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1561. Outcomes of Resistant or Refractory CMV Infection in Recipients of Allogeneic Hematopoietic Cell Transplant

BACKGROUND: Resistant or refractory CMV infections are not well defined and may be associated with high morbidity and mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients. Suspicion of resistant CMV infections is usually based on suboptimal responses to antiviral agents. METHO...

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Autores principales: Artau, Annette, Aitken, Samuel L, Batista, Marjorie, Chaer, Firas El, Prayag, Amrita, Haddad, Lynn El, Mulanovich, Victor, Ariza-Heredia, Ella, Chemaly, Roy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252448/
http://dx.doi.org/10.1093/ofid/ofy210.1389
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author Artau, Annette
Aitken, Samuel L
Batista, Marjorie
Chaer, Firas El
Prayag, Amrita
Haddad, Lynn El
Mulanovich, Victor
Ariza-Heredia, Ella
Chemaly, Roy
author_facet Artau, Annette
Aitken, Samuel L
Batista, Marjorie
Chaer, Firas El
Prayag, Amrita
Haddad, Lynn El
Mulanovich, Victor
Ariza-Heredia, Ella
Chemaly, Roy
author_sort Artau, Annette
collection PubMed
description BACKGROUND: Resistant or refractory CMV infections are not well defined and may be associated with high morbidity and mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients. Suspicion of resistant CMV infections is usually based on suboptimal responses to antiviral agents. METHODS: We performed a single-center retrospective chart review (January 2010 to September 2017) of Allo-HCT recipients who had CMV genotypic testing performed for suspected antiviral resistance. Based on the results, we categorized patients as either having refractory CMV (defined as CMV viremia that fails to decrease after at least 2 weeks of appropriately dosed and delivered antiviral therapy; and in the absence of known genetic mutations to the available antiviral agents) or resistant CMV infection (defined as refractory infection with identification of genetic mutations in the UL97 and/or UL54 genes correlating with in vitro antiviral resistance). Primary outcome was all-cause mortality. RESULTS: CMV genotypic resistance analysis was performed in 97 patients. Of those, 23 had resistant (11 had UL54 gene, 10 had UL97 gene, and two had both UL54 and 97) and 74 had refractory CMV infections. The majority of patients had AML (53%), underwent matched unrelated donor transplantation (43%), and received ATG during conditioning (64%). Patients with resistant CMV infections had a greater number of prior episodes when compared with those with refractory infections and had a longer time from transplant to suspicion of resistance (P < 0.01; each). Overall, the incidence of CMV disease was 41% (25% vs. 58% affecting the lungs and 56% vs. 17% the GI tract, in resistant vs. refractory infections, respectively). All-cause mortality was 57% (61% resistant vs. 55% refractory) and CMV-attributable mortality was 11% (9% resistant vs. 12% refractory). CONCLUSION: Our data showed that resistant CMV infections are associated with a higher rate of CMV disease. However, both resistant and refractory CMV infections had increased all-cause mortality and similar CMV-attributable mortality. There was no difference in outcomes between allo-HCT recipients who had resistant or refractory CMV infections. New treatment strategies for resistant or refractory CMV infections are needed. DISCLOSURES: S. L. Aitken, Merck: Speaker’s Bureau, Consulting fee. E. Ariza-Heredia, Oxford Immunotec: Grant Investigator, Research grant. R. Chemaly, Merck: Consultant, Research grant; Chimerix: Consultant, Research grant; Novartis: Investigator, Research grant; Oxford Immunotec: Consultant, Research grant.
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spelling pubmed-62524482018-11-28 1561. Outcomes of Resistant or Refractory CMV Infection in Recipients of Allogeneic Hematopoietic Cell Transplant Artau, Annette Aitken, Samuel L Batista, Marjorie Chaer, Firas El Prayag, Amrita Haddad, Lynn El Mulanovich, Victor Ariza-Heredia, Ella Chemaly, Roy Open Forum Infect Dis Abstracts BACKGROUND: Resistant or refractory CMV infections are not well defined and may be associated with high morbidity and mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients. Suspicion of resistant CMV infections is usually based on suboptimal responses to antiviral agents. METHODS: We performed a single-center retrospective chart review (January 2010 to September 2017) of Allo-HCT recipients who had CMV genotypic testing performed for suspected antiviral resistance. Based on the results, we categorized patients as either having refractory CMV (defined as CMV viremia that fails to decrease after at least 2 weeks of appropriately dosed and delivered antiviral therapy; and in the absence of known genetic mutations to the available antiviral agents) or resistant CMV infection (defined as refractory infection with identification of genetic mutations in the UL97 and/or UL54 genes correlating with in vitro antiviral resistance). Primary outcome was all-cause mortality. RESULTS: CMV genotypic resistance analysis was performed in 97 patients. Of those, 23 had resistant (11 had UL54 gene, 10 had UL97 gene, and two had both UL54 and 97) and 74 had refractory CMV infections. The majority of patients had AML (53%), underwent matched unrelated donor transplantation (43%), and received ATG during conditioning (64%). Patients with resistant CMV infections had a greater number of prior episodes when compared with those with refractory infections and had a longer time from transplant to suspicion of resistance (P < 0.01; each). Overall, the incidence of CMV disease was 41% (25% vs. 58% affecting the lungs and 56% vs. 17% the GI tract, in resistant vs. refractory infections, respectively). All-cause mortality was 57% (61% resistant vs. 55% refractory) and CMV-attributable mortality was 11% (9% resistant vs. 12% refractory). CONCLUSION: Our data showed that resistant CMV infections are associated with a higher rate of CMV disease. However, both resistant and refractory CMV infections had increased all-cause mortality and similar CMV-attributable mortality. There was no difference in outcomes between allo-HCT recipients who had resistant or refractory CMV infections. New treatment strategies for resistant or refractory CMV infections are needed. DISCLOSURES: S. L. Aitken, Merck: Speaker’s Bureau, Consulting fee. E. Ariza-Heredia, Oxford Immunotec: Grant Investigator, Research grant. R. Chemaly, Merck: Consultant, Research grant; Chimerix: Consultant, Research grant; Novartis: Investigator, Research grant; Oxford Immunotec: Consultant, Research grant. Oxford University Press 2018-11-26 /pmc/articles/PMC6252448/ http://dx.doi.org/10.1093/ofid/ofy210.1389 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Artau, Annette
Aitken, Samuel L
Batista, Marjorie
Chaer, Firas El
Prayag, Amrita
Haddad, Lynn El
Mulanovich, Victor
Ariza-Heredia, Ella
Chemaly, Roy
1561. Outcomes of Resistant or Refractory CMV Infection in Recipients of Allogeneic Hematopoietic Cell Transplant
title 1561. Outcomes of Resistant or Refractory CMV Infection in Recipients of Allogeneic Hematopoietic Cell Transplant
title_full 1561. Outcomes of Resistant or Refractory CMV Infection in Recipients of Allogeneic Hematopoietic Cell Transplant
title_fullStr 1561. Outcomes of Resistant or Refractory CMV Infection in Recipients of Allogeneic Hematopoietic Cell Transplant
title_full_unstemmed 1561. Outcomes of Resistant or Refractory CMV Infection in Recipients of Allogeneic Hematopoietic Cell Transplant
title_short 1561. Outcomes of Resistant or Refractory CMV Infection in Recipients of Allogeneic Hematopoietic Cell Transplant
title_sort 1561. outcomes of resistant or refractory cmv infection in recipients of allogeneic hematopoietic cell transplant
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252448/
http://dx.doi.org/10.1093/ofid/ofy210.1389
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