Front. Microbiol. Frontiers in Microbiology Front. Microbiol. 1664-302X Frontiers Media S.A. 10.3389/fmicb.2025.1518275 Microbiology Systematic Review Epidemiology, clinical outcomes, and treatment patterns of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in China: a scoping review and meta-analysis Lin Ren 1 Wu Jingyi 2 Liu Qifa 1 * 1Department of Hematology, Nanfang Hospital, Southern Medical University, Clinical Medical Research Center of Hematological Diseases of Guangdong Province, Guangzhou, China 2Medical Affairs, Takeda (China) International Trading Company, Shanghai, China

Edited by: Mohammed Rohaim, Lancaster University, United Kingdom

Reviewed by: A. Raj Kumar Patro, Kalinga Institute of Medical Sciences (KIMS), India

German Gustavo Gornalusse, University of Washington, United States

 *Correspondence: Qifa Liu liuqifa628@163.com 03 04 2025 2025 16 1518275 29 10 2024 10 03 2025 Copyright © 2025 Lin, Wu and Liu. 2025 Lin, Wu and Liu

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 Introduction

Cytomegalovirus (CMV) infection poses a significant threat to individuals undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), potentially resulting in substantial morbidity and mortality. This review summarized the epidemiology, clinical outcomes, and treatment patterns of CMV infection among allo-HSCT recipients in China.

 Methods

PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang and Chinese Biomedical Literature Database (CBM) were systematically searched from 2013 to March 2023. All analyses were performed using R 4.1.1 software with a random effects model.

 Results

Fifty-six studies, which included 13,882 patients, were reviewed. The pooled overall incidence of CMV infection was 49.99% [95% confidence interval (CI) 43.72–56.26%]. Among post allo-HSCT recipients with CMV infection, 32.03% (95% CI 22.93–41.12%) developed refractory CMV infection. The overall incidence of CMV disease was 13.30% (95% CI 8.99–19.66%). The pooled all-cause mortality rate was 29.25% (95% CI 17.96–40.55%) and the CMV-related mortality rate was 3.46% (95% CI 1.19–5.73%). Results demonstrate that management of CMV has mainly focused on pre-emptive therapy due to the treatment-limiting toxicity of anti-CMV agents. Additionally, CMV infection is continuing to occur after the discontinuation of prophylaxis, highlighting the unmet need for a more effective treatment without treatment-limiting toxicities.

 Conclusion

This review underscores the urgent need for improved therapeutic strategies to effectively manage cytomegalovirus infection in allo-HSCT recipients, particularly in light of the high incidence and associated morbidity, as well as the limitations of current treatment options.

 Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024513908, identifier: CRD42024513908.

 cytomegalovirus allogeneic hematopoietic stem cell transplantation epidemiology meta-analysis China section-at-acceptance Virology 1 Introduction

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for various hematological malignancies and disorders. Although this treatment modality offers the promise of hematopoietic system renewal, it poses unique challenges, particularly in terms of infectious complications, among which cytomegalovirus (CMV) emerges as a prominent adversary.

Globally, CMV infection is a well-documented threat in the context of allo-HSCT, influencing post-transplant outcomes (Camargo and Komanduri, 2017; Ljungman et al., 2017). Directly, CMV can initiate primary or reactive infection within recipients, leading to CMV viremia (Dziedzic et al., 2017). This uncontrolled viral replication may progress to CMV diseases, presenting as complications such as pneumonia, gastrointestinal complications and retinitis (Paris et al., 2009; Solano et al., 2013), contributing significantly to post-transplant morbidity and mortality (Mori and Kato, 2010; Giménez et al., 2019; Teira et al., 2016). Indirectly, CMV impedes the immune reconstitution process initiated by allo-HSCT, compromising the functionality of immune cells, particularly T cells. This weakened immune response heightens vulnerability to various opportunistic infections (Anderson-Smits et al., 2020; Nichols et al., 2002). Additionally, CMV is associated with an elevated risk of graft-vs.-host disease (GVHD), patient survival, non-relapse mortality and graft failure (Grigoleit et al., 2009; Teira et al., 2016; Fan et al., 2022; Boeckh and Geballe, 2011; Cantoni et al., 2010).

Since potent antivirals have been developed, CMV-related mortality and the incidence of CMV diseases have decreased (Gagelmann et al., 2018; Chen et al., 2018; Marty et al., 2019; Boeckh et al., 2015). Typically, management of CMV consists of prophylaxis or pre-emptive therapy. Unlike prophylactic therapy, which involves administering antiviral drugs to all at-risk patients regardless of their CMV status, pre-emptive therapy focuses on closely monitoring patients for early signs of CMV replication (e.g., through regular PCR testing) and initiating antiviral treatment only when a predefined viral load threshold is reached. Commonly employed antiviral agents for managing CMV worldwide encompass intravenous foscarnet, cidofovir, Ganciclovir and its valyl ester prodrug (valganciclovir), oral valganciclovir (Cho et al., 2019; Limaye et al., 2020). However, these drugs are associated with significant toxicity, including myelosuppression and nephrotoxicity (De Clercq and Li, 2016; George et al., 2010). Therefore, pre-emptive therapy is preferred to prophylaxis therapy in clinical practice to avoid the potential risk of drug-related adverse effects.

With CMV seroprevalence exceeding 90% in China's general population (Stem Cell Application Group, Chinese Society of Hematology, Chinese Medical Association, 2022), and haploidentical hematopoietic stem cell transplantation (haplo-HSCT) making up 60.1% of allo-HSCT cases in China (Xu et al., 2021), the likelihood of CMV infection following allo-HSCT in China is high, underlining the significant concern in this context. Therefore, this review aims to comprehensively summarize the epidemiology, clinical outcomes and treatment patterns of CMV infection among allo-HSCT recipients in China, including mainland China, Taiwan, Hong Kong and Macau.

 2 Methods

This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) (Page et al., 2021) extension for scoping reviews (Tricco et al., 2018). The protocol was registered on PROSPERO (registration number: CRD42024513908).

2.1 Data sources and literature search

An electronic database search of PubMed, EMBASE, the Cochrane Library, Web of Science, CNKI, Wanfang, and CBM was conducted in March 2023 to search for studies published over the past 10 years (from 2013 to 2023) using the keywords “cytomegalovirus”, “stem cell transplantation”, and “China”. We applied no restrictions on language or publication status. The search strategy is provided in Supplementary material.

