Chronic graft-versus-host disease (cGvHD) limits the effectiveness of hematopoietic cell transplantation (HCT) and often leads to significant morbidity and non-relapse mortality. 1 We have previously shown that antibodies targeting Y-chromosome encoded proteins (HY antibodies) detected at 3-months post transplant in male HCT patients who receive grafts from a female donor (F→M) are associated with cGvHD development, non-relapse mortality (NRM), and decreased overall survival (OS). 2,3 However, it is not known if this marker can be applied to the general population. In this multi-center, retrospective cohort study, we measured HY antibody levels in 234 F→M HCT patients with either plasma or serum samples collected at both the 3-month and 1-year post-transplant time points and determined the multivariable-adjusted relationship between the presence of multiple HY antibodies (represented as HY score) and cGvHD development.We quantified antibodies against the five most informhaematologica 2019; 104:e314 LETTERS TO THE EDITOR Figure 1. Anti-HY antibody responses in female donor to male recipient (F→M) hematopoietic cell transplantation (HCT) recipients with and without chronic graft-versus-host disease (cGvHD). Comparison included 234 F→M samples taken three months post transplant (3M) and 185 samples taken one year post transplant (1Y). Intensity of the antibody response is color-coded as a multiple of each HY-seropositivity threshold. HY score represents the cumulative number of seropositive HY antigens. Seropositivity frequencies for each antibody are listed along the bottom border of each heat map. HY score frequency refers to the frequency of an HY score >1.