). a2 CT scans. 5 weeks prior to transplant and (left) 3 years post transplant (right) b Patient 16. b1 PET scans: 10 weeks prior to transplant (left), and 1 year post transplant (right). b2 CT scans. 10 months post transplant (right), two months post transplant(left). Arrow indicates area of infection. c Patient 22. PET scans: 20 months prior to gene therapy (left), and 3 months post gene therapy (right).
Fig. 2
Fig. 2. Representative pathology imaging from 3 patients.
a Patient 13, 1 month prior to transplant. Soft tissue with granulation tissue with clusters of multinucleated giant cells and fungal forms present within giant cells (black arrows delineate giant cells, blue arrow shows fungal forms) a1 H&E (left) at 200x, GMS (right) at 400x, a2 H&E (below) at 400x b Patient 16, 3 months prior to transplant. Left upper lobe wedge. Marked granulomatous inflammation with neutrophilic abscess formation. Rare fungal forms are present within the abscess H&E (left) at 100x, GMS (right) at 400x c Patient 22, 3 years prior to gene therapy. Epidural lesion. Fibrous tissue with a dense lymphoplasmacytic infiltrate, multinucleated giant cells and rare fungal forms present. H&E (left), PAS (middle), GMS (right) at 200x.
See this image and copyright information in PMC

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