Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 2017 12 04() pii 10.1016/j.bbmt.2017.11.038
The optimal viral load threshold to initiate pre-emptive cytomegalovirus (CMV) therapy in hematopoietic cell transplant (HCT) recipients remains to be defined. In an effort to address this question we conducted a retrospective study of 174 allogeneic HCT recipients transplanted at a single center between August 2012 and April 2016. During this period, pre-emptive therapy started at the discretion of the treating clinician. 109 (63%) patients developed CMV viremia. Median time to reactivation was 17 (IQR, 7-30) days post-HCT. A peak viremia ≥150 IU/mL was strongly associated with a reduced probability of spontaneous clearance (RR, 95% CI: 0.16, 0.1-0.27), independent of established clinical risk factors including CMV donor serostatus, exposure to anti-thymocyte globulin and underlying lymphoid malignancy. The median time to clearance of viremia was significantly shorter in those who started therapy at CMV <350 IU/mL (19 days, 11-35) compared to those who started antiviral therapy at higher viremia thresholds (33 days, 21-42; p=0.02). The occurrence of treatment-associated cytopenias was frequent but similar in patients who started pre-emptive therapy at CMV <350 IU/mL and those who started at CMV >350 IU/mL (44 vs. 57%, p=0.42). Unresolved CMV viremia by treatment day 35 was associated with increased risk of therapeutic failure (32 vs 0%; p=0.001). Achieving eradication of CMV viremia by treatment day 35 was associated with a 74% reduction in one-year non-relapse mortality, NRM, (adjusted HR, 0.26; 95% CI, 0.1-0.8; p=0.02) whereas therapeutic failure was associated with a significant increase in the probability of one-year NRM (adjusted HR, 26; 95% CI, 8-87; p<0.0001). We conclude that among allogeneic HCT patients, a peak CMV viremia ≥150 IU/mL is associated with >80% reduction in the probability of spontaneous clearance independent of ATG administration, CMV donor serostatus, and lymphoid malignancy, and is a reasonable cutoff for pre-emptive therapy. Delaying initiation of therapy until CMV values ≥350 IU/mL is associated with more protracted CMV viremia, and unresolved viremia by treatment day 35 is associated with a significant increase in NRM.