The Effect of Cidofovir on Adenovirus Plasma DNA Levels in Stem Cell Transplantation Recipients without T Cell Reconstitution
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 m...
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| Published in | Biology of blood and marrow transplantation Vol. 21; no. 2; pp. 293 - 299 |
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| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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United States
Elsevier Inc
01.02.2015
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| Abstract | 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. |
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| AbstractList | 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. 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. 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. •Cidofovir is used to treat human adenovirus viremia in pediatric hematopoietic stem cell transplantation recipients.•Evaluation of the antiviral effect of cidofovir is biased by T cell reconstitution.•In the absence of T cells, cidofovir can mediate human adenovirus load stabilization.•Natural killer cell expansion during human adenovirus load reduction in the absence of T cells. |
| Author | Kollen, Wouter J.W Smiers, Frans J Lugthart, Gertjan Bresters, Dorine Bredius, Robbert G.M Lankester, Arjan C Jol-van der Zijde, Cornelia M van Tol, Maarten J.D Oomen, Marloes A Schilham, Marco W Ball, Lynne M Vermont, Clementien L |
| Author_xml | – sequence: 1 fullname: Lugthart, Gertjan – sequence: 2 fullname: Oomen, Marloes A – sequence: 3 fullname: Jol-van der Zijde, Cornelia M – sequence: 4 fullname: Ball, Lynne M – sequence: 5 fullname: Bresters, Dorine – sequence: 6 fullname: Kollen, Wouter J.W – sequence: 7 fullname: Smiers, Frans J – sequence: 8 fullname: Vermont, Clementien L – sequence: 9 fullname: Bredius, Robbert G.M – sequence: 10 fullname: Schilham, Marco W – sequence: 11 fullname: van Tol, Maarten J.D – sequence: 12 fullname: Lankester, Arjan C |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25464118$$D View this record in MEDLINE/PubMed |
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| Copyright | American Society for Blood and Marrow Transplantation 2015 American Society for Blood and Marrow Transplantation Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved. |
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| Keywords | Immune reconstitution Pediatrics Cidofovir Natural killer cells Human adenovirus Hematopoietic stem cell transplantation |
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| Snippet | Abstract Cidofovir is frequently used to treat life-threatening human adenovirus (HAdV) infections in immunocompromised children after hematopoietic stem cell... Cidofovir is frequently used to treat life-threatening human adenovirus (HAdV) infections in immunocompromised children after hematopoietic stem cell... |
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| SubjectTerms | 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 |
| Title | The Effect of Cidofovir on Adenovirus Plasma DNA Levels in Stem Cell Transplantation Recipients without T Cell Reconstitution |
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