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CMV and its challenges

What is cytomegalovirus (CMV)?

CMV is a common beta virus that is a member of the herpes virus family.1 The prevalence in UK adults is estimated to be 50–60%.2

In immunocompetent individuals, the initial infection is generally asymptomatic but can present as flu-like symptoms.3 After the initial infection, the virus has the ability to establish lifelong latent infection.4 In immunocompromised individuals (such as those receiving transplants), new infection, reinfection with a different virus strain, or reactivation of the latent virus can result in serious complications and death.3,5

Consequently, CMV is one of the most common infections experienced by transplant recipients:

Estimated incidence rate of 16–56% in solid organ transplant (SOT) recipients5 Estimated incidence rate of 30–70% in haematopoietic stem cell transplant (HSCT) recipients6

CMV infection can progress to tissue-invasive disease and may alter the immune system: poor outcomes related to the direct and indirect effects of CMV7,8

Tissue invasive disease

Current challenges in post-transplant CMV

Managing vulnerable transplant patients can be a balancing act. Finding the right level of immunosuppression and treating complications such as emergent CMV infection, while trying to avoid additional treatment burden, adds complexity to post-transplant management.12,13

CMV considerations post-transplant

HSCT SOT
  • CMV infections after HSCT may increase the risk of other opportunistic infections, transplant failure and mortality14–16
  • CMV infections may become refractory to currently available treatments13
  • Refractory CMV infection poses significant clinical challenges because treatment options are limited and often associated with serious side effects13,17
  • Breakthrough CMV infections after SOT can significantly increase the risk of other opportunistic infections, graft rejection, and mortality8,10,18
  • CMV infections can become refractory to currently available treatment12
  • Refractory CMV infection comes with significant clinical challenges and an increased risk of non-relapse mortality compared to non-refractory12

Treating refractory CMV infections after transplant can be complicated by safety and tolerability issues. Experts call for new treatment options with specific focus on reducing toxicity without compromising potency.12,13,17

Identifying the risk factors of refractory CMV could support appropriate management:19–22

Risk Factors are Dynamic and Multi Factorial - graph implemented as an image (sorry)

CMV = cytomegalovirus; GvHD = graft-versus-host disease; HLA = human leukocyte antigen.

References:

  1. Crought T, Khanna R. Clin Microbiol Rev. 2009;22(1):76–98.
  2. NHS Blood and transplant. Factsheet. CMV negative blood components. 2018.
  3. Azevedo LS, et al. Clinics (Sao Paulo). 2015;70(7):515–23.
  4. Meesing A, Razonable RR. Drugs. 2018;78(11):1085–103.
  5. Styczynski J. Infect Dis Ther. 2018;7(1):1–16.
  6. Cho SY, et al. Int J Mol Sci. 2019;20(11):2666.
  7. Emery VC, et al. Lancet. 2000;355:2032–6.
  8. Jorgenson MR, et al. Transpl Infect Dis. 2019;21(3):e13080.
  9. Ljungman P, et al. Clin Infect Dis. 2017;64:87–91.
  10. Stern M, et al. Transplantation. 2014;98:1013–8.
  11. Robin C, et al. BMC Infect Dis. 2017;17:747.
  12. Kotton CN, et al. Transplantation. 2018;102:900–31.
  13. Ljungman P, et al. Lancet Infect Dis. 2019;19(8):e260–72.
  14. Yong MK, et al. BBMT. 2017;23(11):1961–7.
  15. Xiao Y, et al. Int J Med Sci. 2014;11(6):652–7.
  16. Hakimi Z, et al. Curr Res Transl Med. 2018;66(4):95–101.
  17. Khawaja F, et al. Clin Microbiol Infect. 2023;S1198-743X(22)00348–2.
  18. Hakimi Z, et al. Transpl Infect Dis. 2017;19(5):doi: 10.1111/tid.12732. Epub 2017 Jul 21.
  19. Fisher CE, et al. Clin Infect Dis. 2017;65:57–63.
  20. Liu J, et al. Clin Microbiol Infect. 2015;21(12):1121.e9–15.
  21. El Chaer F, et al. Blood. 2016;128:2624–36.
  22. Sandkovsky U, et al. Transplant Proc. 2018;50(10):3763–8.
Cytomegalovirus
Post-transplant (HSCT / SOT)
Disease Awareness
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C-ANPROM/GB/MARI/0087

July 2023