The Effect of Cidofovir on Adenovirus Plasma DNA Levels in Stem Cell Transplantation Recipients without T Cell Reconstitution

• Published in: Biology of blood and marrow transplantation Vol. 21; no. 2; pp. 293 - 299
• Main Authors: Lugthart, Gertjan, Oomen, Marloes A, Jol-van der Zijde, Cornelia M, Ball, Lynne M, Bresters, Dorine, Kollen, Wouter J.W, Smiers, Frans J, Vermont, Clementien L, Bredius, Robbert G.M, Schilham, Marco W, van Tol, Maarten J.D, Lankester, Arjan C
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2015
• Subjects: Adenovirus Infections, Human - drug therapy; Adenovirus Infections, Human - immunology; Adenovirus Infections, Human - pathology; Adenovirus Infections, Human - virology; Adenoviruses, Human - drug effects; Adenoviruses, Human - immunology; Adolescent; Antiviral Agents - therapeutic use; Child; Child, Preschool; Cidofovir; Cohort Studies; Cytosine - analogs & derivatives; Cytosine - therapeutic use; DNA, Viral - antagonists & inhibitors; DNA, Viral - blood; Female; Hematology, Oncology and Palliative Medicine; Hematopoietic Stem Cell Transplantation; Human adenovirus; Humans; Immune reconstitution; Immunocompromised Host; Infant; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Lymphocyte Count; Lymphocyte Depletion; Male; Natural killer cells; Organophosphonates - therapeutic use; Pediatrics; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Transplantation, Homologous; Viral Load - drug effects; Viremia - drug therapy; Viremia - immunology; Viremia - pathology; Viremia - virology; Immune reconstitution; Pediatrics; Cidofovir; Natural killer cells; Human adenovirus; Hematopoietic stem cell transplantation
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2014.10.012

Abstract Cidofovir is frequently used to treat life-threatening human adenovirus (HAdV) infections in immunocompromised children after hematopoietic stem cell transplantation (HSCT). However, the antiviral effect irrespective of T cell reconstitution remains unresolved. Plasma HAdV DNA levels were monitored by real-time quantitative PCR during 42 cidofovir treatment episodes for HAdV viremia in 36 pediatric allogeneic HSCT recipients. HAdV load dynamics were related to T and natural killer (NK) cell reconstitution measured by flow cytometry. To evaluate the in vivo antiadenoviral effect of cidofovir, we focused on 20 cidofovir treatment episodes lacking concurrent T cell reconstitution. During 2 to 10 weeks of follow-up in the absence of T cells, HAdV load reduction (n = 7) or stabilization (n = 8) was observed in 15 of 20 treatments. Although HAdV load reduction was always accompanied by NK cell expansion, HAdV load stabilization was measured in 2 children lacking both T and NK cell reconstitution. In cases with T cell reconstitution, rapid HAdV load reduction (n = 14) or stabilization (n = 6) was observed in 20 of 22 treatments. In the absence of T cells, cidofovir treatment was associated with HAdV viremia control in the majority of cases. Although the contribution of NK cells cannot be excluded, cidofovir has the potential to mediate HAdV load stabilization in the time pending T cell reconstitution.