[Refractory or Resistant Cytomegalovirus Infections After Hematopoietic Stem Cell Transplantation: Diagnosis and Management]

Overview

Journal Zhonghua Xue Ye Xue Za Zhi

Specialty Hematology

Date 2025 Jan 2

PMID 39746704

Authors

X Y Zhang

E L Jiang

Affiliations

Soon will be listed here.

Abstract

Cytomegalovirus (CMV) infection is one of the most prevalent opportunistic infections after hematopoietic stem cell transplantation (HSCT). Prophylaxis and preemptive therapy have demonstrated promise in reducing the incidence of CMV infection and CMV disease, but the management of refractory/resistant (R/R) CMV infections after HSCT remains a challenge that significantly affects the prognosis of patients undergoing HSCT. Intolerance and resistance to antivirals are the primary reasons for developing refractory CMV infections. CMV DNA quantification PCR combined with CMV-specific cell-mediated immunity monitoring may help to optimize diagnosis and enable personalized management of R/R CMV infection. Novel antiviral drugs and other immunotherapies, including intravenous immunoglobulin and adoptive CMV T cell therapy, constitute an appealing option.

References

Erard V, Guthrie K, Seo S, Smith J, Huang M, Chien J . Reduced Mortality of Cytomegalovirus Pneumonia After Hematopoietic Cell Transplantation Due to Antiviral Therapy and Changes in Transplantation Practices. Clin Infect Dis. 2015; 61(1):31-9. PMC: 4542910. DOI: 10.1093/cid/civ215. View

Wang L, Peck R, Yin Y, Allanson J, Wiggs R, Wire M . Phase I safety and pharmacokinetic trials of 1263W94, a novel oral anti-human cytomegalovirus agent, in healthy and human immunodeficiency virus-infected subjects. Antimicrob Agents Chemother. 2003; 47(4):1334-42. PMC: 152490. DOI: 10.1128/AAC.47.4.1334-1342.2003. View

Meesing A, Germer J, Yao J, Gartner M, Digmann B, Razonable R . Differences in Duration and Degree of Cytomegalovirus DNAemia Observed With Two Standardized Quantitative Nucleic Acid Tests and Implications for Clinical Care. J Infect Dis. 2019; 221(2):251-255. DOI: 10.1093/infdis/jiz452. View

Fowler K, Mucha J, Neumann M, Lewandowski W, Kaczanowska M, Grys M . A systematic literature review of the global seroprevalence of cytomegalovirus: possible implications for treatment, screening, and vaccine development. BMC Public Health. 2022; 22(1):1659. PMC: 9435408. DOI: 10.1186/s12889-022-13971-7. View

Jinnouchi F, Mori Y, Yoshimoto G, Yamauchi T, Nunomura T, Yurino A . Incidence of refractory cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Int J Hematol. 2021; 115(1):96-106. DOI: 10.1007/s12185-021-03218-3. View

Liu J, Kong J, Chang Y, Chen H, Chen Y, Han W . Patients with refractory cytomegalovirus (CMV) infection following allogeneic haematopoietic stem cell transplantation are at high risk for CMV disease and non-relapse mortality. Clin Microbiol Infect. 2015; 21(12):1121.e9-15. DOI: 10.1016/j.cmi.2015.06.009. View

Hakki M, Aitken S, Danziger-Isakov L, Michaels M, Carpenter P, Chemaly R . American Society for Transplantation and Cellular Therapy Series: #3-Prevention of Cytomegalovirus Infection and Disease After Hematopoietic Cell Transplantation. Transplant Cell Ther. 2021; 27(9):707-719. DOI: 10.1016/j.jtct.2021.05.001. View

Raanani P, Gafter-Gvili A, Paul M, Ben-Bassat I, Leibovici L, Shpilberg O . Immunoglobulin prophylaxis in hematopoietic stem cell transplantation: systematic review and meta-analysis. J Clin Oncol. 2008; 27(5):770-81. DOI: 10.1200/JCO.2008.16.8450. View

Whitehurst C, Sanders M, Law M, Wang F, Xiong J, Dittmer D . Maribavir inhibits Epstein-Barr virus transcription through the EBV protein kinase. J Virol. 2013; 87(9):5311-5. PMC: 3624302. DOI: 10.1128/JVI.03505-12. View

10.

