Cytomegalovirus (CMV) Infection and Disease Incidence and Risk Factors Across Diverse Hematopoietic Cell Transplantation (HCT) Platforms Using a Standardized Monitoring and Treatment Approach: A Comprehensive Evaluation From a Single Institution (2018)

CMV remains a major complication of allogeneic HCT, with over 40% of at risk recipients (donor (D) and/or recipient (R) seropositive) experiencing infection in the first 100 days post-HCT. At the NIH, all HCT recipients are monitored weekly from day 0-100 with blood CMV quantitative PCR (qPCR) with a uniform approach to preemptive therapy across HCT protocols. This offers a unique opportunity to comprehensively evaluate the cumulative incidence (CI) of and risk factors for post-HCT CMV infection and disease across different T cell manipulation approaches (posttransplantation cyclophosphamide (PTCy), proximal serotherapy, ex vivo T cell depletion (TCD), and calcineurin/mTOR inhibitor (CNI/mTORi) based) and different graft sources (marrow (BM), peripheral blood (PBSC), and cord blood (CB)). This is a retrospective study of 364 consecutive patients transplanted between Aug 10, 2011 and Feb 10, 2017. CMV infection was defined as 2 qPCRs between 3.08-4.11 log10 IU/mL in 1 week, 1 qPCR value >4.11 log10 IU/mL, or sufficient clinical suspicion for CMV disease to prompt therapy. Competing risks (CR) included death, relapse, and graft failure, with analyses including and not including systemic steroids for GVHD or engraftment syndrome as an additional CR. Recipient/donor/HCT characteristics are shown in Figure 1. Among at risk recipients, the 100 day CI of CMV infection was 46% (34% when systemic steroid use was included as a CR). The CI of CMV infection varied mainly by recipient CMV serostatus (Figure 2, P < .0001), with 100 day estimates of 2% (D/R −/−), 6% (+/−), 38% (−/+), and 40% (+/+). With regard to graft T cell manipulation, the 100 day CI of CMV infection, with (Figure 3, P = .029) and without steroids (p = NS) as a CR, respectively, was 25% and 42% (CNI/mTORi), 37% and 42% (serotherapy), 40% and 54% (PTCy), and 50% and 60% (TCD). CB was associated with 100 day CI of CMV infection of 64%, higher than BM at 39% and PBSCs at 30%, P = .002. There was a tendency toward lower 100 day CI of CMV infection for recipients of higher T cell doses when systemic steroid use was included as a CR, P = .07. Among CMV seropositive recipients, CMV therapy duration was longer with CMV seronegative donors (median 28 days) compared to CMV seropositive (median 20 days), P = .03. The median duration of CMV therapy was longer at 36 days for CB HCT, compared to PBSC (21 days) and BM (29 days), P = .03. CMV disease developed in 12 patients in the 100 days post HCT at a median of 27 days: 75% in the setting of GVHD, 83% in seropositive recipients, 75% involving gut, and occurring in .5% of PTCy, .4% of CNI/mTORi, .3% of serotherapy, and 0% of CB and TCD HCTs. In conclusion, CMV infection incidence varies based on recipient CMV serostatus, T cell manipulation strategy, and graft source, with longer treatment duration with seronegative donors and/or CB recipients. CMV disease rates before day 100 are similar across platforms and occur predominantly in the setting of GVHD.Figure 2Cumulative incidence of CMV infection in the first 100 days after HCT, by donor (D) and recipient (R) CMV serostatus.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Cumulative incidence of CMV infection in the first 100 days after HCT, by T cell manipulation strategy, with comparison using Gray's method of post-transplantation cyclophosphamide (PTCy), serotherapy (proximal ATG or alemtuzumab), ex vivo T cell depletion (TCD), and calcineurin inhibitor/mTOR inhibitor (CNI/mTOR)-based approaches.View Large Image Figure ViewerDownload Hi-res image Download (PPT)