Volume 38, Issue 6 e15375

ORIGINAL ARTICLE

Clinical and Economic Impact of CMV Infection in Allogeneic Hematopoietic Stem Cell Transplantation: Perspectives from a Middle-Income Nation

Gin Gin Gan,

Corresponding Author

Gin Gin Gan

[email protected]

Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

Correspondence: Gin Gin Gan ([email protected])

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Thevambiga Iyadorai,

Thevambiga Iyadorai

orcid.org/0000-0002-9258-620X

Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

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Noor Yuhyi Sulaiman,

Noor Yuhyi Sulaiman

Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

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Najihah Hussein,

Najihah Hussein

orcid.org/0000-0002-5025-7651

Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

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Hany Ariffin,

Hany Ariffin

Department of Pediatrics, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

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Gin Gin Gan,

Corresponding Author

Gin Gin Gan

[email protected]

Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

Correspondence: Gin Gin Gan ([email protected])

Search for more papers by this author

Thevambiga Iyadorai,

Thevambiga Iyadorai

orcid.org/0000-0002-9258-620X

Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

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Noor Yuhyi Sulaiman,

Noor Yuhyi Sulaiman

Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

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Najihah Hussein,

Najihah Hussein

orcid.org/0000-0002-5025-7651

Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

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Hany Ariffin,

Hany Ariffin

Department of Pediatrics, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

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First published: 21 June 2024

https://doi.org/10.1111/ctr.15375

Funding: This work was supported by grants from Merck Sharp & Dohme (MSD).

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ABSTRACT

Background

Cytomegalovirus infection (CMV) is a common complication after allogeneic hematopoietic stem cell transplantation (AHSCT). CMV infection increases transplantation costs; however, the extent of the financial burden may vary in different countries. This study aims to determine the clinical and economic impact of CMV infection in patients undergoing AHSCT in a middle-income country.

Methods

A total of 150 adult and pediatric patients post-AHSCT were included for analysis. In addition to incidence of CMV infections, data on graft versus host disease (GVHD) were also collected. Standard hospital charges for AHSCT and any additional transplantation-related expenditure within 12 months were also retrieved in 104 patients.

Results

CMV infection, acute GVHD and chronic GVHD occurred in 38.7%, 60.7%, and 22.0% of patients, respectively. Patients with CMV infections had higher readmission rates compared to those who did not (67.2% vs. 47.8%; p = 0.020). Additional expenditure was seen in HLA-haploidentical AHSCT and CMV infection (MYR11 712.25/USD2 504.49; p < 0.0001 and MYR5 807.24/USD1 241.79; p = 0.036), respectively.

Conclusion

This single-center study demonstrated that patients who underwent HLA-haploidentical AHSCT and subsequently developed CMV infection had higher transplantation expenditures compared to those who had matched-related transplantation. Further studies should be conducted to evaluate if primary prophylaxis against CMV is cost-effective, especially in patients who undergo HLA-haploidentical AHSCT.

Conflicts of Interest

The authors declare no conflicts of interest.

