Differential impact of GVHD prophylaxis on CMV infection and survival outcomes after cord blood transplantation in the era of letermovir.

Authors

Shunto Kawamura, Yu Akahoshi, Hideki Nakasone, Naoyuki Uchida, Makoto Onizuka, Keisuke Kataoka, Koji Kato, Toshiro Kawakita, Mamiko Sakata-Yanagimoto, Masashi Sawa, Masatsugu Tanaka, Tomomi Toubai, Noriko Doki, Tetsuya Nishida, Yuta Hasegawa, Takeshi Maeda, Toshihiro Matsui, Hiroyuki Muranushi, Shingo Yano, Atsushi Wake, Marie Ohbiki, Yoshinobu Kanda, Yoshiko Atsuta, Junya Kanda, Kimikazu Yakushijin

Published in

Transplantation and cellular therapy. Sep 06, 2026. Epub Sep 06, 2026.

Abstract

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 csCMVi was significantly higher in patients receiving MTX than in those receiving MMF (64.7% vs. 52.1%, P < 0.001), while a similar incidence of csCMVi was observed with LTV (28.2% vs. 32.9%, P = 0.098). 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% vs. 20.4%, P = 0.577). 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% vs. 17.8%, P = 0.003), 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.

PMID:
42702302
Bibliographic data and abstract were imported from PubMed on 07 Sep 2026.

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