HCMV infections after hematopoietic stem cell transplantation – diagnostic methods and importance of viral DNA level monitoring
Joanna Bocian 1 , Danuta Januszkiewicz-Lewandowska 2Abstract
HCMV infection is very common. The virus infects 30-90% of population. In immunocompromised patients effective elimination of the virus by immune system is limited by immunosuppressive therapy. Active hCMV infection after HSCT can lead to severe posttransplant complications, graft failure or even death. In addition to direct effects of hCMV infection the virus can cause indirect effects in transplant recipients such as increased immunosuppression or GvHD development/progression. Laboratory diagnostic of hCMV infections after HSCT is now routinely used. Fast and sensitive molecular methods that detect hCMV genetic material are found particularly useful. Quantitative methods, such as R-T PCR, enable identification of patients at high risk of developing hCMV disease and fast employment of appropriate prophylaxis or treatment. Moreover it allows precise monitoring of treatment efficiency and facilitates therapy – related decisions. In last years pre-emptive therapy, which depends on viral load molecular monitoring, significantly reduced morbidity and mortality of active hCMV infections in HSCT recipients. Selective prophylaxis approach enables reduction of patients treated with toxic antiviral therapy which is associated with delayed restoration of virus – specific immune response. Occurrence of symptomatic hCMV disease is still associated with high mortality among HSCT recipients. HCMV infection diagnosis requires further development. Quantitative methods should be unified and optimized.
References
- 1. Abu-Khader A., Krause S.: Rapid monitoring of immune reconstitutionafter allogeneic stem cell transplantation – a comparisonof different assays for the detection of cytomegalovirus-specific Tcells. Eur. J. Haematol., 2013; 91: 534-545
Google Scholar - 2. Boeckh M., Boivin G.: Quantitation of cytomegalovirus: methodologicaspects and clinical applications. Clin. Microbiol. Rev., 1998;11: 533-554
Google Scholar - 3. Crough T., Khanna R.: Immunobiology of human cytomegalovirus:from bench to bedside. Clin. Microbiol. Rev., 2009; 22: 76-98
Google Scholar - 4. Dieamant D.C., Bonon S.H., Peres R.M., Costa C.R., AlbuquerqueD.M., Miranda E.C., Aranha F.J., Oliveira-Duarte G., Fernandes V.C., DeSouza C.A., Costa S.C., Vigorito A.C.: Cytomegalovirus (CMV) genotypein allogeneic hematopoietic stem cell transplantation. BMCInfect. Dis., 2013, 13: 310
Google Scholar - 5. Dobrzańska J., Sawczuk-Chabin J., Warzocha K.: Rola wirusóww etiopatogenezie chłoniaków nieziarniczych. Onkol. Prakt. Klin.,2006; 2: 64-72
Google Scholar - 6. Dolan A., Cunningham C., Hector R.D., Hassan-Walker A.F., LeeL., Addison C., Dargan D.J., McGeoch D.J., Gatherer D., Emery V.C.,Griffiths P.D., Sinzger C., McSharry B.P., Wilkinson G.W., DavisonA.J.: Genetic content of wild-type human cytomegalovirus. J. Gen.Virol., 2004; 85, 1301-1312
Google Scholar - 7. Durlik M., Dęborska-Materkowska D., Grenda R., Kaliciński P.,Klinger M., Ołdakowska-Jedynak U., Rowiński W., Rutkowski B., ZembalaM.: Zalecenia Polskiego Towarzystwa Transplantacyjnego,Krajowego Konsultanta w dziedzinie Transplantologii Klinicznejdotyczące postępowania profilaktycznego i leczniczego w zakażeniuwirusem cytomegalii u biorców przeszczepów narządowych.Warszawa 2010. http://www.p-t-t.org/recommendations/form/idr/8 (14.05.2014)
Google Scholar - 8. Durlik M., Grenda R., Jędrzejczak W.W., Kaliciński P., Klinger M.,Ołdakowska – Jedynak U., Podlasin B., Rutkowski B., Waszczuk – GajdaA., Zembala M.: Zalecenia Polskiego Towarzystwa Transplantacyjnego,Krajowych Konsultantów w dziedzinie: TransplantologiiKlinicznej, Chorób Zakaźnych, Hematologii i Nefrologii dotyczącepostępowania profilaktycznego i leczniczego w zakażeniu wirusemcytomegalii. Nefrol. Dializoter. Pol., 2007; 11: 89-99
Google Scholar - 9. Erice A.: Resistance of human cytomegalovirus to antiviral drugs.Clin. Microbiol. Rev., 1999; 12: 286-297
Google Scholar - 10. Espy M.J., Uhl J.R., Sloan L.M., Buckwalter S.P., Jones M.F., VetterE.A., Yao J.D., Wengenack N.L., Rosenblatt J.E., Cockerill F.R.3rd,Smith T.F.: Real-time PCR in clinical microbiology: applications forroutine laboratory testing. Clin. Microbiol. Rev., 2006; 19: 165-256
Google Scholar - 11. Gerna G., Baldanti F., Lilleri D., Parea M., Alessandrino E., PaganiA., Locatelli F., Middeldorp J., Revello M.G.: Human cytomegalovirusimmediate-early mRNA detection by nucleic acid sequence-basedamplification as a new parameter for preemptive therapy in bonemarrow transplant recipients. J. Clin. Microbiol., 2000; 38: 1845-1853
Google Scholar - 12. Greijer A.E., Adriaanse H.M., Dekkers C.A., Middeldorp J.M.: Multiplexreal-time NASBA for monitoring expression dynamics of human cytomegalovirusencoded IE1 and pp67 RNA.J. Clin. Virol., 2002; 24: 57-66
Google Scholar - 13. Hakki M., Chou S.: The biology of cytomegalovirus drug resistance.Curr. Opin. Infect. Dis., 2011; 24: 605-611
Google Scholar - 14. James S.H., Prichard M.N.: The genetic basis of human cytomegalovirusresistance and current trends in antiviral resistanceanalysis. Infect. Disord. Drug Targets, 2011; 11: 504-513
Google Scholar - 15. Kaniuka S., Piekarska A., Grabarczyk P., Prejzner W., BieniaszewskaM., Kisielewska J., Brojer E., Zaucha J.M.: Określenie progowej liczbykopii wirusa CMV w reakcji PCR w czasie rzeczywistym wskazującejna aktywną replikację wirusową u chorych po allogenicznej transplantacjikomórek krwiotwórczych. Acta Haematol. Pol., 2009; 40: 659-671
Google Scholar - 16. Lin R., Liu Q.: Diagnosis and treatment of viral diseases in recipientsof allogeneic hematopoietic stem cell transplantation. J.Hematol. Oncol., 2013; 6: 94
Google Scholar - 17. Ljungman P.: CMV infections after hematopoietic stem celltransplantation. Bone Marrow Transplant., 2008; 42 (Suppl. 1):S70-S72
Google Scholar