Open Research

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

References

1J. Styczynski, “Who is the Patient at Risk of CMV Recurrence: A Review of the Current Scientific Evidence with a Focus on Hematopoietic Cell Transplantation,” Infection Diseases and Therapeutics 7, no. 1 (2018): 1–16.
10.1007/s40121-017-0180-z
PubMed Web of Science® Google Scholar
2F. M. Marty, P. Ljungman, R. F. Chemaly, et al., “Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation,” The New England Journal of Medicine 377, no. 25 (2017): 2433–2444.
10.1056/NEJMoa1706640
CAS PubMed Web of Science® Google Scholar
3M. Boeckh and W. G. Nichols, “The Impact of Cytomegalovirus Serostatus of Donor and Recipient Before Hematopoietic Stem Cell Transplantation in the Era of Antiviral Prophylaxis and Preemptive Therapy,” Blood 103, no. 6 (2004): 2003–2008.
10.1182/blood-2003-10-3616
CAS PubMed Web of Science® Google Scholar
4A. Wong, K. H. Tan, C. S. Tee, and G. S. Yeo, “Seroprevalence of Cytomegalovirus, Toxoplasma and Parvovirus in Pregnancy,” Singapore Medical Journal 41, no. 4 (2000): 151–155.
CAS PubMed Google Scholar
5S. A. Ahmed, A. l-J. FS, A. W. Zaidah, et al., “The Prevalence of Human Cytomegalovirus Seropositivity Among Blood Donors at the Unit of Blood Transfusion Medicine, Hospital Universiti Sains Malaysia,” Southeast Asian Journal of Tropical Medicine and Public Health 37, no. 2 (2006): 294–296.
CAS PubMed Google Scholar
6P. L. Tan, L. M. Lim, C. Khanlian, and M. S. Villegas, “A Single-Center Experience of Cytomegalovirus Infections in Asian Pediatric Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant for Leukemia in Singapore,” Transplant Infectious Disease 16, no. 4 (2014): 556–560.
10.1111/tid.12238
CAS PubMed Web of Science® Google Scholar
7N. Y. Sulaiman, N. A. Anuar, N. Arshad, et al., “CMV Infection Post Allogeneic Hematopoietic Stem Cell Transplantation in a Resource Limited Country,” Indian Journal of Hematology and Blood Transfusion 40, no. 1 (2024): 97–102.
10.1007/s12288-023-01655-0
PubMed Web of Science® Google Scholar
8P. Teira, M. Battiwalla, M. Ramanathan, et al., “Early Cytomegalovirus Reactivation Remains Associated with Increased Transplant-Related Mortality in the Current Era: A CIBMTR Analysis,” Blood 127, no. 20 (2016): 2427–2438.
10.1182/blood-2015-11-679639
CAS PubMed Web of Science® Google Scholar
9N. Chuleerarux, S. Nematollahi, A. Thongkam, et al., “The Association of Cytomegalovirus Infection and Cytomegalovirus Serostatus with Invasive Fungal Infections in Allogeneic Haematopoietic Stem Cell Transplant Recipients: A Systematic Review and Meta-Analysis,” Clinical Microbiology and Infection 28, no. 3 (2022): 332–344.
10.1016/j.cmi.2021.10.008
CAS PubMed Web of Science® Google Scholar
10P. Ljungman, R. de la Camara, C. Robin, et al., “Guidelines for the Management of Cytomegalovirus Infection in Patients with Haematological Malignancies and After Stem Cell Transplantation from the 2017 European Conference on Infections in Leukaemia (ECIL 7),” The Lancet Infectious Diseases 19, no. 8 (2019): e260–e272.
10.1016/S1473-3099(19)30107-0
PubMed Web of Science® Google Scholar
11R. Ueno, S. Nishimura, G. Fujimoto, Y. Piao, and K. Takenaka, “The Clinical and Economic Burden of Cytomegalovirus Management Post Allogeneic Hematopoietic Stem Cell Transplantation in Japan—A Retrospective Database Study,” Current Medical Research and Opinion 35, no. 12 (2019): 2089–2096.
10.1080/03007995.2019.1649379
CAS PubMed Web of Science® Google Scholar