 2.2 Study selection

Studies with standard of care that investigated allo-HSCT recipients in China were included. The following outcomes were of interest:

- Epidemiology outcomes including incidence of CMV infection, breakthrough infection which is defined as the development of an CMV infection that occurs during antiviral prophylaxis (Ljungman et al., 2019), and time to CMV infection onset;

- Clinical outcomes among patients with CMV infection including incidence of resistant CMV infection, refractory CMV infection, and recurrent CMV infection; time to CMV disease onset; and incidence of CMV disease; mortality rate; and incidence of other comorbidities with CMV infection among patients with CMV infection;

- Treatment patterns;

- Treatment-limiting toxicity.

We considered observational and interventional studies that reported in English or Chinese while excluding case reports, reviews, comments, and editorials. We excluded reports that not published in English or Chinese. Two reviewers independently screened articles for eligibility. Any disagreements were resolved through discussion with a third reviewer.

 2.3 Data extraction, synthesis, and analysis

Two reviewers independently extracted the following data from each study into a predefined data extraction form: study characteristics including first author's name, publication year, study design, geographic location of study, and sample size; participant characteristics including age, gender, type of transplant, and population description reported by the study, as well as outcomes. Any disagreements were resolved by discussion with a third reviewer.

Meta-analyses were performed using a random effects model with the meta package in R (version 4.1.1) when data was appropriate. For dichotomous outcomes, we extracted the reported rates and calculated as proportion and 95% confidence interval (95% CI) for each study, then pooled them by meta-analysis. When data was insufficient for meta-analysis, we described the outcomes narratively accompanied by tabulated and charted results. We used a raincloud plot to present the time to CMV infection, CMV disease onset and CMV viremia resolution when data was available from three or more studies. In a raincloud plot, each dot represents an individual study's effect estimate, the x-axis represents the measure of effects (i.e., time in days), and the box plot within each group summarizes the distribution of these estimates, with the central line indicating the median and the box showing the interquartile range. We used a pie chart to present the proportion of various agents in different therapeutic approaches. Heterogeneity of studies was assessed by the Cochrane Q-test with a significance level of 0.05 and the I2 statistic, where I2 ≥ 50% coupled with p < 0.05 from the Q-test was interpreted as evidence of substantial levels of heterogeneity. We conducted subgroup analyses to explore the potential sources of substantial heterogeneity. A funnel plot was performed for outcomes reported by 10 or more studies to assess publication bias.

Subgroup analyses were carried out on the incidence of CMV infection according to days after transplantation (within 100 days and within 200 days), prophylaxis therapy (breakthrough incidence, defined as the occurrence of CMV infection during prophylaxis therapy), patient age (adults and children), transplant type (human leukocyte antigen (HLA)-matched, HLA haploidentical, cord blood and unrelated-matched), and CMV serologic status prior to transplantation [donor-negative (D–)/recipient-negative (R–), donor-positive (D+)/recipient-positive (R+), D–/R+ and D+/R–].

 2.4 Quality assessment

The quality of included studies was assessed independently by two reviewers using Joanna Briggs Institute (JBI) critical appraisal tools for prevalence studies, case-control studies, cohort studies and randomized controlled trials (RCTs) (Barker et al., 2023; JBI, 2020). Any disagreements were resolved by discussion with a third reviewer.

 3 Results 3.1 Results of study selection

The database search returned 2,684 results and provided 1,472 unique citations after duplicates were removed. A further 1,232 articles were excluded at the title- and abstract-screening stage. Full papers were sought for the remaining 240 articles. Of these, 227 full papers were retrieved and assessed for eligibility according to the inclusion and exclusion criteria. The remaining 13 articles were not successfully retrieved due to unauthorized access. Finally, 56 studies that published in 57 reports (Cao et al., 2016a,b; Gao et al., 2013; Guo et al., 2016; Han et al., 2014; He et al., 2014; Huang et al., 2022, 2013; Jin et al., 2014; Li et al., 2015a,b, 2022a, 2020, 2013b; Ma et al., 2023b; Que et al., 2014; Shi et al., 2019; Si et al., 2013; Tan et al., 2020; Wan et al., 2017; Wang et al., 2015, 2017, 2019, 2021, 2013; Wei et al., 2022; Wu et al., 2019, 2017; Xiong et al., 2023; Xu et al., 2015; Xue et al., 2019a,b; Yin et al., 2020; Zhang et al., 2016, 2014; Zhao et al., 2020; Zhao and Sun, 2021; Zhu et al., 2020; Zou et al., 2016; Bao et al., 2016; Chen et al., 2022; Cheng et al., 2022; Ding et al., 2021; Li et al., 2021, 2022b, 2013a; Lin et al., 2017; Liu et al., 2015; Meng et al., 2020; Pei et al., 2022; Tong et al., 2013; Yan et al., 2020; Yeh et al., 2022; Yin et al., 2022; Zhang et al., 2021, 2022, 2017) met the full eligibility criteria and were included in the review. The study selection process is shown in Figure 1.

PRISMA flow chart of study selection.

 3.2 Characteristics and quality of included studies

We included a total of 56 studies with sample sizes ranging from 11 to 3,862 (Table 1). These studies comprised 25 cross-sectional studies, 24 cohort studies, five case-control studies, and two RCTs. The quality assessment results of the included studies are summarized in Supplementary Tables S1–S4.

Summary of characteristics of included studies.

