Cytomegalovirus Reactivation Is Associated with Increased Risk of Late-Onset Invasive Fungal Disease after Allogeneic Hematopoietic Stem Cell Transplantation: A Multicenter Study in the Current Era of Viral Load Monitoring

Michelle K. Yong, Michelle Ananda-Rajah, Paul U. Cameron, Orla C. Morrissey, Andrew Spencer, David Ritchie, Allen C. Cheng, Sharon R. Lewin, Monica Slavin

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Opportunistic infections such as cytomegalovirus (CMV) reactivation and invasive fungal disease (IFD) cause significant morbidity and mortality to recipients of hematopoietic stem cell transplant (HSCT). We aimed to characterize the risk and relationship of CMV reactivation post-HSCT to IFD in the current era of CMV viral load monitoring using highly sensitive plasma DNA. A multicenter, retrospective, cohort study was conducted of consecutive patients undergoing allogeneic HSCT from January 2006 to December 2010 in Melbourne, Australia. CMV reactivation was defined as detection of plasma CMV DNA ≥ 546 IU/mL or development of CMV disease. IFD was classified in accordance with current international consensus guidelines. Of the 419 study participants, the median age was 44 years (IQR, 34 to 54), and CMV reactivation occurred in 106 participants (25%) at a median time of 56 days (IQR, 45 to 79). Thirty-eight participants (9.1%) were identified with 41 cases of IFD (n = 22 proven, n = 8 probable, n = 11 possible) at a median time of 76 days (IQR, 24 to 344). The incidence of IFD was higher in participants with CMV reactivation compared with no CMV reactivation (15% versus 7%, P = .012). In a multivariate analysis CMV reactivation remained an independent risk factor for IFD (hazard ratio, 3.7; 95% CI, 1.6 to 8.5; P = .002). The cumulative incidence of all IFD in patients with and without CMV reactivation using a competing risk regression was a hazard ratio of 2.2 (95% CI, 1.2 to 4.1; P = .017) and for late-onset IFD was a hazard ratio of 3.95 (95% CI, 1.7 to 9; P = .001). The median time to IFD onset was longer in participants with than without CMV reactivation (184 versus 37 days, P = .03). The peak viral load, detection of any level of viremia, and experiencing more than 1 episode of CMV reactivation were not associated with development of IFD. CMV reactivation in HSCT recipients in the post-transplant period is associated with an increased risk of developing late-onset IFD. Further research is warranted to understand the interaction between these 2 important infectious complications.

Original languageEnglish
Pages (from-to)1961-1967
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume23
Issue number11
DOIs
Publication statusPublished - Nov 2017

Keywords

  • Cytomegalovirus
  • Immunocompromised
  • Infection
  • Invasive aspergillosis
  • Invasive fungal infection
  • Transplantation

Cite this

@article{7738575d18df4870bf05de40f4adbfc5,
title = "Cytomegalovirus Reactivation Is Associated with Increased Risk of Late-Onset Invasive Fungal Disease after Allogeneic Hematopoietic Stem Cell Transplantation: A Multicenter Study in the Current Era of Viral Load Monitoring",
abstract = "Opportunistic infections such as cytomegalovirus (CMV) reactivation and invasive fungal disease (IFD) cause significant morbidity and mortality to recipients of hematopoietic stem cell transplant (HSCT). We aimed to characterize the risk and relationship of CMV reactivation post-HSCT to IFD in the current era of CMV viral load monitoring using highly sensitive plasma DNA. A multicenter, retrospective, cohort study was conducted of consecutive patients undergoing allogeneic HSCT from January 2006 to December 2010 in Melbourne, Australia. CMV reactivation was defined as detection of plasma CMV DNA ≥ 546 IU/mL or development of CMV disease. IFD was classified in accordance with current international consensus guidelines. Of the 419 study participants, the median age was 44 years (IQR, 34 to 54), and CMV reactivation occurred in 106 participants (25{\%}) at a median time of 56 days (IQR, 45 to 79). Thirty-eight participants (9.1{\%}) were identified with 41 cases of IFD (n = 22 proven, n = 8 probable, n = 11 possible) at a median time of 76 days (IQR, 24 to 344). The incidence of IFD was higher in participants with CMV reactivation compared with no CMV reactivation (15{\%} versus 7{\%}, P = .012). In a multivariate analysis CMV reactivation remained an independent risk factor for IFD (hazard ratio, 3.7; 95{\%} CI, 1.6 to 8.5; P = .002). The cumulative incidence of all IFD in patients with and without CMV reactivation using a competing risk regression was a hazard ratio of 2.2 (95{\%} CI, 1.2 to 4.1; P = .017) and for late-onset IFD was a hazard ratio of 3.95 (95{\%} CI, 1.7 to 9; P = .001). The median time to IFD onset was longer in participants with than without CMV reactivation (184 versus 37 days, P = .03). The peak viral load, detection of any level of viremia, and experiencing more than 1 episode of CMV reactivation were not associated with development of IFD. CMV reactivation in HSCT recipients in the post-transplant period is associated with an increased risk of developing late-onset IFD. Further research is warranted to understand the interaction between these 2 important infectious complications.",
keywords = "Cytomegalovirus, Immunocompromised, Infection, Invasive aspergillosis, Invasive fungal infection, Transplantation",
author = "Yong, {Michelle K.} and Michelle Ananda-Rajah and Cameron, {Paul U.} and Morrissey, {Orla C.} and Andrew Spencer and David Ritchie and Cheng, {Allen C.} and Lewin, {Sharon R.} and Monica Slavin",
year = "2017",
month = "11",
doi = "10.1016/j.bbmt.2017.07.025",
language = "English",
volume = "23",
pages = "1961--1967",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier",
number = "11",

}

Cytomegalovirus Reactivation Is Associated with Increased Risk of Late-Onset Invasive Fungal Disease after Allogeneic Hematopoietic Stem Cell Transplantation : A Multicenter Study in the Current Era of Viral Load Monitoring. / Yong, Michelle K.; Ananda-Rajah, Michelle; Cameron, Paul U.; Morrissey, Orla C.; Spencer, Andrew; Ritchie, David; Cheng, Allen C.; Lewin, Sharon R.; Slavin, Monica.