Khawaja F, Spallone A, Kotton C, Chemaly R . Cytomegalovirus infection in transplant recipients: newly approved additions to our armamentarium. Clin Microbiol Infect. 2022; 29(1):44-50. DOI: 10.1016/j.cmi.2022.07.001. View

11.

Cho S, Ar M, Machado C, Wu D, Singh I, Sandhu A . Epidemiology, treatment patterns, and disease burden of cytomegalovirus in hematopoietic cell transplant recipients in selected countries outside of Europe and North America: A systematic review. Transpl Infect Dis. 2023; 25(4):e14083. DOI: 10.1111/tid.14083. View

12.

Prakash K, Chandorkar A, Saharia K . Utility of CMV-Specific Immune Monitoring for the Management of CMV in Solid Organ Transplant Recipients: A Clinical Update. Diagnostics (Basel). 2021; 11(5). PMC: 8153332. DOI: 10.3390/diagnostics11050875. View

13.

Luo X, Chang Y, Huo M, Li D, Huang X . [Cytomegalovirus-specific T cells immune reconstitution after human leukocyte antigen matched sibling donor allogeneic bone marrow plus peripheral blood hematopoietic stem cell transplantation]. Zhonghua Xue Ye Xue Za Zhi. 2012; 33(8):605-9. View

14.

Shen M, Hong S, Wang J, Zhang X, Xu L, Wang Y . A Predicted Model for Refractory/Recurrent Cytomegalovirus Infection in Acute Leukemia Patients After Haploidentical Hematopoietic Stem Cell Transplantation. Front Cell Infect Microbiol. 2022; 12:862526. PMC: 8981086. DOI: 10.3389/fcimb.2022.862526. View

15.

Alsuliman T, Kitel C, Dulery R, Guillaume T, Larosa F, Cornillon J . Cytotect®CP as salvage therapy in patients with CMV infection following allogeneic hematopoietic cell transplantation: a multicenter retrospective study. Bone Marrow Transplant. 2018; 53(10):1328-1335. DOI: 10.1038/s41409-018-0166-9. View

16.

Hayden R, Tang L, Su Y, Cook L, Gu Z, Jerome K . Impact of Fragmentation on Commutability of Epstein-Barr Virus and Cytomegalovirus Quantitative Standards. J Clin Microbiol. 2019; 58(1). PMC: 6935903. DOI: 10.1128/JCM.00888-19. View

17.

Hirji I, Cocks K, Moreno-Koehler A, Sundberg A . Healthcare resource utilization of maribavir versus investigator-assigned therapy in transplant recipients with cytomegalovirus infection refractory (with or without genotypic resistance) to prior treatment: Exploratory analysis of the Phase 3.... Transpl Infect Dis. 2023; 25(3):e14064. DOI: 10.1111/tid.14064. View

18.

Mushtaq M, Shahzad M, Shah A, Chaudhary S, Zafar M, Anwar I . Impact of natural killer cells on outcomes after allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis. Front Immunol. 2022; 13:1005031. PMC: 9574024. DOI: 10.3389/fimmu.2022.1005031. View

19.

Duan Z, Zhang X, Liu Y, Li F, Shen H, Chen R . Risk factors and survival of refractory cytomegalovirus reactivation after allogeneic peripheral blood stem cell transplantation. J Glob Antimicrob Resist. 2022; 31:279-285. DOI: 10.1016/j.jgar.2022.10.009. View

20.

Nho D, Lee R, Cho S, Lee D, Kim E, Park S . Cytomegalovirus Infection after Allogeneic Hematopoietic Cell Transplantation under 100-Day Letermovir Prophylaxis: A Real-World 1-Year Follow-Up Study. Viruses. 2023; 15(9). PMC: 10536589. DOI: 10.3390/v15091884. View