Study ID (first author and publication year) Study design Institution Sample size Diagnosis (number of patients) Transplant type (number of patients) Age (years) CMV DNA in aqueous humor (copies/mL)
Bao 2016 Cohort The First Affiliated Hospital of Soochow University 685 AL: 495 NHL: 34 AA/PNH: 38 MDS/MPD: 68 CML: 47 Other: 3 Related HLA-identical sibling: 237 Related HLA-haploidentical: 261 Matched unrelated: 187 Median (range): 31 (2–58) NR
Cao 2016 Cross-sectional The First Affiliated Hospital of Zhengzhou University 134 AML: 43 CML: 53 ALL: 14 AA: 15 Others: 9 Haploid: 69 Full compatibility of siblings: 60 Non-related compatibility: 5 Peripheral hematopoietic stem cell transplantation: 121 Bone marrow combined with peripheral blood transplantation: 13 Median (range): 23 (5–50) Median: 3.95 × 103
Chen 2022 Case control National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital 359 AML: 237 ALL: 112 MAL: 10 Haploidentical-related donor: 195 MSD: 164 NR NR
Cheng 2022 Cohort National Cheng Kung University Hospital 11 ALL: 5 AML: 3 SAA: 2 HSTCL: 1 Matched sibling: 2 Matched unrelated: 5 Mismatched unrelated: 4 Median (range): Letermovir group: 16.1 (9.2–17.8) Control group: 13.9 (4.5–16.9) NR
Ding 2021 Cross-sectional The First Affiliated Hospital of Soochow University 160 NHL: 160 HLA-matched donor: 66 HLA-mismatched donor: 94 Median (range): 30 (5–59) NR
Gao 2013 Cross-sectional Anhui Medical University Provincial Hospital 107 AML: 41 ALL: 48 CML: 10 MDS: 4 NHL: 3 MPL: 1 Unrelated cord blood HSCT: 107 Median (range): 15 (2–46) NR
Guo 2016 Cross-sectional Beijing Military General Hospital 50 AML: 20 ALL: 12 AAA: 10 MDS: 6 Lymphoma: 2 Haplo-HSCT: 50 Mean (range): 23.8 (5–45) Range: 2.4 × 103 – 6.2 × 106
Han 2014 Cross-sectional First Affiliated Hospital of Anhui Medical University 82 CML: 31 AML: 20 AA: 15 ALL: 16 Allogeneic peripheral blood stem cell transplantation: 16 Allogeneic bone marrow transplantation: 13 Umbilical cord blood stem cell transplantation: 10 Allogeneic bone marrow + peripheral blood stem cell transplantation: 43 HLA fully matched: 73 HLA partially matched: 9 Age: no. of patients <14: 1 15–45: 58 ≥45: 23 NR
He 2014 Cross-sectional Zhongda Hospital Affiliated to Southeast University School of Medicine 108 AML: 24 ALL: 19 CML: 30 MDS: 20 LP: 4 SAA: 11 Completely matched unrelated donors: 26 Unrelated donor haploidentical: 17 Completely matched related donors: 44 Related donor haploidentical: 21 Age: no. of patients ≤ 18: 21 18–40: 43 ≥40: 44 NR
Huang 2013 Cross-sectional Peking University People's Hospital Institute of Hematology 327 NR Sibling fully matched transplants: 96 Haploidentical transplants from relatives: 216 Median (range): 29 (2–67) Median: 1.1 × 104
Huang 2022 Case control Guangdong Women and Children Medical Center Hematology and Oncology Department 257 Severe beta thalassemia: 257 HLA fully matched donors: 195 (106 related/89 unrelated) HLA partially matched donors: 65 (27 related/38 unrelated) Median (IQR): 6 (4–8) NR
Jin 2014 Cross-sectional The Affiliated Hospital of the Academy of Military Medical Sciences 115 AML: 31 ALL: 25 CML: 42 AA: 4 NHL: 5 MDS: 7 CLL: 1 Allogeneic peripheral blood HSCT recipients: 102 (non-myeloablative transplantation: 8 and haploidentical transplantation: 5) Allogeneic bone marrow HSCT recipients: 9 Allogeneic bone marrow + peripheral blood HSCT recipients: 4 Mean (range): 34 (17–58) Median: 4.0 × 103
Kong 2015 Cohort The Peking University People's Hospital 488 AML: 203 ALL: 158 MDS: 60 CML: 26 SAA: 26 FA: 1 Lymphoma: 9 Myeloma: 4 Myelofibrosis: 1 Matched sibling: 91 Mismatched family: 397 Median (range): 29 (2–61) NR
Li 2013a Cohort Chinese PLA General Hospital 141 AML: 57 ALL: 24 NHL: 16 MDS: 12 AA: 10 Chronic myelogenous leukemia: 19 Chronic myelomonocytic leukemia: 1 Chronic lymphocytic leukemia: 1 Other: 1 HLA-matched unrelated: 43 HLA-matched related: 79 HLA-mismatched related: 19 Median (range): 32 (10–56) Mean (95%CI): 1.53 × 103 (95% CI 1.39 × 103 – 1.81 × 103)
Li 2013b Cohort Affiliated Hospital of the Academy of Military Medical Sciences 63 AML: 15 ALL: 13 CML: 22 AA: 4 NHL: 4 MDS: 4 CLL: 1 Allogeneic peripheral blood HSCT recipients: 51 (including non-myeloablative transplantation: 4 and haploidentical transplantation: 2) Allogeneic bone marrow HSCT recipients: 7 Allogeneic bone marrow + peripheral blood HSCT recipients: 4 Umbilical cord blood HSCT recipient: 1 Mean (range): 33 (16–56) NR
Li 2015a Cross-sectional Anhui Medical University Provincial Hospital 100 CML: 5 ALL: 57 AML: 31 AMLL: 1 MDS: 4 Malignant lymphoma: 2 Unrelative cord blood transplantation: 100 Median (range): 13 (1.5–51) NR
Li 2015b Cohort Hematology Department, The Second Affiliated Hospital of Chongqing Medical University 30 AML: 12 CML: 7 CLL: 3 ALL: 3 SAA: 2 MDS transit to AML-M: 2 NHL: 1 Haplo-HSCT: 13 Unrelated HLA fully matched HSCT: 6 HLA-matched sibling HSCT: 11 (Among them: 10 cases involved peripheral blood stem cell transplantation, 5 cases involved a combination of peripheral blood stem cells and bone marrow transplantation, 15 cases involved a combination of peripheral blood stem cells, bone marrow, and umbilical cord blood mesenchymal stem cell transplantation) Median (range): 42 (12–60) NR
Li 2020 Cross-sectional Hematology Department, Shanghai First People's Hospital 411 AML: 14 ALL: 10 MDS: 5 NHL: 3 AA: 2 (34 cases with CMV pneumonia) Haploid: 230 HLA-matched related donors: 103 Unrelated donors: 78 Median (range): 32 (8–62) (34 cases of CMV pneumonia) Median (range): 1.45 × 105 (1.1 × 104 – 1.10 × 108)
Li 2021 Cohort Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital 84 AML: 58 ALL: 26 Haploid: 27 Haplotype match with a sibling: 37 Unrelated donor full match: 20 Median (range): 43 (18–74) NR
Li 2022a Cross-sectional Hematology Department, Peking University People's Hospital Institute 327 AML: 154 ALL:102 MDS: 39 Others: 32 Haploid: 241 Compatible siblings: 74 All unrelated donors are identical: 12 Median (range): FSC/GCV: 34 (14-64) CDV (first line): 32 (27–53) CDV (second line): 37 (16–57) Median (Q1, Q3): Co-reactivation:1.71 × 103 (1.14 × 103, 3.68 × 103); CMV reactivation:1.69 × 103(0.77 × 103, 3.50 × 103)
Li 2022b Case control Hematology Department, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine 408 AML: 146 CML: 40 ALL: 163 MDS: 37 AA: 22 Cord blood: 152 Peripheral blood stem cells: 92 Bone marrow: 48 Peripheral blood stem cells + bone marrow: 116 Age: no. of patients <40: 306 ≥40: 102 NR
Lin 2016 Cross-sectional Taichung Veterans General Hospital 82 AML: 39 ALL: 20 MDS: 1 CML: 3 AA: 9 Multiple myeloma: 2 Lymphoma: 8 Matched sibling donor: 27 Matched unrelated: 21 Mismatched unrelated: 29 Haploidentical: 5 Mean ± SD: 41.98 ± 14.57 NR
Ma 2023 Cohort Peking University Institute of Hematology 335 Single-drug therapy group: AML: 59 ALL: 31 MDS: 33 NHL: 10 AA: 14 Others: 9 Combination therapy group: AML: 24 ALL: 14 MDS: 10 NHL: 3 AA: 7 Others: 7 Haplo-HSCT: 335 Median (range): Single-drug therapy group: 29 (1–66) Combination therapy group: 32 (1-65) Median: Single-drug group: 5.4 × 103; Combination-drug group: 4.5 × 103
Meng 2020 Cross-sectional Peking University People's Hospital 3,862 NR Haploid: 3,862 NR NR
Pei 2022 Cohort Peking University People's Hospital 190 AML: 84 ALL: 73 MDS: 16 Others: 17 Haploid: 39 Median (range): 29 (2–66) NR
