Original Articles
Vol. 18 No. 1 (2026): Mediterranean Journal of Hematology and Infectious Diseases
https://doi.org/10.4084/MJHID.2026.078

RECIPIENT-TO-DONOR ANTI-CMV IGG RATIO AS A PREDICTOR OF CMV REACTIVATION AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: A CASE-CONTROL STUDY

Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: October 31, 2026
0
Views
0
Downloads
Cytomegalovirus, Allogeneic Hematopoietic Stem Cell Transplantation, IgG titer

Authors

Siwar Frigui
siwar.frigui92@gmail.com
https://orcid.org/0009-0003-5675-7969
Laboratories Department, National Bone Marrow Transplant Center, Tunis, Tunisia, Tunisia.
Salma Daly
Laboratories Department, National Bone Marrow Transplant Center, Tunis, Tunisia, Tunisia.
Samia Rekaia
Pediatrics Department, National Bone Marrow Transplant Center, Tunis, Tunisia, Tunisia.
Yosra Chebbi
Laboratories Department, National Bone Marrow Transplant Center, Tunis, Tunisia, Tunisia.
Hedia Bellali
Preventive and Community Medicine Department, Habib Thameur Hospital, Tunis, Tunisia, Tunisia.
Monia Ben Khaled
Pediatrics Department, National Bone Marrow Transplant Center, Tunis, Tunisia, Tunisia.
Monia Ouederni
Pediatrics Department, National Bone Marrow Transplant Center, Tunis, Tunisia, Tunisia.
Wafa Achour
Laboratories Department, National Bone Marrow Transplant Center, Tunis, Tunisia, Tunisia.

 

Background: Despite advances in diagnosis and treatment, cytomegalovirus (CMV) reactivation remains a serious complication following allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT). Our objectives were to explore the impact of pre-transplant anti-CMV IgG titers in both donor and recipient on the occurrence of post-transplant CMV reactivation and to determine a threshold titer that would allow for better stratification of the post-transplant reactivation risk.

Methods: We conducted a unicentric retrospective case-control study involving pediatric allo-HSCT recipients. All donors were related (genotypically identical or haploidentical). CMV reactivation was defined by a viral load ≥ 150 IU/ml in plasma. We included 24 cases (patients who had an episode of CMV reactivation in the first 100 days after HSCT) and 48 randomly selected controls (patients without CMV reactivation in the first 100 days after HSCT).

Results: In univariate analysis, factors associated with CMV reactivation were D-/R+ pre-transplant CMV serostatus (p=0.013), recipient anti-CMV IgG titer (p=0.012), R/D anti-CMV IgG ratio (p=0.049), HLA haploidentical related donor (p=0.0001), GvHD prophylaxis with combination of cyclosporin A, cyclophosphamide and mycophenolate mofetil (p=0.0001), acute GvHD (p=0.001) and corticosteroids (p=0.0001). Donor anti-CMV IgG titer was a protective factor (p=0.046). Multivariate analysis showed that male donor gender (adjusted OR=4.919; 95% CI (1.103 – 21.942); p=0.037), D-/R+ pre-transplant CMV serologic status (adjusted OR=6.874; 95% CI (1.372 – 34.444); p=0.019), recipient anti-CMV IgG titer (adjusted OR=1.005; 95% CI (1.000 – 1.010); p=0.033), HLA haploidentical related donor (adjusted OR=5.472; 95% CI (1.334 – 22.453); p=0.018) and acute GvHD (OR=7.116; 95% CI (1.770 – 28.604) ; p=0.006) were independent risk factors for CMV reactivation after allo-HSCT. ROC curve analysis showed that the optimal cut-off value to predict CMV reactivation was 113.75 AU/ml for the recipient anti-CMV IgG titer (Se=72.2%; Sp= 64.9%; AUC=0.701; p=0.016) and 1 for the R/D anti-CMV IgG ratio (Se=77.8%; Sp=78.4%; AUC=0.814; p<0.001). The prevalence of CMV reactivation was higher in patients with pre-transplant anti-CMV IgG titer >113.75 AU/mL (50% versus 16%; p= 0.002) and in those with R/D anti-CMV IgG ratio >1 (64% versus 15%; p<0.001).

Conclusion: In summary, we have shown that both pre-transplant anti-CMV IgG titer in the recipient and R/D anti-CMV IgG ratio were associated with the risk of CMV reactivation following allo-HSCT. Furthermore, a high pre-transplant anti-CMV IgG titer in the donor was associated with a lower incidence of reactivation. Our findings add to the published experiences that show that pre-HCT CMV serology titer impacts on post-HCT reactivation and warrants validation in larger multicenter cohorts.

Downloads

Download data is not yet available.

