Impact of Cytomegalovirus Viral Load on Probability of Spontaneous Clearance and Response to Preemptive Therapy in Allogeneic Stem Cell Transplantation Recipients

Jose Camargo Galvis, Erik Kimble, Rossana Rosa, Luis A. Shimose, Maria X. Bueno, Nikeshan Jeyakumar, Michele I Morris, Lilian Abbo, Jacques Simkins-Cohen, Maritza C. Alencar, Cara Benjamin, Eric Wieder, Antonio Jimenez, Amer Beitinjaneh, Mark Goodman, John Byrnes, Lazaros Lekakis, Denise L Pereira, Krishna V Komanduri

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Abstract

The optimal viral load threshold at which to initiate preemptive cytomegalovirus (CMV) therapy in hematopoietic cell transplantation (HCT) recipients remains to be defined. In an effort to address this question, we conducted a retrospective study of 174 allogeneic HCT recipients who underwent transplantation at a single center between August 2012 and April 2016. During this period, preemptive therapy was initiated at the discretion of the treating clinician. A total of 109 patients (63%) developed CMV viremia. The median time to reactivation was 17 days (interquartile range, IQR, 7-30 days) post-HCT. A peak viremia ≥150 IU/mL was strongly associated with a reduced probability of spontaneous clearance (relative risk,.16; 95% confidence interval,.1-.27), independent of established clinical risk factors, including CMV donor serostatus, exposure to antithymocyte globulin, and underlying lymphoid malignancy. The median time to clearance of viremia was significantly shorter in those who started therapy at CMV <350 IU/mL (19 days; IQR, 11-35 days) compared with those who started antiviral therapy at higher viremia thresholds (33 days; IQR, 21-42 days; P =.02). The occurrence of treatment-associated cytopenias was frequent but similar in patients who started preemptive therapy at CMV <350 IU/mL and those who started at CMV >350 IU/mL (44% versus 57%; P =.42). Unresolved CMV viremia by treatment day 35 was associated with increased risk of therapeutic failure (32% versus 0%; P =.001). Achieving eradication of CMV viremia by treatment day 35 was associated with a 74% reduction in 1-year nonrelapse mortality (NRM) (adjusted hazard ratio [HR],.26; 95% confidence interval [CI],.1-.8; P =.02), whereas therapeutic failure was associated with a significant increase in the probability of 1-year NRM (adjusted HR, 26; 95% CI, 8-87; P <.0001). We conclude that among allogeneic HCT patients, a peak CMV viremia ≥150 IU/mL is associated with a >80% reduction in the probability of spontaneous clearance independent of ATG administration, CMV donor serostatus, and lymphoid malignancy, and is a reasonable cutoff for preemptive therapy. Delaying initiation of therapy until a CMV value ≥350 IU/mL is associated with more protracted CMV viremia, and unresolved viremia by treatment day 35 is associated with a significant increase in NRM.

Original languageEnglish (US)
Pages (from-to)806-814
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume24
Issue number4
DOIs
StatePublished - Apr 1 2018

Fingerprint

Stem Cell Transplantation
Viral Load
Cytomegalovirus
Viremia
Cell Transplantation
Therapeutics
Confidence Intervals
Mortality
Tissue Donors
Antilymphocyte Serum
Neoplasms
Retrospective Studies
Transplantation

Keywords

  • Antiviral therapy
  • Cytomegalovirus
  • Stem cell transplantation
  • Viremia