Que 2014 Cross-sectional Hematology and Oncology, Children's Hospital Affiliated to Chongqing Medical University 26 PID: 26 Sibling bone marrow transplant: 4 Cord blood transplant: 22 Median (range): 27 (7–77) months NR
Shi 2019 Cross-sectional Peking University People's Hospital 61 AML: 28 ALL: 25 AHL: 2 MDS: 6 Haploid: 39 Median (range): 30 (16–56) NR
Si 2013 Cohort Affiliated Bayi Children's Hospital, Beijing Military General Hospital 47 AML: 11 SAA: 8 High-risk ALL: 7 HPS: 6 DBA: 5 AMLL: 5 MDS: 2 NHL: 2 OF: 1 Haploid: 24 Sibling donor transplants: 16 Unrelative donor transplants: 7 Mean ± SD (range): 8.0 ± 6.4 (0.3–13.2) NR
Tan 2020 RCT Army Medical University Xinqiao Hospital Hematology Medical Center 69 NR HLA fully matched: 28 HLA haploidentical matched: 41 Median (range): 32 (4–59) Median (range): Ganciclovir group: 1.69 × 103 (5.66 × 102 – 1.83 × 103); Foscarnet group: 2.06 × 103 (4.46 × 102 – 2.09 × 104)
Tong 2013 Cohort Anhui Provincial Hospital (an affiliate of Anhui Medical University), Shandong Second Hospital (an affiliate of Shandong University School of Medicine) or Wuhu Yijishan Hospital (an affiliate of Wannan Medical College) 176 Hematological malignancies: 176 Umbilical cord blood transplantation from unrelated donors: 176 Mean (range): 20 (2.2–51) NR
Wan 2017 Cross-sectional Affiliated Hospital of Academy of Military Medical Sciences 41 SAA: 41 AHSCT: 41 Median (range): 26 (9–54) NR
Wang 2013 Cohort First Affiliated Hospital, Xi'an Jiaotong University School of Medicine 37 AML: 18 (among them: M1: 2, M2a: 11, M2b: 1, M4a: 1, M4b: 2, M5b: 1) ALL-L1: 4 ALL-L: 28 CML: 6 MPAL: 1 Allogeneic peripheral blood HSCT: 36 Bone marrow transplantation: 1 Unallogeneic HSCT: 16 Related HSCT: 21 HLA partially matched: 11 HLA fully matched transplantation: 26 Median (range): 29 (11–59) NR
Wang 2015 Cohort Tri-Service General Hospital Hematopoietic Stem Cell Transplantation Center 83 AML: 29 ALL: 17 MDS: 2 SAA: 32 CML-CP: 2 BP: 1 HSCT-HLA-matched (URD and MSD): 33 Haploid: 50 Median (range): 15 (2–48) NR
Wang 2017 Cross-sectional Pediatrics Department, Nanfang Hospital, Southern Medical University 310 NR Fully HLA-matched transplantation: 217 Half-matched transplantation: 93 Median (range): 5 (3–16) NR
Wang 2019 Cross-sectional Beijing Kyoto Children's Hospital Hematology and Oncology Department 167 NR Haplo-HSCT: 167 Mean ± SD: 6.96 ± 3.98 NR
Wang 2021 Cross-sectional Guangzhou First Municipal People's Hospital 270 SAA: 270 Haploid: 94 Compatible siblings: 108 Unrelated complete compatibility: 68 Median (range): 7 (1–14) NR
Wei 2022 Case control Children's Hospital of Fudan University Total: 143 No CMV infection: 112 CMV infection: 31 PID: 143 Cord blood: 143 Median (range): 33 (25–44) Median (Q1, Q3): 32.8 × 103 (18.3 × 103, 63.1 × 103)
Wu 2017 Cross-sectional The First Affiliated Hospital of PLA General Hospital 96 AML: 31 ALL: 23 MDS: 5 NHL: 9 SAA: 28 HLA-half-matched: 73 HLA-matched: 23 NR Median (range): 3.12 × 103 (5.10 × 102 – 6.30 × 105)
Wu 2019 Cross-sectional Guangdong Provincial People's Hospital 53 AML: 30 Lymphoma: 17 MDS: 1 MPN: 1 CML: 2 Myeloid sarcoma: 2 Unrelated: 17 Related: 36 Primary source of stem cells from peripheral blood: 45 Bone marrow: 5 Cord blood: 3 Median (range): 30 (16–54) NR
Xiong 2023 Cross-sectional First Affiliated Hospital of Chongqing Medical University 246 AML: 108 ALL: 60 AMLL: 6 MDS: 18 CML: 7 SAA: 28 MPN: 1 PNH: 1 Multiple myeloma: 7 Lymphoma: 10 Haplo-HSCT: 167 Sibling fully matched transplantation: 66 Unrelated donor transplantation: 13 (5 cases with HLA full match, 8 cases with 9/10 match) Median (range): 32 (14–65) NR
Xu 2015 Cohort Peking University People's Hospital Hematology Research Institute 28 AML: 10 ALL: 8 MDS: 4 CML: 3 AA: 2 CGD: 1 Haploid: 25 Haplotype match with a sibling: 2 Unrelated cord blood transplant: 1 Median (range): 29.5 (3–57) Median (range): 3.10 × 103 (0.49–46.50)
Xue 2019a Cohort North China University of Science and Technology Affiliated Hospital 60 AML: 24 ALL: 20 CML: 6 MDS: 10 HLA-matched: 22 HLA-mismatched: 38 NR NR
Xue 2019b Cohort Huabei University of Science and Technology Affiliated Hospital 40 AML: 12 ALL: 9 MDS: 5 CML: 3 AA: 11 HLA fully matched: 15 HLA partially matched: 25 NR NR
Yan 2020 Cross-sectional Peking University Institute of Hematology 1,466 AL or MDS: 1,466 Haplo-HSCT: 1,446 Median (range): 28 (1–66) Median (range): 1.56 × 105 (6.74 × 103 – 3.26 × 106)
Yeh 2022 Cross-sectional Kaohsiung Medical University Hospital 180 AML: 85 ALL: 48 CML: 10 SAA: 15 MDS: 15 NHL: 7 NR Median ± SD: 39.22 ± 11.76 NR
Yin 2020 Cohort Nanfang Hospital, Southern Medical University 17 AML: 10 NHL: 1 ALL: 3 MDS: 3 Haploid: 17 Median (range): 30 (16–56) Median (range): 2.662 × 103 (0.388 × 103 – 4.61 × 104)
Yin 2021 Cohort Nanfang Hospital, Southern Medical University 141 AML: FSC/GCV: 59, CDV: 5 ALL: FSC/GCV: 26, CDV: 2 MDS: FSC/GCV: 14, CDV: 2 NHL: FSC/GCV: 1, CDV: 0 MPAL: FSC/GCV: 1, CDV: 0 Haploid: 141 Median (range): 28 (5.5–58) Median (range): 8.65 × 103 (0.894 × 103 – 4.91 × 105)
Zhang 2014 Cross-sectional The 307th Hospital of the Chinese People's Liberation Army 80 AML: 30 CML: 9 ALL: 23 SAA: 11 MDS: 7 HLA-matched: 53 HLA-half-matched: 27 Median (range): 33 (8–58) NR
Zhang 2016 Cohort Third Military Medical University; Xinqiao Hospital; National Center for Hematological Diseases 165 AML: 71 ALL: 24 CML: 23 SAA: 2 Lymphoma/ lymphocytic leukemia: 13 AMLL: 5 MDS: 3 PNH: 1 MA: 1 Haploid: 99 HLA fully matched among relatives: 50 Unrelated full-matched: 16 Median (range): 26 (2–54) NR
Zhang 2017 Cohort Guangzhou First People's Hospital 12 SAA: 10 AML: 10 AHL: 1 HLA-related: 3 HLA-unrelated: 4 HLA-mismatched donors: 5 Mean ± SD (range): 26.6 ± 9 (18–49) NR
Zhang 2021 Cohort Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences 73 ALL: 11 AML: 39 MDS: 13 SAA: 4 Others: 6 Haplotype: 61 Compatible siblings: 12 Age: no. of patients ≤40: 38 >40: 35 Median (range): 1.73 × 103 (1.001 × 103 – 9.2278 × 104)
Zhang 2022 Cohort Guangzhou First People's Hospital 155 SAA: 155 Allogeneic HSCT (MSD): 71 Alternative donor (HID and URD): 84 Mean ± SD: 29.14 ± 9.12 9.77 × 103 ± 1.27 × 104
Zhao 2020 Cohort Peking University Institute of Hematology 122 AML: 47 ALL: 50 MDS: 15 CML: 10 Haplo-HSCT: 122 Median (range): 29 (1–63) NR
Zhao 2021 RCT Henan University of Science and Technology First Affiliated Hospital 78 NR NR Median (range): Total: 14 (8–27) months No CMV infection: 13.5 (7.3–26.0) months CMV infection: 15.0 (10.0–32.0) months NR
Zhu 2020 Case control Affiliated Children's Hospital of Soochow University 269 AL: 148 MDS/MPN: 18 Bone marrow failure diseases: 61 Immunodeficiency diseases: 26 Others: 16 [7 cases of MA; 1 case of NHL (IV); 1 case of chronic EB virus infection; 1 case of Crisp Oni syndrome; 3 cases of adrenoleukodystrophy; 2 cases of mucopolysaccharidosis type II; 1 case of pyruvate kinase deficiency] HLA-matched sibling donors: 33 HLA-haploidentical sibling donors: 116 Unrelated donors: 120 Median (range): 65 (33–115) months Median (range): RCI group:5.78 × 104 (2.1 × 104 – 1.5125 × 105); non-RCI group: 8.31 × 103 (2.845 × 103 – 2.315 × 104)
Zou 2016 Cohort Affiliated Hospital of the Academy of Military Medical Sciences 398 AML: 195 ALL: 141 MDS: 38 AA: 7 CML: 11 Others: 6 Unrelative allogeneic HSCT: 164 High-resolution matched sibling allogeneic HSCT: 165 Haplo-HSCT: 69 Median (range): 33 (10–64) NR

