Invasive aspergillosis in pediatric patients

Abstract

This case-based review examines the growing literature on critical issues related to the epidemiology, diagnosis, and treatment of pediatric invasive aspergillosis. Immunocompromised children are at heightened risk for invasive aspergillosis. Children at highest risk include those with new-onset or relapsed hematologic malignancy and recipients of allogeneic stem cell transplants. Additional risk factors in stem cell transplant recipients include impaired lymphocyte engraftment and graft-versus-host disease. Pediatric invasive aspergillosis is associated with a high mortality rate (generally >50%) and requires prompt diagnosis and treatment to prevent dissemination and death. Tools available for diagnosis include radiologic examinations (primarily computed tomography), the galactomannan assay, bronchoalveolar lavage, and tissue biopsy. Age-related differences in computed tomography and galactomannan assay results have been suggested. Recommended primary therapy for pediatric invasive aspergillosis is voriconazole (7 mg/kg IV q12 hours). Currently approved alternative therapies include liposomal amphotericin B, amphotericin B lipid complex, and caspofungin. Posaconazole and itraconazole are also possibilities, but there is no established pediatric dose for posaconazole, and itraconazole dosing is difficult in children. In patients who do not benefit from initial antifungal therapy, options include switching to another agent with a different mechanism of action or combination therapy. Further research is required to better establish optimal approaches to the management of pediatric patients with invasive aspergillosis recalcitrant to initial primary therapy.

Key words::

• Acute myeloid leukemia
• Antifungal
• Bone marrow transplant
• Galactomannan assay
• Graft-versus-host disease
• Neutropenia

Transparency

Declaration of funding

This activity is supported by an educational grant from Merck & Co., Inc.

Declaration of financial/other relationships

W.J.S. has disclosed that he has received consulting fees from, and has contracted research for, Astellas and Merck. In addition, he has disclosed that he has received fees for non-CME services from Merck and Pfizer.

Some peer reviewers receive honoraria from CMRO for their review work. Peer reviewer 1 has disclosed that he/she has received research grants from Children’s Cancer Foundation of Baltimore and is on speakers bureaus of Enzon Pharmaceuticals and Sigma Tau Pharmaceuticals. Peer reviewer 2 has no relevant financial relationships to disclose.

Acknowledgment

The authors of this supplement thank Global Education Exchange, LLC, for editorial support.