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. 2021 Apr;23(2):e13504.
doi: 10.1111/tid.13504. Epub 2020 Nov 29.

Unknown cytomegalovirus serostatus in primary immunodeficiency disorders: A new category of transplant recipients

Federica Forlanini  1   2 , Jasmeen Dara  1 , Christopher C Dvorak  1 , Morton J Cowan  1 , Jennifer M Puck  1 , Morna J Dorsey  1
Affiliations

Unknown cytomegalovirus serostatus in primary immunodeficiency disorders: A new category of transplant recipients

Federica Forlanini et al. Transpl Infect Dis. 2021 Apr.

Abstract

Background: Cytomegalovirus (CMV) serostatus of recipient (R) and donor (D) influences hematopoietic stem cell transplant (HSCT) outcome. However, it is not a reliable indicator of CMV infection in primary immunodeficiency disorder (PIDD) recipients who are unable to make adequate antigen-specific immunoglobulin (Ig) or who receive intravenous Ig (IVIg) prior to testing.

Objective: Since no data exist on PIDD with unknown CMV serostatus, we aimed to evaluate the relationship between pre-HSCT recipient and donor serostatus and incidence of CMV infection in recipients with unknown serostatus.

Methods: A retrospective analysis of all pediatric PIDD HSCTs (2007-2018) was performed at University of California San Francisco. Recipients were separated into categories based on pre-transplant serostatus: 1) seropositive (R(+)), 2) seronegative (R(-)), and 3) unknown serostatus (R(x)). Patients with pre-HSCT active CMV viremia were excluded.

Results: A total of 90 patients were included, 69% male. The overall incidence of CMV infection was 20%, but varied in R(+), R(-), and R(x) at 80%, 0%, and 14%, (P-value = .0001). Similarly, 5-year survival differed among groups, 60% R(+), 100% R(-), and 90% of R(x) (P-value = .0045). There was no difference in CMV reactivation by donor serostatus (P-value = .29), however, faster time to clearance of CMV was observed for R(x)/D(+) group (median 9.5 days (IQR 2.5-18), P-value = .024).

Conclusion: We identify a novel group of recipients, R(x), with an intermediate level of survival and CMV incidence post-HSCT, when compared to seropositive and seronegative recipients. No evidence of CMV transmission from D(+) in R(-) and R(x) was observed. We believe R(x) should be considered as a separate category in future studies to better delineate recipient risk status.

Keywords: Cytomegalovirus; hematopoietic stem cell transplant; infection; primary immunodeficiency; serostatus.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors have no conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Incidence of CMV infection by recipient serostatus: Kaplan-Meier graph showing the incidence of CMV infection (y) after HSCT (x) in seropositive category R(+), unknown serostatus R(x), and seronegative R(−)
FIGURE 2
FIGURE 2
Time to clearance of CMV infection: time in days to clearance of CMV infection in the unknown serostatus category R(x), compared between the two donor groups, D(+) and D(−)
FIGURE 3
FIGURE 3
Survival by CMV serostatus: Kaplan-Meier graph showing survival (y) at 5 years post-HSCT or at last follow-up (x) in seropositive R(+), seronegative R(−), and unknown serostatus R(x)
See this image and copyright information in PMC

References

    1. Chemaly RF, Chou S, Einsele H, et al. Definitions of resistant and refractory cytomegalovirus infection and disease in transplant recipients for use in clinical trials. Clin Infect Dis. 2018;68 (8):1420 −1426. - PMC - PubMed
    1. Zhou W, Longmate J, Lacey SF, et al. Impact of donor CMV status on viral infection and reconstitution of multifunction CMV-specific T cells in CMV-positive transplant recipients. Blood. 2009;113(25):6465–6476. - PMC - PubMed
    1. van der Heiden P, Marijt E, Falkenburg F, Jedema I. Control of cytomegalovirus viremia after allogeneic stem cell transplantation: a review on CMV-Specific T cell reconstitution. Biol Blood Marrow Transplant. 2018;24(9):1776–1782. - PubMed
    1. Emery V, Zuckerman M, Jackson G, et al. Management of cytomegalovirus infection in haemopoietic stem cell transplantation. Br J Haematol. 2013;162(1):25–39. - PubMed
    1. George B, Pati N, Gilroy N, et al. Pre-transplant cytomegalovirus (CMV ) serostatus remains the most impor tant determinant of CMV reactivation after allogeneic hematopoietic stem cell transplantation in the era of surveillance and preemptive therapy. Transpl Infect Dis. 2010;12(4):322–329. - PubMed

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