AA, aplastic anemia; AAA, acute aplastic anemia; AHL, acute hybrid leukemia; AHSCT, allogeneic hematopoietic stem cell transplantation; AL, acute leukemia; ALL, acute lymphoid leukemia; AML, acute myelocytic leukemia; AMLL, acute mixed-lineage leukemia; AP, accelerated phase; BAL, biphenotypic acute leukemia; BC, blast crisis; CDV, cidofovir; CGD, chronic granulomatous disease; CML, chronic myeloid leukemia; CML-CP, chronic myelogenous leukemia in chronic phase; CMV, cytomegalovirus; DBA, Diamond-Blackfan anemia; EB, Epstein-Barr; FA, Fanconi anemia; FSC, foscarnet; GCV, ganciclovir; Haplo-HSCT, haploidentical hematopoietic stem cell transplantation; HID, haploidentical donor; HLA, human leukocyte antigens; HPS, hemophagocytic syndrome; HSTCL, hepatosplenic T-cell lymphoma; IV, intravenous; MA, Mediterranean anemia; MDS, myelodysplastic syndrome; MPAL, mixed-phenotype acute leukemia; MPD, myeloproliferative disorders; MPL, mixed-phenotype leukemia; MPN, myeloproliferative neoplasm; NHL, non-Hodgkin lymphoma; NR, not reported; OF, osteopetrosis; PID, primary immunodeficiency diseases; PNH, paroxysmal nocturnal haemoglobinuria; SAA, severe aplastic anemia; SD, standard deviation; URD, unrelated donor.

