Granulocyte Transfusions for Invasive Fungal Infections Refractory to Conventional Treatment in Pediatric Liver Transplant Recipients With Hepatitis-Associated Aplastic Anemia.

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.