Opportunistic Infections in Patients Receiving Post-Transplantation Cyclophosphamide: Impact of Haploidentical versus Unrelated Donor Allograft

Abstract

Post-transplant cyclophosphamide (PTCy) is an effective strategy for graft-versus-host disease (GVHD) prophylaxis and is the standard of care for haploidentical hematopoietic cell transplantation (HCT). It is increasingly used for matched and mismatched unrelated donor (MUD/MMUD) HCT, but infections remain a concern. The objective of this study was to evaluate the characteristics and risk factors for infections in haploidentical and unrelated donor HCT recipients treated with PTCy-based GVHD prophylaxis. This single-center retrospective study examined 354 consecutive adults undergoing HCT with PTCy-based GVHD prophylaxis (161 MUD/MMUD; 193 haploidentical) between 2015 and 2022. Opportunistic infections (OIs) including cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus (EBV), and invasive fungal disease (IFD) were assessed from day 0 through day +365. The one-year cumulative incidence function of OIs and non-relapse mortality were calculated using dates of relapse and repeat HCT as competing risks. Secondary analysis evaluated risk factors for OIs and NRM using univariate and multivariable Cox regression models. Haploidentical HCT recipients had an increased risk of OIs compared to unrelated donor allograft recipients (39% haploidentical vs. 25% MUD/MMUD; HR 1.70; 95% CI 1.16 - 2.49; p=0.006). On multivariable analysis, haploidentical donor (HR 1.50; 95% CI 1.01 - 2.23; p=0.046), prior HCT (HR 1.99; 95% CI 1.29 - 3.09; p=0.002), and diagnosis of acute GVHD (HR 1.47; 95% CI 1.02 - 2.14; p=0.041) were associated with an increased risk of OIs. Non-relapse mortality within the first year was not significantly different between the two groups (HR 1.11; 95% CI 0.64 - 1.93; p=0.70). Overall, haploidentical donor was a significant risk factor for OIs in patients receiving PTCy, although one-year NRM was not different between haploidentical and MUD/MMUD HCT recipients. CMV and adenovirus infections were significantly increased amongst haploidentical HCT recipients, while the incidence of EBV infection and IFD was similar between the groups. Our findings may have implications for infection monitoring and prophylaxis in the setting of PTCy, particularly in haploidentical HCT recipients.