Citations

Crossref
Scopus
Google Scholar
Europe PMC
1. Marty FM, Ljungman P, Chemaly RF, Maertens J, Dadwal SS, Duarte RF, et al. Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation. N Engl J Med. 2017 Dec 21;377(25):2433–44.
2. Boeckh M, Ljungman P. How we treat cytomegalovirus in hematopoietic cell transplant recipients. Blood. 2009 Jun 4;113(23):5711–9.
3. Dziedzic M, Sadowska-Krawczenko I, Styczynski J. Risk Factors for Cytomegalovirus Infection After Allogeneic Hematopoietic Cell Transplantation in Malignancies: Proposal for Classification. Anticancer Res. 2017 Dec;37(12):6551–6.
4. Kawamura S, Nakasone H, Takeshita J, Kimura S ichi, Nakamura Y, Kawamura M, et al. Prediction of Cytomegalovirus Reactivation by Recipient Cytomegalovirus-IgG Titer before Allogeneic Hematopoietic Stem Cell Transplantation. Transplant Cell Ther. 2021 Aug 1;27(8):683.e1-683.e7.
5. Arcuri LJ, Schirmer M, Colares M, Maradei S, Tavares R, Moreira MCR, et al. Impact of Anti-CMV IgG Titers and CD34 Count Prior to Hematopoietic Stem Cell Transplantation from Alternative Donors on CMV reactivation. Biol Blood Marrow Transplant. 2020 Nov 1;26(11):e275–9.
6. Einsele H, Ljungman P, Boeckh M. How I treat CMV reactivation after allogeneic hematopoietic stem cell transplantation. Blood. 2020 May 7;135(19):1619–29.
7. Ariza-Heredia EJ, Nesher L, Chemaly RF. Cytomegalovirus diseases after hematopoietic stem cell transplantation: a mini-review. Cancer Lett. 2014 Jan 1;342(1):1–8.
8. Green ML, Leisenring W, Stachel D, Pergam SA, Sandmaier BM, Wald A, et al. Efficacy of a viral load-based, risk-adapted, preemptive treatment strategy for prevention of cytomegalovirus disease after hematopoietic cell transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2012 Nov;18(11):1687–99.
9. George B, Pati N, Gilroy N, Ratnamohan M, Huang G, Kerridge I, 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 Off J Transplant Soc. 2010 Aug 1;12(4):322–9.
10. Zhou W, Longmate J, Lacey SF, Palmer JM, Gallez-Hawkins G, Thao L, 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 Jun 18;113(25):6465–76.
11. Grob JP, Grundy JE, Prentice HG, Griffiths PD, Hoffbrand AV, Hughes MD, et al. Immune donors can protect marrow-transplant recipients from severe cytomegalovirus infections. Lancet Lond Engl. 1987 Apr 4;1(8536):774–6.
12. Ljungman P, Brand R, Einsele H, Frassoni F, Niederwieser D, Cordonnier C. Donor CMV serologic status and outcome of CMV-seropositive recipients after unrelated donor stem cell transplantation: an EBMT megafile analysis. Blood. 2003 Dec 15;102(13):4255–60.
13. Jaskula E, Dlubek D, Tarnowska A, Lange J, Mordak-Domagala M, Suchnicki K, et al. Anti-CMV-IgG positivity of donors is beneficial for alloHSCT recipients with respect to the better short-term immunological recovery and high level of CD4+CD25high lymphocytes. Viruses. 2015 Mar 23;7(3):1391–408.
14. Eberhardt KA, Jung V, Knops E, Heger E, Wirtz M, Steger G, et al. CMV-IgG pre-allogeneic hematopoietic stem cell transplantation and the risk for CMV reactivation and mortality. Bone Marrow Transplant. 2023 Jun;58(6):639–46.
15. Griffiths P, Reeves M. Pathogenesis of human cytomegalovirus in the immunocompromised host. Nat Rev Microbiol. 2021 Dec;19(12):759–73.
16. Linde GA, Hammarström L, Persson MA, Smith CI, Sundqvist VA, Wahren B. Virus-specific antibody activity of different subclasses of immunoglobulins G and A in cytomegalovirus infections. Infect Immun. 1983 Oct;42(1):237–44.
17. Goldstein G, Rutenberg TF, Mendelovich SL, Hutt D, Oikawa MT, Toren A, et al. The role of immunoglobulin prophylaxis for prevention of cytomegalovirus infection in pediatric hematopoietic stem cell transplantation recipients. Pediatr Blood Cancer. 2017 Jul;64(7).
18. Pouteil-Noble C, Touraine JL, Gibert R, Aymard M. [Clinical use of immunoglobulin titers of anti-cytomegalovirus antibodies]. Rev Fr Transfus Immunohematol. 1984 Jun;27(3):365–74.
19. Zhang P, Yang D, Tian J, Feng S, Jiang E, Han M. A clinical study of lyophilized intravenous human immunoglobulin containing high-titer cytomegalovirus-neutralizing antibody for the treatment of cytomegalovirus viremia after allogeneic hematopoietic stem cell transplantation. Ann Palliat Med. 2021 May;10(5):5533–40.

Ethics Approval

allogeneic hematopoietic stem cell transplantation, CMV reactivation, Recipient-to-donor anti-CMV IgG ratio

How to Cite



“RECIPIENT-TO-DONOR ANTI-CMV IGG RATIO AS A PREDICTOR OF CMV REACTIVATION AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: A CASE-CONTROL STUDY” (2026) Mediterranean Journal of Hematology and Infectious Diseases, 18(1), p. e2026078. doi:10.4084/MJHID.2026.078.
Copyright (c) 2026 Siwar Frigui, Salma Daly, Samia Rekaia, Yosra Chebbi, Hedia Bellali, Monia Ben Khaled, Monia Ouederni, Wafa Achour Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.