12A. Sepassi, I. M. Saunders, M. Bounthavong, R. A. Taplitz, C. Logan, and J. H. Watanabe, “Cost Effectiveness of Letermovir for Cytomegalovirus Prophylaxis Compared with Pre-Emptive Therapy in Allogeneic Hematopoietic Stem Cell Transplant Recipients in the United States,” PharmacoEconomics - Open 7, no. 3 (2023): 393–404.
10.1007/s41669-023-00398-y
PubMed Web of Science® Google Scholar
13A. Vyas, A. D. Raval, S. Kamat, K. LaPlante, Y. Tang, and R. F. Chemaly, “Real-World Outcomes Associated With Letermovir Use for Cytomegalovirus Primary Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients: A Systematic Review and Meta-analysis of Observational Studies,” Open Forum Infectious Diseases 10, no. 1 (2023): ofac687.
10.1093/ofid/ofac687
PubMed Web of Science® Google Scholar
14M. Kumar, M. Roychowdhury, J. Kumar, et al., “Cytomegalovirus Reactivation and Disease Amongst Patients with Allogeneic Haematopoietic Stem Cell Transplantation in Eastern India: Epidemiology, Outcome and Healthcare Cost,” Indian Journal of Medical Microbiology 36, no. 1 (2018): 49–53.
10.4103/ijmm.IJMM_17_269
PubMed Web of Science® Google Scholar
15C. Robin, F. Hémery, C. Dindorf, et al., “Economic Burden of Preemptive Treatment of CMV infection After Allogeneic Stem Cell Transplantation: A Retrospective Study of 208 Consecutive Patients,” BMC Infectious Diseases 17, no. 1 (2017): 747.
10.1186/s12879-017-2854-2
PubMed Web of Science® Google Scholar
16J. Schelfhout, H. Brown, J. A. House, and A. D. Raval, “Cytomegalovirus Infection and Associated Hospitalization and Costs Among Individuals Undergoing Allogeneic Hematopoietic Stem Cell Transplant,” Current Medical Research and Opinion 36, no. 1 (2020): 43–50.
10.1080/03007995.2019.1664827
PubMed Web of Science® Google Scholar
17T. S. Chan, S. S. Cheng, W. T. Chen, et al., “Cost-Effectiveness of Letermovir as Cytomegalovirus Prophylaxis in Adult Recipients of Allogeneic Hematopoietic Stem Cell Transplantation in Hong Kong,” Journal of Medical Economics 23, no. 12 (2020): 1485–1492.
10.1080/13696998.2020.1843321
PubMed Web of Science® Google Scholar
18H. M. Schoemans, S. J. Lee, J. L. Ferrara, et al., “EBMT-NIH-CIBMTR Task Force Position Statement on Standardized Terminology & Guidance for Graft-Versus-Host Disease Assessment,” Bone Marrow Transplant 53, no. 11 (2018): 1401–1415.
10.1038/s41409-018-0204-7
PubMed Web of Science® Google Scholar
19P. Ljungman, M. Boeckh, H. H. Hirsch, et al., “Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials,” Clinical Infectious Diseases 64, no. 1 (2017): 87–91.
10.1093/cid/ciw668
PubMed Web of Science® Google Scholar
20P. Ljungman and R. Brandan, “Factors Influencing Cytomegalovirus Seropositivity in Stem Cell Transplant Patients and Donors,” Haematologica 92, no. 8 (2007): 1139–1142.
10.3324/haematol.11061
PubMed Web of Science® Google Scholar
21M. Dziedzic, I. Sadowska-Krawczenko, and J. Styczynski, “Risk Factors for Cytomegalovirus Infection After Allogeneic Hematopoietic Cell Transplantation in Malignancies: Proposal for Classification,” Anticancer Research 37, no. 12 (2017): 6551–6556.
PubMed Web of Science® Google Scholar
22R. G. Rowe, D. Guo, M. Lee, S. Margossian, W. B. London, and L. Lehmann, “Cytomegalovirus Infection in Pediatric Hematopoietic Stem Cell Transplantation: Risk Factors for Primary Infection and Cases of Recurrent and Late Infection at a Single Center,” Biology of Blood and Marrow Transplantation 22, no. 7 (2016): 1275–1283.
10.1016/j.bbmt.2016.04.004