 3.3 Epidemiology outcomes 3.3.1 Incidence of CMV infection and time to CMV infection onset

The meta-analysis of 47 studies conducted on 8,442 patients revealed that the incidence of CMV infection was 49.99% (95% CI 43.72–56.26%, Figure 2). The median time for CMV infection to develop after allo-HSCT was provided in 18 studies with 3,806 patients and found to be 37 days (Figure 3). Three studies with 151 patients reported the incidence of CMV breakthrough infection during foscarnet, ganciclovir and letermovir prophylactic therapy, and the pooled result was 7.29% (95% CI 3.09–11.48%, Supplementary Figure S1).

Forest plot of incidence of CMV infection in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients.

Raincloud plot for times to CMV infection, CMV breakthrough infection, CMV disease, CMV retinitis, and CMV pneumonia onset.

 3.3.2 Incidence of CMV infection based on transplantation type

Regarding transplant types, subgroup analyses revealed that the incidence of CMV infection was 70.82% (95% CI 58.29–83.35%) in unrelated matched transplantation, 69.08% (95% CI 61.50–76.66%) in haploidentical transplantation, 55.48% (95% CI 31.29–79.67%) in cord blood transplantation and 36.15% (95% CI 22.93–49.36%) in HLA-matched transplantation (Table 2, Supplementary Figures S2–S5).

Incidence of CMV infection based on days after transplantation, patient age, transplantation type, and donor and recipient CMV serologic status—subgroup analysis results.

Subgroup analysis Number of studies Sample size Pooled incidence (95% CI, I2)
Days after transplantation
Within 100 days 19 2654 47.46% (31.90–63.02%, 99%)
Within 200 days 4 520 67.50% (53.85–81.14%, 91%)
Age
Children 9 1,291 38.92% (26.14–52.49%, 95%)
Transplantation type
Unrelated matched 8 193 70.82% (58.29–83.35%, 73%)
Haploidentical 14 2,879 69.08% (61.50–76.66%, 94%)
Cord blood 5 438 55.48% (31.29–79.67%, 97%)
HLA matched 10 742 36.15% (22.93–49.36%, 93%)
Donor and recipient CMV serologic status
D– and R+ 6 313 57.64% (43.59–71.69%, 78%)
D– and R– 16 1061 47.99% (35.38–60.61%, 95%)
D+ and R+ 5 2183 45.86% (95% CI 32.77–58.95%, 97%)
D+ and R– 6 142 34.52% (12.27–56.77%, 88%)

CI, confidence interval; CMV, cytomegalovirus; HLA, human leukocyte antigens; “+” refers to positive CMV serologic status, “–” refers to negative CMV serologic status.

 3.3.3 Incidence of CMV infection based on donor and recipient CMV serologic status

The pooled incidence of CMV infection was 57.64% (95% CI 43.59–71.69%) based on the CMV serologic status of D–/R+, 47.99% (95% CI 35.38–60.61%) under the status of D–/R–, 45.86% (95% CI 32.77–58.95%) under the status of D+/R+ and 34.52% (95% CI 12.27–56.77%) under the status of D+/R– (Table 2, Supplementary Figures S6–S9).

 3.3.4 Incidence of cumulative CMV infection based on days after transplantation

The results showed that the incidence of cumulative CMV infection was 47.46% (95% CI 31.90–63.02%) within 100 days of transplantation and 67.50% (95% CI 53.85–81.14%) within 200 days (Table 2, Supplementary Figures S10, S11).

 3.3.5 Incidence of CMV infection based on patient age

Two studies (Li et al., 2015a, 2021) reported incidences of CMV infection among adult patients of 70.03 and 41.67%, respectively. In addition, the pooled results revealed that the incidence of CMV infection was 38.92% (95% CI 26.14–52.49%) among pediatric patients (Table 2, Supplementary Figure S12).

 3.4 Clinical outcomes among patients with CMV infection 3.4.1 Incidence of refractory, recurrent, and resistant CMV infection

After transplantation, 32.03% (95% CI 22.93–41.12%) of patients with CMV infection developed refractory CMV infection (five studies with 787 patients) and 15.42% (95% CI 7.76–30.63%) experienced CMV recurrence (12 studies with 697 patients, Supplementary Figures S13 and S14). Only one study on resistant CMV infection, which included 143 patients, was identified. Drug resistance rate seen in 0.7%.

 3.4.2 Incidence of CMV disease and time to CMV disease onset

A total of 18 studies including 1,362 patients reported the incidence of CMV disease among patients with CMV infection. The pooled incidence was 13.30% (95% CI 8.99–19.66%, Figure 4). The median CMV disease onset time was 51.5 days, based on six studies with 4,737 patients (Figure 3). Two studies (Ma et al., 2023b; Zhu et al., 2020) reported incidences of CMV disease among patients with refractory CMV infection of 3.4 and 3.3%, respectively.

Forest plot of incidence of CMV disease in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients with CMV infection.

Specifically, the incidence of CMV pneumonitis among patients with CMV infection pooled from 23 studies involving 7,434 patients was 5.96% (95% CI 4.44–8.00%, Supplementary Figure S15). The median time for CMV pneumonia onset was 90 days, based on five studies with 4,675 patients (Figure 3). Moreover, the pooled incidence was 13.48% for CMV cystitis, 7.12% for enteritis, 3.47% for retinitis, 0.59% for encephalitis, and 5% for hepatitis (He et al., 2014; Table 3, Supplementary Figures S16–S19). The median times to the onset of specific CMV diseases are shown in Table 4.

Incidence of CMV disease among patients with CMV infection in China.

CMV disease Number of studies Sample size Pooled incidence (95% CI, I2)
Pneumonitis 23 7434 5.96% (4.44–8.00%, 83%)
Cystitis 6 218 13.48% (4.88–22.08%, 77%)
Enteritis 8 518 7.12% (2.50–20.30%, 87%)
Retinitis 8 1,893 3.47% (1.60–5.33%, 81%)
Encephalitis 3 384 0.59% (0.00–1.35%, 0%)
Hepatitis 1 40 5.00%

CI, confidence interval; CMV, cytomegalovirus.

Median times to onset of CMV diseases after transplantation.

CMV disease Number of studies Sample size Median time to onset
Pneumonitis 5 4,675 90 days
Cystitis 1 165 36 days
Enteritis 2 115 and 3,862 41 and 46 days
Retinitis 5 5,662 161 days
Encephalitis 1 3,862 85 days
3.4.3 Mortality rate

The all-cause mortality rate was reported in nine studies with 710 patients and was found to be 29.25% (95% CI 17.96–40.55%, Supplementary Figure S20), whereas the CMV-related mortality rate was found to be 3.46% (95% CI 1.19–5.73%), based on 14 studies with 632 patients (Supplementary Figure S21).