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

@article{98088ec487a740ba84a3f64f136cad26,
title = "Impact of Cytomegalovirus Viral Load on Probability of Spontaneous Clearance and Response to Preemptive Therapy in Allogeneic Stem Cell Transplantation Recipients",
abstract = "The optimal viral load threshold at which to initiate preemptive cytomegalovirus (CMV) therapy in hematopoietic cell transplantation (HCT) recipients remains to be defined. In an effort to address this question, we conducted a retrospective study of 174 allogeneic HCT recipients who underwent transplantation at a single center between August 2012 and April 2016. During this period, preemptive therapy was initiated at the discretion of the treating clinician. A total of 109 patients (63{\%}) developed CMV viremia. The median time to reactivation was 17 days (interquartile range, IQR, 7-30 days) post-HCT. A peak viremia ≥150 IU/mL was strongly associated with a reduced probability of spontaneous clearance (relative risk,.16; 95{\%} confidence interval,.1-.27), independent of established clinical risk factors, including CMV donor serostatus, exposure to antithymocyte globulin, and underlying lymphoid malignancy. The median time to clearance of viremia was significantly shorter in those who started therapy at CMV <350 IU/mL (19 days; IQR, 11-35 days) compared with those who started antiviral therapy at higher viremia thresholds (33 days; IQR, 21-42 days; P =.02). The occurrence of treatment-associated cytopenias was frequent but similar in patients who started preemptive therapy at CMV <350 IU/mL and those who started at CMV >350 IU/mL (44{\%} versus 57{\%}; P =.42). Unresolved CMV viremia by treatment day 35 was associated with increased risk of therapeutic failure (32{\%} versus 0{\%}; P =.001). Achieving eradication of CMV viremia by treatment day 35 was associated with a 74{\%} reduction in 1-year nonrelapse mortality (NRM) (adjusted hazard ratio [HR],.26; 95{\%} confidence interval [CI],.1-.8; P =.02), whereas therapeutic failure was associated with a significant increase in the probability of 1-year NRM (adjusted HR, 26; 95{\%} CI, 8-87; P <.0001). We conclude that among allogeneic HCT patients, a peak CMV viremia ≥150 IU/mL is associated with a >80{\%} reduction in the probability of spontaneous clearance independent of ATG administration, CMV donor serostatus, and lymphoid malignancy, and is a reasonable cutoff for preemptive therapy. Delaying initiation of therapy until a CMV value ≥350 IU/mL is associated with more protracted CMV viremia, and unresolved viremia by treatment day 35 is associated with a significant increase in NRM.",
keywords = "Antiviral therapy, Cytomegalovirus, Stem cell transplantation, Viremia",
author = "{Camargo Galvis}, Jose and Erik Kimble and Rossana Rosa and Shimose, {Luis A.} and Bueno, {Maria X.} and Nikeshan Jeyakumar and Morris, {Michele I} and Lilian Abbo and Jacques Simkins-Cohen and Alencar, {Maritza C.} and Cara Benjamin and Eric Wieder and Antonio Jimenez and Amer Beitinjaneh and Mark Goodman and John Byrnes and Lazaros Lekakis and Pereira, {Denise L} and Komanduri, {Krishna V}",
year = "2018",
month = "4",
day = "1",
doi = "10.1016/j.bbmt.2017.11.038",
language = "English (US)",
volume = "24",
pages = "806--814",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Impact of Cytomegalovirus Viral Load on Probability of Spontaneous Clearance and Response to Preemptive Therapy in Allogeneic Stem Cell Transplantation Recipients

AU - Camargo Galvis, Jose

AU - Kimble, Erik

AU - Rosa, Rossana

AU - Shimose, Luis A.

AU - Bueno, Maria X.

AU - Jeyakumar, Nikeshan

AU - Morris, Michele I

AU - Abbo, Lilian

AU - Simkins-Cohen, Jacques

AU - Alencar, Maritza C.

