[The impact of collateral CMV-seropositive and CMV-seronegative donors on the outcomes of allogeneic hematopoietic stem cell transplantation].

Abstract

Objective: To investigate the impact of collateral cytomegalovirus (CMV) -positive versus CMV-negative donors on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Method: This retrospective cohort study analyzed CMV-related events and survival outcomes in allo-HSCT recipients with CMV seropositive who received grafts from CMV-negative (CMV-negative donor group) or collateral CMV-positive (collateral CMV-positive donor group) haploidentical donors at Peking University People's Hospital from January 2017 to March 2025. Results: A total of 126 patients were enrolled, including 16 CMV-negative and 58 collateral CMV-positive donors before the availability of letermovir, and 27 CMV-negative and 25 collateral CMV-positive donors after the availability of letermovir. With a median follow-up of 1 091 (660, 1 536) days, before the availability of letermovir in China, the CMV-negative donor group had a significantly higher incidence of refractory CMV viremia (87.5% vs 50.0%, P=0.007) and a longer median duration of first CMV viremia [29 (95% CI: 25-33) vs 17 (95% CI: 15-19) days, P=0.004] than the collateral CMV-positive donor group. The use of letermovir significantly delayed the onset of first post-transplant CMV viremia in both groups: from day 37 (95% CI: 31-43) to day 140 (95%CI: 136-144) in the CMV-negative donor group (P<0.001) and from day 36 (95% CI: 33-39) to day 111 (95% CI: 76-146) in the collateral CMV-positive donor group (P=0.013). With letermovir prophylaxis, the difference in the median duration of the first CMV viremia between the CMV-negative and collateral CMV-positive donor groups was no longer significant [18 (95% CI: 17-19) vs 12 (95%CI: 0-25) days, P=0.313]. Letermovir reduced the incidence of refractory CMV viremia in the CMV-negative donor group (40.7% vs 87.5%, P=0.003), but the incidence remained higher than that in the collateral CMV-positive donor group (40.7% vs 12.0%, P=0.020). Regardless of letermovir use, there were no statistically significant differences in the 3-year overall survival, non-relapse mortality, or cumulative relapse rate between the CMV-negative and collateral CMV-positive donor groups (all P>0.05). Multivariate analysis showed that CMV disease was an independent risk factor for overall survival (HR=3.0, 95%CI: 1.3-7.3, P=0.014) and non-relapse mortality (HR=3.1, 95%CI: 1.1-8.8, P=0.035). Refractory CMV viremia was an independent risk factor for CMV disease (HR=12.0, 95%CI: 2.9-50.7, P=0.001). Logistic regression analysis showed that having a CMV-negative donor status without letermovir prophylaxis was an independent risk factor for refractory CMV viremia (P=0.005) . Conclusion: CMV-negative donors increase the risk of CMV-related events in recipients. Although letermovir prophylaxis mitigates this risk, the incidence of refractory CMV viremia remains higher in the CMV-negative donor group than in the collateral CMV-positive donor group, whereas the overall survival outcomes are comparable between the two donor sources.