 3.4.4 Incidence of comorbidities

Results pooled from four studies with 283 patients indicated that 64.20% (95% CI 31.22–97.18%) of patients with CMV infection experienced GVHD (Supplementary Figure S22). Another four studies with 248 patients reported an incidence of acute GVHD of 63.97% (95% CI 17.53–100.00%, Supplementary Figure S23). Two studies (Tong et al., 2013; Huang et al., 2022) reported incidences of chronic GVHD of 14.08% and 16.00%, and two studies (Yang et al., 2022; Huang et al., 2022) reported incidences of coexisting EB virus infection of 32.75 and 29.58%, respectively. The incidence of coexisting bacterial or fungal infection was 78.13%, as reported in one study (He et al., 2014) with 32 patients.

 3.4.5 Time to CMV viremia resolution

Eleven studies provided data on the time to CMV viremia resolution, and the median time was 14.5 days. The median time to refractory CMV viremia resolution, reported in three studies, was 20.5 days (Figure 5).

Raincloud plot for times to CMV and refractory CMV viremia resolution.

 3.4.6 Treatment patterns

Pre-emptive therapy was reported in 24 studies with 5,239 patients. Results indicated that ganciclovir was the most commonly used drug (42.19%), followed by foscarnet (20.54%) (Figure 6). For prophylaxis therapy, we identified the utilization of ganciclovir, ganciclovir in combination with acyclovir, foscarnet, foscarnet in combination with acyclovir, and letermovir.

Proportion of various drugs used in pre-emptive therapy.

 3.4.7 Treatment-limiting toxicity

We identified six studies that reported treatment-related adverse events associated with the use of cidofovir, foscarnet, ganciclovir, a combination of foscarnet and acyclovir, and a combination of ganciclovir and acyclovir. According to three studies, 34.90–41.20% of patients treated with ganciclovir experienced myelosuppression. Specifically, one study (He et al., 2014) reported that 34.90% patients experienced myelosuppression, one study (Tong et al., 2013) reported that 35.30% patients experienced neutrophilic leukopenia and one study (He et al., 2014) reported that 41.20% patients experienced granulocytopenia (grade III), and one study (He et al., 2014) reported that 11.40% patients experienced impaired kidney function.

 3.4.8 Publication bias

The results of the publication bias assessment for other analyses are presented in Supplementary Figures S24–32. Funnel plots indicated no obvious evidence of publication bias.

 4 Discussion

This review presents a comprehensive summary of the epidemiology, clinical outcomes, and treatment patterns of CMV infection among allo-HSCT recipients in China. Our findings indicate a substantial incidence of CMV infection in Chinese recipients of allo-HSCT (48.87%), which may vary according to the follow-up period, patient's age, transplantation type, and donor and recipient's CMV serologic status.

The incidence rates of CMV infection after allo-HSCT vary globally, ranging from 24.6 to 62.6% in North America, 28.9 to 63.9% in Europe, and 24.9 to 61.2% in other countries (Bergamasco et al., 2021; Cho et al., 2023). Our review found that the pooled incidence of CMV infection in Chinese recipients aligns with global trends and is at the higher end of values. This may be attributed to the presence of high risk factors in China, including the considerable prevalence of haplo-HSCT (60.1%) (Xu et al., 2021) and the high proportion of R+ individuals indicated by the high general incidence of CMV infection (>90%) in the Chinese population (Stem Cell Application Group, Chinese Society of Hematology, Chinese Medical Association, 2022). Consistent with the findings of the 2022 Chinese consensus (Stem Cell Application Group, Chinese Society of Hematology, Chinese Medical Association, 2022) and published evidence in Europe (Huntley et al., 2020; Solano et al., 2021) and North America (Huang et al., 2019; Webb et al., 2018) regarding risk factors of CMV infection after allo-HSCT, our review found that D–/R+ serostatus (57.64%), haplo-HSCT (69.08%) and unrelated-matched HSCT (70.82%) exhibited higher incidence rates than other serostatus conditions and transplant types. This underscores the necessity for tailored and culturally sensitive strategies to effectively mitigate risks associated with CMV. Notably, the high seroprevalence of CMV infection in China indicates that most patients have been exposed to the virus. Therefore, even with antiviral prophylaxis, reactivation of the virus may still occur, leading to breakthrough infections. Our results show that the rate of breakthrough infections is 7.29%. This highlights the need for regular monitoring of patients during prophylaxis, allowing for timely pre-emptive treatment upon detection of CMV reactivation to prevent progression to CMV disease or other complications.

In addition, the pooled incidence of CMV disease among recipients with CMV infection in China of 13.40% (95% CI 9.14–19.65%) is consistent with the estimates from other countries (2.9–15.7%) (Cho et al., 2023). In contrast to previous research findings, according to which CMV pneumonitis is the most frequent and common cause of death (Ljungman et al., 2019), our results indicate that the incidence of CMV pneumonitis (5.96%) was lower than that of CMV cystitis (13.48%) and CMV enteritis (6.62%). This unexpected result may stem from methodological variations across the included studies, which may indicate differences in study quality, diagnostic criteria and immunosuppressive treatment regimens across the included studies.

Moreover, our review found that 32.03% of recipients with CMV infection experienced refractory CMV, suggesting that some patients have inadequate responses to conventional treatment (Chemaly et al., 2019). Given that refractory CMV infection is recognized as an independent risk factor for CMV diseases and non-relapse mortality (Liu et al., 2015), concurrently increasing the risk of developing GVHD (Nho et al., 2023), the relatively high incidence may emphasize the need for heightened clinical attention after allo-HSCT. The high refractory CMV infections may be influenced by a variety of factors that can be broadly categorized into patient-related factors (e.g., immune status, serological status, transplant type), virus-related factors (e.g., High viral load), and drug-related factors (e.g., antiviral resistance, drug exposure). These factors interact in complex ways, making the management of refractory CMV infections particularly challenging. Our analysis of the included studies indicates that it is challenging to distinguish CMV infection rates due to the heterogeneity of the studies and the lack of detailed information on the specific drugs and regimens used. Thus, further large-scale prospective studies are warranted. Our review also obtained a rate of 15.42% for CMV recurrence after allo-HSCT among recipients with CMV infection. The refractory and/or recurrent CMV infection may be attributed to factors including mismatched donor transplants, T-cell depletion and CMV-seropositive recipients (Gagelmann et al., 2018; Liu et al., 2015; Almyroudis et al., 2007). This information indicates to clinicians the ongoing risk of refractory and/or recurrence CMV for recipients with CMV infection after allo-HSCT. Furthermore, the absence of resistance data suggests a potential lack of emphasis on resistance in clinical practice. Limited access to resistance detection methods may lead to an underestimation of the resistance incidence. It is crucial to accumulate more resistance data to enhance understanding of CMV resistance and to guide individualized treatment strategies.

