Female-to-male allogeneic transplantation affects outcomes differently according to the type of haplo-transplantation

• Published in: Cytotherapy (Oxford, England) England), 2024-10
• Main Authors: Tamaki, Masaharu, Kawamura, Shunto, Takano, Kosuke, Nakamae, Hirohisa, Doki, Noriko, Ohigashi, Hiroyuki, Maruyama, Yumiko, Ota, Shuichi, Hiramoto, Nobuhiro, Eto, Tetsuya, Yoshihara, Satoshi, Matsuoka, Ken-ichi, Masuko, Masayoshi, Onizuka, Makoto, Kanda, Yoshinobu, Fukuda, Takahiro, Atsuta, Yoshiko, Yanagisawa, Ryu, Yakushijin, Kimikazu, Nakasone, Hideki
• Format: Article
• Language: English
• ISSN: 1465-3249; 1477-2566; 1477-2566
• DOI: 10.1016/j.jcyt.2024.09.007

Allogeneic hematopoietic stem cell transplantation from a female donor to a male recipient (female-to-male allo-HCT) is a well-established risk factor for chronic graft-versus-host disease (GVHD) and non-relapse mortality (NRM). The inferior outcomes of female-to-male allo-HCT are considered to be due to allo-immunity against H-Y antigens. However, the influence of minor histocompatibility antigens in haplo-identical allo-HCT remains to be elucidated. We investigated the impact of female-to-male allo-HCT according to the haplo-HCT subtype. In the post-transplant cyclophosphamide (PTCY) cohort (n = 660), a female-to-male sex-mismatch was significantly associated with a decreased risk of relapse (HR: 0.70 [95% CI: 0.49–0.99], P = 0.045), but not with overall survival (OS) or NRM (HR: OS 0.89 [95% CI: 0.68–1.16], P = 0.40; NRM 0.98 [95% CI: 0.68–1.41], P = 0.90). On the other hand, in the non-PTCY cohort (n = 219), a female-to-male sex-mismatch was associated with inferior risks of OS and NRM, but was not associated with relapse. These results suggested that the survival impact of the haplo-HCT subtype differed according to the presence of a sex-mismatch. PTCY might be feasible for overcoming the inferiority of female-to-male allo-HCT and might preserve a GVL effect against H-Y antigens.