Cytomegalovirus (CMV) management in allogeneic hematopoietic cell transplantation: Pre‐transplant predictors of survival, reactivation, and spontaneous clearance

Abstract Background Cytomegalovirus (CMV) reactivation is a frequent complication after allogeneic hematopoietic cell transplant (alloHCT). Method We analyzed 159 alloHCT recipients with 4409 quantitative CMV viral loads to determine pre‐transplant predictors of CMV reactivation, clinically significant CMV infection (cs‐CMVi, defined as CMV viral load >1000 IU/mL), CMV disease, kinetics of spontaneous clearance of CMV, and survival using a standardized pre‐emptive therapy approach to identify at‐risk groups to target prevention strategies. Results Cs‐CMVi was most common in D−/R+ unrelated donor transplants (URD). Spontaneous CMV clearance occurred in 26% of patients who reached a viral load of 56‐137 IU/mL, 6% at 138‐250 IU/mL and in one patient >250 IU/mL. Median time between the first CMV reactivation (>56 IU/mL) and a viral load >250 IU/mL was 13 days, whereas the time from the first viral load >250 IU/mL to reach a vial load >1000 IU/mL was 4 days. Cs‐CMVi was associated with a significant increase in non‐relapse mortality (NRM) on multivariate analysis. Conclusions Overall, this study indicates that D−/R+ URD recipients are at high‐risk for cs‐CMVi‐ and CMV‐related mortality, and are potential candidates for targeted CMV prophylaxis. Spontaneous clearance of CMV beyond a viral load of 250 IU/mL is uncommon, suggesting that this could be used as an appropriate threshold to initiate pre‐emptive therapy.