The findings of this review indicate that ganciclovir, valganciclovir and foscarnet currently remain the most commonly used drugs in both prophylaxis and pre-emptive therapy in China. Despite their widespread use, these medications are associated with treatment-limiting toxicity. Our results reveal that a notable proportion of patients treated with ganciclovir and foscarnet experience myelosuppression (34.90–41.20%) and kidney function impairment (11.4%). The treatment related myelosuppression can directly impact the generation of cytotoxic T lymphocytes (CTL), leading to a delayed immune reconstitution associated with CTL (Martín-Gandul et al., 2014). Additionally, neutropenia may increase the risk of opportunistic infections and bleeding (Qi et al., 2022; Scott et al., 2008). Furthermore, foscarnet-induced nephrotoxicity can impact drug absorption and metabolism, potentially leading to conditions such as acute kidney injury and even uraemia in severe cases (Inose et al., 2022). The findings on treatment patterns highlight the unmet medical need in China for developing more effective and well-tolerated alternatives to fill the existing treatment gaps of CMV infection. With the availability of the novel drug letermovir, the treatment pattern in China is shifting from pre-emptive therapy toward prophylaxis therapy, although data on its efficacy and safety in the Chinese population remains limited (Stem Cell Application Group, Chinese Society of Hematology, Chinese Medical Association, 2022). A recent study published in 2023 supports the potential benefits of letermovir in reducing the incidence of CMV infection after haplo-HSCT without increasing the risks of aGVHD, non-relapse mortality and myelosuppression (Ma et al., 2023a). However, it is noteworthy that 17.6% of patients in the 2023 study still experienced CMV reactivation after discontinuation of letermovir, which may due to letermovir postponing CMV-specific immune reconstitution (Gabanti et al., 2022). It is worth mentioning that the recent approval of maribavir in China may offer a significant advancement in the treatment of post-transplant refractory CMV infections or diseases (PR Newswire, 2023). In the phase 3 RCT, maribavir exhibited greater efficacy than valganciclovir/ganciclovir, foscarnet, or cidofovir in CMV viremia resolution (55.7 vs. 23.9%) (Avery et al., 2022). This was coupled with a lower incidence of treatment-related acute kidney injury compared to foscarnet (1.7 vs. 19.1%) and reduced treatment-related neutropenia compared to valganciclovir/ganciclovir (1.7% vs. 25%) (Avery et al., 2022). The favorable efficacy and reduced treatment-related adverse events have the potential to address the current unmet treatment needs in this context (2023). Additionally, the development of CMV vaccines is progressing, with an mRNA-based vaccine demonstrating strong immune responses in laboratory studies (Fierro et al., 2024). A second-generation CMV vaccine candidate, T10-F10 (Yll-Pico et al., 2024), developed using a synthetic poxvirus platform, has shown high stability and immunogenicity in preclinical studies. CMV-specific T-cell therapies are also being explored as alternative strategies (Tang et al., 2024), with recent studies highlighting their potential in managing CMV infections. Future research should focus on optimizing these existing strategies and exploring new avenues.

Our study has several limitations. Despite efforts to include studies without restrictions on publication status, publication bias may still exist, as the included studies were identified using specific keywords in bibliographical databases. The exclusion of non-English and non-Chinese articles may lead to bias. This practice, known as language bias, can limit the generalizability of the findings and potentially skew the results by omitting key data from studies published in other languages. Moreover, the substantial heterogeneity observed across outcomes underscores the need for more homogeneous study designs and reporting standards in future research. Investigating the sources of this heterogeneity is essential to better understand the factors driving variations in CMV infection rates after allo-HSCT. These rates vary widely due to patient characteristics (e.g., CMV serostatus, age, underlying diseases), transplant type, immunosuppressive regimens, monitoring methods, geographic and demographic differences, post-transplant complications (e.g., GVHD), and variations in healthcare practices. The lack of a unified threshold for pre-emptive CMV treatment further contributes to this variability. Addressing these issues is critical to improving clinical management and advancing research in this field. In addition, we conducted a proportional meta-analysis, which restricted our ability to investigate the association between subgroup factors and the incidence of CMV infection. Future research could explore these potential confounders more comprehensively to provide a more detailed understanding of their impact on outcomes. Proportional meta-analysis synthesizes proportions from multiple studies into a pooled estimate, focusing on binary outcomes like CMV infection rates (Barker et al., 2021). However, this method limits the exploration of how subgroup factors, such as patient demographics, transplant characteristics, or treatment protocols, influence CMV infection rates. Therefore, further studies are warranted to investigate whether these subgroup factors contribute to the risk of CMV infection in recipients following allo-HSCT.

This review consolidates evidence on the epidemiology, clinical outcomes, and treatment patterns in recipients following allo-HSCT in China. Our results highlight a notable incidence of CMV infection in this population, with a portion of patients developing refractory CMV infection. Current anti-CMV therapies are limited and often associated with treatment-limiting toxicities, emphasizing the need for more effective and better-tolerated treatment options. Furthermore, the development of an effective CMV vaccine could further enhance the prevention and management of CMV infections in this high-risk population.

 Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

 Author contributions

RL: Conceptualization, Data curation, Formal analysis, Methodology, Supervision, Writing – original draft, Writing – review & editing. JW: Conceptualization, Data curation, Formal analysis, Methodology, Writing – original draft. QL: Conceptualization, Data curation, Formal analysis, Methodology, Supervision, Writing – original draft.

 Funding

The author(s) declare that financial support was received for the research and/or publication of this article. This study was funded by Takeda (China) International Trading Co., Ltd.

Scientific review of the manuscript was provided by Takeda Pharmaceutical Company Limited. Ms. Yang Zhang, Ms. Wenjie Zhang, and Dr. Sitong Dong from Shanghai Daotian Evidence-Based Technology Co., Ltd. provided assistance with the statistical methodology and analysis, and were funded by Takeda (China) International Trading Co., Ltd.

 Conflict of interest

JW is an employee of Takeda (China) International Trading Co., Ltd. RL has received speaker/consultancy fees and research fund from Takeda. QL has received speaker/consultancy fees and research fund from Takeda.

 Generative AI statement

The author(s) declare that no Gen AI was used in the creation of this manuscript.

 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.

 Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmicb.2025.1518275/full#supplementary-material

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