AU - Benjamin, Cara

AU - Wieder, Eric

AU - Jimenez, Antonio

AU - Beitinjaneh, Amer

AU - Goodman, Mark

AU - Byrnes, John

AU - Lekakis, Lazaros

AU - Pereira, Denise L

AU - Komanduri, Krishna V

PY - 2018/4/1

Y1 - 2018/4/1

N2 - The optimal viral load threshold at which to initiate preemptive cytomegalovirus (CMV) therapy in hematopoietic cell transplantation (HCT) recipients remains to be defined. In an effort to address this question, we conducted a retrospective study of 174 allogeneic HCT recipients who underwent transplantation at a single center between August 2012 and April 2016. During this period, preemptive therapy was initiated at the discretion of the treating clinician. A total of 109 patients (63%) developed CMV viremia. The median time to reactivation was 17 days (interquartile range, IQR, 7-30 days) post-HCT. A peak viremia ≥150 IU/mL was strongly associated with a reduced probability of spontaneous clearance (relative risk,.16; 95% confidence interval,.1-.27), independent of established clinical risk factors, including CMV donor serostatus, exposure to antithymocyte globulin, and underlying lymphoid malignancy. The median time to clearance of viremia was significantly shorter in those who started therapy at CMV <350 IU/mL (19 days; IQR, 11-35 days) compared with those who started antiviral therapy at higher viremia thresholds (33 days; IQR, 21-42 days; P =.02). The occurrence of treatment-associated cytopenias was frequent but similar in patients who started preemptive therapy at CMV <350 IU/mL and those who started at CMV >350 IU/mL (44% versus 57%; P =.42). Unresolved CMV viremia by treatment day 35 was associated with increased risk of therapeutic failure (32% versus 0%; P =.001). Achieving eradication of CMV viremia by treatment day 35 was associated with a 74% reduction in 1-year nonrelapse mortality (NRM) (adjusted hazard ratio [HR],.26; 95% confidence interval [CI],.1-.8; P =.02), whereas therapeutic failure was associated with a significant increase in the probability of 1-year NRM (adjusted HR, 26; 95% CI, 8-87; P <.0001). We conclude that among allogeneic HCT patients, a peak CMV viremia ≥150 IU/mL is associated with a >80% reduction in the probability of spontaneous clearance independent of ATG administration, CMV donor serostatus, and lymphoid malignancy, and is a reasonable cutoff for preemptive therapy. Delaying initiation of therapy until a CMV value ≥350 IU/mL is associated with more protracted CMV viremia, and unresolved viremia by treatment day 35 is associated with a significant increase in NRM.

AB - The optimal viral load threshold at which to initiate preemptive cytomegalovirus (CMV) therapy in hematopoietic cell transplantation (HCT) recipients remains to be defined. In an effort to address this question, we conducted a retrospective study of 174 allogeneic HCT recipients who underwent transplantation at a single center between August 2012 and April 2016. During this period, preemptive therapy was initiated at the discretion of the treating clinician. A total of 109 patients (63%) developed CMV viremia. The median time to reactivation was 17 days (interquartile range, IQR, 7-30 days) post-HCT. A peak viremia ≥150 IU/mL was strongly associated with a reduced probability of spontaneous clearance (relative risk,.16; 95% confidence interval,.1-.27), independent of established clinical risk factors, including CMV donor serostatus, exposure to antithymocyte globulin, and underlying lymphoid malignancy. The median time to clearance of viremia was significantly shorter in those who started therapy at CMV <350 IU/mL (19 days; IQR, 11-35 days) compared with those who started antiviral therapy at higher viremia thresholds (33 days; IQR, 21-42 days; P =.02). The occurrence of treatment-associated cytopenias was frequent but similar in patients who started preemptive therapy at CMV <350 IU/mL and those who started at CMV >350 IU/mL (44% versus 57%; P =.42). Unresolved CMV viremia by treatment day 35 was associated with increased risk of therapeutic failure (32% versus 0%; P =.001). Achieving eradication of CMV viremia by treatment day 35 was associated with a 74% reduction in 1-year nonrelapse mortality (NRM) (adjusted hazard ratio [HR],.26; 95% confidence interval [CI],.1-.8; P =.02), whereas therapeutic failure was associated with a significant increase in the probability of 1-year NRM (adjusted HR, 26; 95% CI, 8-87; P <.0001). We conclude that among allogeneic HCT patients, a peak CMV viremia ≥150 IU/mL is associated with a >80% reduction in the probability of spontaneous clearance independent of ATG administration, CMV donor serostatus, and lymphoid malignancy, and is a reasonable cutoff for preemptive therapy. Delaying initiation of therapy until a CMV value ≥350 IU/mL is associated with more protracted CMV viremia, and unresolved viremia by treatment day 35 is associated with a significant increase in NRM.

KW - Antiviral therapy

KW - Cytomegalovirus

KW - Stem cell transplantation

KW - Viremia

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UR - http://www.scopus.com/inward/citedby.url?scp=85044985963&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2017.11.038

DO - 10.1016/j.bbmt.2017.11.038

M3 - Article

VL - 24

SP - 806

EP - 814

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 4

ER -