In: Biology of Blood and Marrow Transplantation, Vol. 23, No. 11, 11.2017, p. 1961-1967.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Cytomegalovirus Reactivation Is Associated with Increased Risk of Late-Onset Invasive Fungal Disease after Allogeneic Hematopoietic Stem Cell Transplantation

T2 - A Multicenter Study in the Current Era of Viral Load Monitoring

AU - Yong, Michelle K.

AU - Ananda-Rajah, Michelle

AU - Cameron, Paul U.

AU - Morrissey, Orla C.

AU - Spencer, Andrew

AU - Ritchie, David

AU - Cheng, Allen C.

AU - Lewin, Sharon R.

AU - Slavin, Monica

PY - 2017/11

Y1 - 2017/11

N2 - Opportunistic infections such as cytomegalovirus (CMV) reactivation and invasive fungal disease (IFD) cause significant morbidity and mortality to recipients of hematopoietic stem cell transplant (HSCT). We aimed to characterize the risk and relationship of CMV reactivation post-HSCT to IFD in the current era of CMV viral load monitoring using highly sensitive plasma DNA. A multicenter, retrospective, cohort study was conducted of consecutive patients undergoing allogeneic HSCT from January 2006 to December 2010 in Melbourne, Australia. CMV reactivation was defined as detection of plasma CMV DNA ≥ 546 IU/mL or development of CMV disease. IFD was classified in accordance with current international consensus guidelines. Of the 419 study participants, the median age was 44 years (IQR, 34 to 54), and CMV reactivation occurred in 106 participants (25%) at a median time of 56 days (IQR, 45 to 79). Thirty-eight participants (9.1%) were identified with 41 cases of IFD (n = 22 proven, n = 8 probable, n = 11 possible) at a median time of 76 days (IQR, 24 to 344). The incidence of IFD was higher in participants with CMV reactivation compared with no CMV reactivation (15% versus 7%, P = .012). In a multivariate analysis CMV reactivation remained an independent risk factor for IFD (hazard ratio, 3.7; 95% CI, 1.6 to 8.5; P = .002). The cumulative incidence of all IFD in patients with and without CMV reactivation using a competing risk regression was a hazard ratio of 2.2 (95% CI, 1.2 to 4.1; P = .017) and for late-onset IFD was a hazard ratio of 3.95 (95% CI, 1.7 to 9; P = .001). The median time to IFD onset was longer in participants with than without CMV reactivation (184 versus 37 days, P = .03). The peak viral load, detection of any level of viremia, and experiencing more than 1 episode of CMV reactivation were not associated with development of IFD. CMV reactivation in HSCT recipients in the post-transplant period is associated with an increased risk of developing late-onset IFD. Further research is warranted to understand the interaction between these 2 important infectious complications.

AB - Opportunistic infections such as cytomegalovirus (CMV) reactivation and invasive fungal disease (IFD) cause significant morbidity and mortality to recipients of hematopoietic stem cell transplant (HSCT). We aimed to characterize the risk and relationship of CMV reactivation post-HSCT to IFD in the current era of CMV viral load monitoring using highly sensitive plasma DNA. A multicenter, retrospective, cohort study was conducted of consecutive patients undergoing allogeneic HSCT from January 2006 to December 2010 in Melbourne, Australia. CMV reactivation was defined as detection of plasma CMV DNA ≥ 546 IU/mL or development of CMV disease. IFD was classified in accordance with current international consensus guidelines. Of the 419 study participants, the median age was 44 years (IQR, 34 to 54), and CMV reactivation occurred in 106 participants (25%) at a median time of 56 days (IQR, 45 to 79). Thirty-eight participants (9.1%) were identified with 41 cases of IFD (n = 22 proven, n = 8 probable, n = 11 possible) at a median time of 76 days (IQR, 24 to 344). The incidence of IFD was higher in participants with CMV reactivation compared with no CMV reactivation (15% versus 7%, P = .012). In a multivariate analysis CMV reactivation remained an independent risk factor for IFD (hazard ratio, 3.7; 95% CI, 1.6 to 8.5; P = .002). The cumulative incidence of all IFD in patients with and without CMV reactivation using a competing risk regression was a hazard ratio of 2.2 (95% CI, 1.2 to 4.1; P = .017) and for late-onset IFD was a hazard ratio of 3.95 (95% CI, 1.7 to 9; P = .001). The median time to IFD onset was longer in participants with than without CMV reactivation (184 versus 37 days, P = .03). The peak viral load, detection of any level of viremia, and experiencing more than 1 episode of CMV reactivation were not associated with development of IFD. CMV reactivation in HSCT recipients in the post-transplant period is associated with an increased risk of developing late-onset IFD. Further research is warranted to understand the interaction between these 2 important infectious complications.

KW - Cytomegalovirus

KW - Immunocompromised

KW - Infection

KW - Invasive aspergillosis

KW - Invasive fungal infection

KW - Transplantation

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U2 - 10.1016/j.bbmt.2017.07.025

DO - 10.1016/j.bbmt.2017.07.025

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VL - 23

SP - 1961

EP - 1967

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

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ER -