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Multicenter Study
. 2012 Sep;18(9):1391-1400.
doi: 10.1016/j.bbmt.2012.02.008. Epub 2012 Mar 3.

Efficiency and risk factors for CMV transmission in seronegative hematopoietic stem cell recipients

Steven A Pergam  1 , Hu Xie, Ravinder Sandhu, Margaret Pollack, Jeremy Smith, Terry Stevens-Ayers, Valeria Ilieva, Louise E Kimball, Meei-Li Huang, Tracy S Hayes, Lawrence Corey, Michael J Boeckh
Affiliations
Multicenter Study

Efficiency and risk factors for CMV transmission in seronegative hematopoietic stem cell recipients

Steven A Pergam et al. Biol Blood Marrow Transplant. 2012 Sep.

Abstract

Cytomegalovirus (CMV) transmission via stem cells or marrow in CMV donor seropositive/recipient seronegative (D+/R-) hematopoietic cell transplantation (HCT) is surprisingly inefficient, and factors associated with transmission in these high-risk HCT recipients are unknown. In a retrospective cohort of D+/R- HCT recipients, cumulative incidence curve estimates were used to determine posttransplantation rates of CMV and multivariable Cox proportional models to assess risk factors associated with transmission. A total of 447 patients from 1995 to 2007 were eligible for enrollment. Overall, 85 of 447 (19.0%) acquired CMV at a median of 49 days (IQR 41-60) posttransplantation. CMV disease before day 100 occurred in 6 of 447 (1.3%) patients and in 7 of 447 (1.6%) after day 100. The donor graft, specifically the total nucleated cell count (adjusted hazard ratio [HR] 2.7; 95% confidence interval [CI], 1.4-4.7, P = .0002), was the only factor associated with CMV transmission in multivariable analyses. Notably, the source stem cells (marrow versus peripheral blood stem cell [PBSC]), screening method, and graft-versus-host disease (GVHD) were not associated with transmission. Thus, a highly cellular graft was the only identifiable risk factor associated with CMV transmission, suggesting that viral genomic content of the donor graft determines transmission efficiency in D+/R- HCT recipients.

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Conflict of interest statement

AUTHOR CONFLICT OF INTEREST STATEMENT

S.A.P. has received research support from Chimerix, Merck, Viropharma, and has been a consultant from Chimerix and Optimer Pharmaceuticals. M.J.B. has received research funding from Chimerix, Roche, Viropharma, and Vical and has been a consultant for Chimerix, Genentech, Roche, Vical, Novartis, Astellas, Boehringer Ingelheim, and Viropharma.

Figures

Figure 1
Figure 1
Schema of CMV screening and development of study subsets (n = 447). Abbreviations: AG, antigenemia; PCR, polymerase chain reaction; † treated for any AG, except a few cases that had both AG testing and PCR where patients were given preemptive therapy for positive PCR at varying levels, *patients given preemptive therapy at CMV PCR levels ≥500 copies/mL, except patients on ≥1 mg/kg of steroids who are started on treatment at a level of ≥100 copies/mL.
Figure 2
Figure 2
Cumulative incidence of CMV transmission by day 100 in a cohort of CMV D+/R− hematopoietic cell transplant recipients (n = 447). Abbreviations: CMV, cytomegalovirus; D+, donor positive; R−, recipient negative. Patients censored at date or last contact, and death and retransplantation were considered competing risks.
Figure 3
Figure 3
Cumulative incidence of CMV transmission detected in blood by testing method* and total nucleated count in graft (in quartiles) in a cohort of CMV D+/R− hematopoietic cell transplant recipients (n = 447). (A) CMV outcomes by testing method. Abbreviations: CMV, cytomegalovirus; D+, donor positive; R−, recipient negative; antigenemia = pp65 antigenemia testing; PCR, polymerase chain reaction testing. Patients censored at date or last contact, and death and retransplantation were considered competing risks. *This figure represents patients who had supplemental retrospective PCR testing to assure complete testing by both modalities. (B) CMV incidence by total nucleated count quartiles. Patients censored at date of last contact, and death and retransplantation were considered competing risks.
Figure 4
Figure 4
ROC analysis of total nucleated count and any CMV reactivation.* Abbreviations: ROC, receiver-operating curve; CMV, cytomegalovirus; AUC, area under the curve. *Any CMV reactivation includes both patients with shedding and disease only. Best sensitivity (64%) and specificity (59%) at TNC of 7.84 × 108.
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References

    1. Boeckh M, Nichols WG. The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy. Blood. 2004;103:2003–2008. - PubMed
    1. Nichols WG, Corey L, Gooley T, Davis C, Boeckh M. High risk of death due to bacterial and fungal infection among cytomegalovirus (CMV)-seronegative recipients of stem cell transplants from seropositive donors: evidence for indirect effects of primary CMV infection. J Infect Dis. 2002;185:273–282. - PubMed
    1. George B, Pati N, Gilroy N, et al. Pre-transplant cytomegalovirus (CMV) serostatus remains the most important determinant of CMV reactivation after allogeneic hematopoietic stem cell transplantation in the era of surveillance and preemptive therapy. Transpl Infect Dis. 2010;12:322–329. - PubMed
    1. Walker CM, van Burik JA, De For TE, Weisdorf DJ. Cytomegalovirus infection after allogeneic transplantation: comparison of cord blood with peripheral blood and marrow graft sources. Biol Blood Marrow Transplant. 2007;13:1106–1115. - PubMed
    1. Matthes-Martin S, Lion T, Aberle SW, et al. Pre-emptive treatment of CMV DNAemia in paediatric stem cell transplantation: the impact of recipient and donor CMV serostatus on the incidence of CMV disease and CMV-related mortality. Bone Marrow Transplant. 2003;31:803–808. - PubMed

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