Transplantation and Cellular Therapy · Sep 6, 2026

Differential Impact of Graft-Versus-Host Disease Prophylaxis on Cytomegalovirus Infection and Survival Outcomes after Cord Blood Transplantation in the Era of Letermovir

By Kawamura S, Akahoshi Y, Nakasone H et al.

Although recent studies suggested an enhanced graft-versus-tumor (GVT) effect with cord blood transplantation (CBT), higher rates of engraftment failure, acute graft-versus-host disease (GVHD), and infections, including cytomegalovirus (CMV), contribute to increased nonrelapse mortality (NRM). Thus, further optimization of GVHD and infection prophylaxis strategies for CBT is warranted. This study evaluated the impact of GVHD prophylaxis with methotrexate (MTX) versus mycophenolate mofetil (MMF) after CBT on CMV infection and survival outcomes, considering the use of letermovir (LTV) prophylaxis. We studied 2849 CMV seropositive adult patients who underwent CBT. In the absence of LTV, 6-month clinically significant CMV infection (csCMVi) was significantly higher in patients receiving MTX than in those receiving MMF (64.7% versus 52.1%, P < .001), while a similar incidence of csCMVi was observed with LTV (28.2% versus 32.9%, P = .098). Multivariable analyses confirmed these findings. The risk of acute GVHD was lower in patients receiving MTX than in those receiving MMF, regardless of LTV use. NRM at 12 months was comparable between patients receiving MTX and MMF without LTV (19.1% versus 20.4%, P = .577). Importantly, LTV mitigated the disadvantage of MTX with respect to csCMVi, and patients receiving MTX with LTV exhibited a lower NRM than those receiving MMF with LTV (11.5% versus 17.8%, P = .003), a finding that remained significant in multivariable analysis. This study highlights the potential for further optimization of GVHD and infectious prophylaxis strategies in CBT, thereby reducing NRM while maintaining a potent GVT effect.

doi.org/10.1016/j.jtct.2026.09.007PubMed 42702302Interventions