Cytomegalovirus-Tissue Invasive Disease in Allogeneic Hematopoietic Cell Transplant in the Setting of a Preemptive Strategy

Background: Monitoring of cytomegalovirus (CMV) DNA by PCR followed by preemptive treatment of CMV viremia (CMVV) is an acceptable preventive strategy to reduce the incidence of CMV tissue invasive disease (TID) after allogeneic hematopoietic cell transplant (HCT).  Despite proactive monitoring, some patients develop CMV TID leading to adverse outcomes. We seek to characterize risk factors associated with the development of CMV TID in HCT recipients who were monitored and treated preemptively.

Methods: We reviewed the charts of 256 adult HCT recipients, actively monitored for CMVV between January 1, 2009 and July 31, 2013.  Our center preemptively monitors allogeneic HCT recipients with weekly CMV DNA by PCR until Day + 100, and thereafter every 2 weeks in patients with GVHD.  Antiviral therapy was initiated within 1 day of identifying significant CMVV.  Patients with CMV TID occurring during preemptive monitoring were matched 1:1 by the underlying disease, year of transplant, and time of follow-up with controls that developed CMVV without TID.

Results: Of the 15 patients that developed CMV TID despite preemptive therapy, 10 (66.7%) occurred within the first 100 days following HCT. Median time from HCT to CMV TID was 62 days (range 25 -1137).  All cases were gastrointestinal CMV TID with 1 case of CMV-associated oral mucositis.  9/15 (60%) had concurrent CMVV at the time of CMV TID diagnosis, and 4/15 (26%) were preemptively being treated with antivirals for CMVV at the time of CMV TID diagnosis.  The mean viral load was 1,738.5 copies DNA/mL, range (0-9,699 copies DNA/mL).  6/15 (40%) had at least one prior episode of CMVV which had previously resolved.  When compared with controls there were no significant differences in age, type of HCT, time to CMV TID, conditioning therapy, donor matching, comorbidities, GVHD, level of initial CMVV, or CMV donor/recipient serological status.  No ganciclovir resistance was identified in patients with CMV TID.

Conclusions:  All cases of CMV TID were gastrointestinal disease and tended to occur early after HCT.  CMV TID developed in the majority without preceding viremia.  There were no risk factors that could specifically identify patients likely to develop CMV TID despite pre-emptive monitoring and treatment.  Gastrointestinal CMV TID remains an inherent complication of a CMV preemptive strategy.