Clinically significant cytomegalovirus infection (csCMVi) after matched related donor allogeneic HSCT using post-transplant cyclophosphamide: A systematic review and meta-analysis.

Abstract

Abstract Background: Post-transplant cyclophosphamide (PTCy) is increasingly used as graft-versus-host disease (GVHD) prophylaxis in matched related donor (MRD) allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the risk of clinically significant cytomegalovirus infection (csCMVi) including reactivation and end-organ disease is poorly defined in this population. We conducted a systematic review and meta-analysis to assess the burden of csCMVi in MRD transplants receiving PTCy.Methods: A systematic review was conducted according to PRISMA guidelines. PubMed, Embase, Scopus, and Cochrane CENTRAL were searched for studies of csCMVi incidence in adult patients with hematologic malignancies undergoing matched donor allo-HSCT with PTCy-based GVHD prophylaxis. Studies not stratifying data for MRD recipients were excluded. A proportion meta-analysis was conducted using a random-effects model with Freeman-Tukey double arcsine transformation. Between-study heterogeneity was assessed using the I² statistic, and pooled estimates were calculated using the DerSimonian-Laird method. All analyses were conducted using R (version 4.5.0, R Core Team).Results: Six studies encompassing 964 MRD allo-HSCT recipients were included. The median age across studies ranged from 46 to 60 years, with a pooled female proportion of 41.3% (95% CI: 36.2–46.4%; I² = 55.1%). Most patients were transplanted for myeloid malignancies (pooled estimate: 79.5%; 95% CI: 69.3–89.7%), with lymphoid malignancies accounting for 17% (95% CI: 8.6–25.5%). CMV serostatus was predominantly donor-positive/recipient-positive (D+/R+), followed by D−/R+, D+/R−, and D−/R−. None of the studies reported use of anti-CMV prophylaxis. The pooled CMV reactivation incidence was 27.3% (95% CI: 12.3–42.3%), with significant heterogeneity (I² = 97.2%). Individual study-level incidence ranged from 4% (Mehta RS, 2022) to 37% (Goldsmith SR, 2021). Forest plot analysis demonstrated considerable between-study heterogeneity. All analyses were conducted using R (v4.5.0), applying the DerSimonian-Laird method for pooled estimates.Conclusion: Despite the use of PTCy in MRD allo-HSCT, clinically significant CMV infection remains a frequent and clinically relevant complication, with pooled incidence approaching 30%. The marked heterogeneity underscores the need for consistent antiviral prophylaxis and stratified CMV risk assessment.The consistent absence of anti-CMV prophylaxis such as Letermovir underscores the need for standardized prevention protocols. Notably, data on CMV incidence in patients receiving prophylaxis are lacking, warranting further studies.