The use of post-
transplantation cyclophosphamide (PTCy) for
graft-versus-host disease (GVHD) prophylaxis in recipients of haploidentical and fully matched
transplantations is on the increase. Published studies have reported an increased incidence of cytomegalovirus (CMV)
infection with the use of PTCy. Limited data exist on the incidence and outcomes of
infection with non-CMV herpesviruses (NCHV) in this setting. The aim of this study was to evaluate the cumulative incidence of NCHV
infections and the association of NCHV
infections with
transplantation-specific outcomes in recipients of
haploidentical transplantation with PTCy (HaploCy), matched sibling donor
transplantation with PTCy (SibCy), and matched sibling donor
transplantation with
calcineurin inhibitor-based prophylaxis (SibCNI). We hypothesized that, like CMV
infection, HaploCy recipients of also will have a higher risk of NCHV
infections. Using the Center for International Blood and Marrow
Transplantation Research database, we analyzed 2765 patients (HaploCy, n = 757; SibCNI, n = 1605; SibCy, n = 403) who had undergone their first
hematopoietic stem cell transplantation (HCT) between 2012 and 2017 for
acute myelogenous leukemia,
acute lymphoblastic leukemia, or
myelodysplastic syndrome. The cumulative incidence of NCHV at 6 months post-NCT was 13.9% (99% confidence interval], 10.8% to 17.3%) in the HaploCy group, 10.7% (99% CI, 7.1% to 15%) in the SibCy group, and 5.7% (99% CI, 4.3% to 7.3%) in the Sib CNI group (P < .001). This was due primarily to a higher frequency of human herpesvirus 6
viremia reported in patients receiving PTCy. The incidence of Epstein-Barr
viremia was low in all groups, and no cases of post-
transplantation lymphoproliferative disorder were seen in either PTCy group. The incidence of NCHV organ disease was low in all 3 cohorts. The development of NCHV
infection was associated with increased treatment-related mortality, particularly in the HaploCy group. There was no association with the development of GVHD, relapse, or disease-free survival. Patients in PTCy cohorts who did not develop NCHV
infection had lower rates of cGVHD. This study demonstrates that the use of PTCy is associated with an increased risk of NCHV
infection. The development of NCHV
infection was associated with increased nonrelapse mortality, especially in the HaploCy group. Prospective trials should consider viral surveillance strategies in conjunction with assessment of immune reconstitution for a better understanding of the clinical relevance of viral reactivation in different HCT settings.