PubMed Web of Science® Google Scholar
23S. M. Heston, R. R. Young, J. S. Tanaka, et al., “Risk Factors for CMV Viremia and Treatment-Associated Adverse Events Among Pediatric Hematopoietic Stem Cell Transplant Recipients,” Open Forum Infectious Diseases 9, no. 2 (2022): ofab639.
10.1093/ofid/ofab639
PubMed Web of Science® Google Scholar
24T. H. Jaing, T. Y. Chang, S. H. Chen, et al., “Factors Associated with Cytomegalovirus Infection in Children Undergoing Allogeneic Hematopoietic Stem-Cell Transplantation,” Medicine (Baltimore) 98, no. 4 (2019): e14172.
10.1097/MD.0000000000014172
CAS PubMed Web of Science® Google Scholar
25B. Figgins, A. Hammerstrom, E. Ariza-Heredia, B. Oran, D. R. Milton, and J. Yeh, “Characterization of Viral Infections after Antithymocyte Globulin-Based Conditioning in Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation,” Biology of Blood and Marrow Transplantation 25, no. 9 (2019): 1837–1843.
10.1016/j.bbmt.2019.05.020
CAS PubMed Web of Science® Google Scholar
26T. Ara, Y. Hasegawa, H. Ohigashi, et al., “Low-Dose ATG has the Same Risk of CMV Reactivation after Allogeneic PBSCT as Ptcy, but Letemovir is Effective in Preventing CMV Reactivation,” Blood 142 (Supplement no. 1) (2023): 3546–3546.
10.1182/blood-2023-191306
Google Scholar
27S. R. Goldsmith, M. B. Abid, J. J. Auletta, et al., “Posttransplant Cyclophosphamide is associated With Increased Cytomegalovirus Infection: A CIBMTR Analysis,” Blood 137, no. 23 (2021): 3291–3305.
10.1182/blood.2020009362
CAS PubMed Web of Science® Google Scholar
28M. A. Khan, Q. Bashir, Q. U. Chaudhry, P. Ahmed, T. M. Satti, and S. K. Mahmood, “Review of Haploidentical Hematopoietic Cell Transplantation,” Journal of Global Oncology 4 (2018): 1–13.
Web of Science® Google Scholar
29M. Hakki, S. L. Aitken, L. Danziger-Isakov, et al., “American Society for Transplantation and Cellular Therapy Series: #3-Prevention of Cytomegalovirus Infection and Disease After Hematopoietic Cell Transplantation,” Transplantation Cellular Therapy 27, no. 9 (2021): 707–719.
10.1016/j.jtct.2021.05.001
PubMed Google Scholar
30F. Khawaja, A. Spallone, C. N. Kotton, and R. F. Chemaly, “Cytomegalovirus Infection in Transplant Recipients: Newly Approved Additions to our Armamentarium,” Clinical Microbiology and Infection 29, no. 1 (2023): 44–50.
10.1016/j.cmi.2022.07.001
CAS PubMed Web of Science® Google Scholar
31C. L. Jerry Teng, P. N. Wang, Y. C. Chen, and B. S. Ko, “Cytomegalovirus Management After Allogeneic Hematopoietic Stem Cell Transplantation: A Mini-Review,” Journal of Microbiology, Immunology, and Infection 54, no. 3 (2021): 341–348.
10.1016/j.jmii.2021.01.001
CAS Web of Science® Google Scholar
32 Household Income & Expenditure [Internet]. 2023. Available from: https://open.dosm.gov.my/dashboard/household-income-expenditure.
Google Scholar

Volume38, Issue6

June 2024

e15375

Clinical and Economic Impact of CMV Infection in Allogeneic Hematopoietic Stem Cell Transplantation: Perspectives from a Middle-Income Nation

ABSTRACT

Background

Methods

Results

Conclusion

Conflicts of Interest

Open Research

Data Availability Statement

References

References

Information

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Clinical and Economic Impact of CMV Infection in Allogeneic Hematopoietic Stem Cell Transplantation: Perspectives from a Middle-Income Nation

ABSTRACT

Background

Methods

Results

Conclusion

Conflicts of Interest

Open Research

Data Availability Statement

References

References

Related

Information