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Granulocyte Transfusions for Invasive Fungal Infections Refractory to Conventional Treatment in Pediatric Liver
Anita Verma1,2, Sunitha Vimalesvaran2, Kanchan Rao3
1Department of Infection Sciences, King's College Hospital, London, UK.
Background:
Invasive fungal infections (IFI) remain a leading cause of mortality in liver transplant (LTX) patients with neutropenia. Hematopoietic growth factors and granulocyte transfusions (GTx) have been historically used in patients with neutropenia and after hematopoietic stem cell transplantation (HSCT) to treat IFI, but none thus far, in pediatric liver transplant recipients (PLTR).
Methods:
We evaluated the safety and effect of GTx for life-threatening IFI, refractory to conventional antifungal treatment, in PLTR with hepatitis-associated aplastic anemia (HAAA) at King's College Hospital, London. We also conducted a literature review of GTX use in neutropenic pediatric patients with IFI.
Results:
Two PLTR with HAAA, Case 1, 9-year-old male and Case 2, 6-year-old male received 6 weeks and 3 weeks of GTx. Both presented with acute liver failure requiring urgent LTX, complicated by bone marrow failure due to HAAA, multiple bacterial infections, and IFI. Case 1 developed invasive pulmonary aspergillosis (IPA), intra-abdominal (IAB) and bloodstream infection (BSI) with Candida guilliermondii and Candida fermentati whilst on four antifungals. Case 2 developed a necrotizing lesion on his arm, confirmed as mucormycosis, and had a BSI with Candida albicans and Candida glabrata whilst on two antifungals. Irradiated ABO group-compatible GTX was used as a bridge to control systemic dissemination of IFI. This provided some control in extremis until definitive treatment and improvement in neutrophil count by HSCT.
Conclusion:
These are the first two cases to report the use of GTx in PLTR with bone marrow failure due to HAAA. Both patients tolerated GTx without side effects. We propose the consideration of GTx as adjunctive therapy for life-threatening IFI refractory to conventional antifungals in PLTR with severe neutropenia.
Insights
Granulocyte transfusions (GTx) show promise as a safe adjunctive therapy for invasive fungal infections (IFI) in pediatric liver transplant recipients (PLTR) with neutropenia. This treatment offers a potential bridge to recovery in critical cases.
Area of Science:
- Hepatology
- Pediatric Hematology
- Infectious Diseases
Background:
- Invasive fungal infections (IFI) are a significant cause of mortality in pediatric liver transplant recipients (PLTR) with neutropenia.
- Conventional treatments for IFI in PLTR are often limited, especially in cases of bone marrow failure.
- Granulocyte transfusions (GTx) have a history of use in neutropenic patients but have not been previously reported in PLTR.
Observation:
- Two pediatric liver transplant recipients with hepatitis-associated aplastic anemia (HAAA) and life-threatening IFI refractory to antifungals received GTx.
- Case 1 presented with invasive pulmonary aspergillosis and bloodstream infections, while Case 2 had mucormycosis and bloodstream infections.
- GTx was administered as an adjunct to conventional antifungal therapy and served as a bridge to hematopoietic stem cell transplantation (HSCT).
Findings:
- Both PLTR tolerated GTx without reported side effects.
- GTx provided temporary control of systemic fungal dissemination in these critically ill patients.
- This study presents the first report of GTx use in PLTR experiencing bone marrow failure due to HAAA.
Implications:
- GTx may be considered a safe and potentially effective adjunctive therapy for severe, refractory IFI in PLTR with profound neutropenia.
- Further research is warranted to establish the role and optimal use of GTx in this vulnerable patient population.
- This approach could improve outcomes for PLTR facing life-threatening infections and bone marrow failure.
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