Evaluation of CMV DNA Antigenemia Status in Patients With Allogeneic Bone Marrow Transplant

Year 2024, Volume: 8 Issue: 2, 236 - 243, 31.05.2024

Merve Keskinkılıç Serıfe Solmaz Ahmet Şeyhanlı Özgür Appak Arzu Sayıner Hayri Özsan İnci Alacacıoğlu

https://doi.org/10.30621/jbachs.1075229

Abstract

Purpose: The risk of cytomegalovirus (CMV) reactivation following allogeneic hematopoietic stem cell transplantation (ASCT) reaches 30-50%, and there are numerous diagnostic tests to detect CMV replication. The most common tests used in this group of patients include 65kDa phosphoprotein (pp65) antigenemia immunofluorescence assay and nucleic-acid-based quantitative CMV-DNA polymerase chain reaction (qPCR).
Material and Methods: In this study, patients who underwent ASCT and developed CMV positivity from 2009 to 2016 in our hospital were evaluated retrospectively. The study included samples of the same patient with antigenemia and CMV-DNA qPCR test for up to 48 hours. The study aimed to determine the factors affecting CMV DNA antigenemia and compare CMV DNA PCR and pp65 antigenemia immunofluorescence assay.
Results: The results of 138 specimens of 39 patients who underwent ASCT were evaluated. The mean value of CMV PCR, which was positive for both tests, was 57.887 copies/ml (70- 1.213.633 copies/ml) and a significant correlation was found between the two tests and the positive samples (p = 0.018). The ROC analysis showed that 322 copies/ml CMV viral load in plasma corresponds to ≥1 antigen-positive cells/200 thousand leukocytes (Sensitivity: 68.5%; Specificity: 31.5%). CMV infection was observed in 32 samples; CMV DNA cut-off values of the reference according to CMV DNA PCR and antigenemia results, compared to the development of CMV infection, presented a significant correlation (p=0.004).
Conclusion: Although there is a common agreement between antigenemia and CMV DNA PCR tests, one should keep in mind that the sensitivity of antigenemia test is low especially in the neutropenic period.

Keywords

Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT), CMV Infection, CMV Antigenemia (pp65), CMV DNA PCR

Evaluation of CMV DNA Antigenemia Status in Patients With Allogeneic Bone Marrow Transplant

Abstract

References

• Leung, AY, Kwong YL. Haematopoietic stem cell transplantation: current concepts and novel therapeutic strategies. Br Med Bull. 2010; 93: 85-103.
• Ljungman P, Reusser P, de la Camara R,et al. Management of CMV infections: recommendations from the infectious diseases working party of the EBMT. Bone Marrow Transplant. 2004 Jun;33(11):1075-81.
• Zaia JA. Prevention and management of CMV-related problems after hematopoietic stem cell transplantation. Bone marrow transplantation, 2002; 29(8): 633-8.
• Özdemir E. Allojeneik Kök Hücre Nakli Sırasında Sitomegalovirüs Enfeksiyonlarının Tanı ve Tedavisindeki Gelişmeler THD, Hematolog 2011:1-1.
• Tombuloğlu M. Ege Üniversitesi Tıp Fakültesi, Hematoloji Bilim Dalı, İzmir, Sitomegalovirus Tanı Ve Tedavisi, 2011.
• Ross SA, Novak Z, Pati S, et al. Overview of the diagnosis of cytomegalovirus infection. Infect Disord Drug Targets. 2011 Oct;11(5):466-74.
• Yakushiji K, Gondo H, Kamezaki K, et al. Monitoring of cytomegalovirus reactivation after allogeneic stem cell transplantation: comparison of an antigenemia assay and quantitative real-time polymerase chain reaction. Bone Marrow Transplant. 2002 Apr;29(7):599-606.
• Sissons JGP, Bain M, Wills MR, et al. Latency and reactivation of human cytomegalovirus. J Infection 2002; 44: 73–77.
• Murray PR, Baron EJ. Manual of Clinical Microbiology, 9th ed. ASM Press: Washington DC, 2007; 9: 1549-1563.
• Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis 2002; 34: 1094-1097
• Quamruddin AO, Oppenheim BA, Guiver M et al. Screening for cytomegalovirus (CMV) infection in allogeneic bone marrow transplantation using a quantitative whole blood polymerase chain reaction (PCR) method: analysis of potential risk factors for CMV infection. Bone Marrow Transplant 2001; 27: 301–306.
• Einsele H, Hebart H, Kauffmann-Schneider C et al. Risk factors for treatment failures in patients receiving PCR-based preemptive therapy for CMV infection. Bone Marrow Transplant 2000; 25: 757–763.
• Boeckh M, Leisenring W, Riddell SR, et al. Late cytomegalovirus disease and mortality in recipients of allogeneic transplants: Importance of viral load and T cell immunity. Blood 2003; 101: 407-414.
• Schechter GP, Broudy VC, Williams ME (editors). American Society of Hematology Education Program Book. Orlando, Florida, ABD, 2001.
• Schulenburg A, Watkins-Riedel T, Greinix HT, et al. CMV monitoring after peripheral blood stem cell and bone marrow transplantation by pp65 antigen and quantitative PCR. Bone Marrow Transplant. 2001 Oct;28(8):765-8.
• Einsele H, Ehninger G, Steidle M et al. Lymphocytopenia as an unfavourable prognostic factor in patients with cytomegalovirus infection after bone marrow transplantation. Blood 1993; 82: 1672–1678.
• Gokahmetoglu S, Kaynar L, Altuntas F,et al. Detection and quantification of cytomegalovirus in bone marrow transplant recipients by real time PCR and pp65 antigenemia. Saudi Med J, 2008; 29(11): 1673– 1675.
• Ghaffari SH, Obeidi N, Dehghan M, et al. A Monitoring of cytomegalovirus reactivation in bone marrow transplant recipients by real-time PCR. Pathol Oncol Res, 2008; 14(4): 399– 409.
• Çolak D, Kazık M, Mutlu D, et al. Assessment Of Cytomegalovırus Load In Hematopoıetıc Stem Cell Transplant Recıpıents By Cmv Antıgenemıa And Two Dıfferent Real-Tıme Pcr Assays Akdeniz University, School Of Medicine, Antalya.
• Özkarataş E, Özbek A, Oğuz V, et al. Solid Organ Nakli Alıcılarında CMV Antijenemi Testi ve CMV-DNA PCR Sonuçlarının Karşılaştırılması, Mikrobiyol Bul 50 (1), 44-52.
• Breda G, Almeida B, Carstensen S, et al. Human cytomegalovirus detection by real-time PCR and pp65-antigen test in hematopoietic stem cell transplant recipients: a challenge in low and middle-income countries. Pathog Glob Health. 2013 Sep;107(6):312-9.