Analysis of cytomegalovirus (CMV) infections in the first 180 days in adult sero-positive cord blood transplantation (CBT) recipients reveals high infection rates and treatment burden

Background: CMV infection can increase morbidity & mortality after CBT. We investigated the incidence & treatment burden of CMV infections in the 1st 180 days post-CBT. Methods: Adult CMV seropositive CBT recipients transplanted 3/2013-4/2017 were analyzed. Pts received Cy 50/Flu 150/Thio 5-10/TBI 400 cGy + CSA/MMF (no ATG) + ganciclovir prophylaxis 5 mg/kg IV daily days -7 to -2 & then standard dose acyclovir. Viremia was monitored by Roche qPCR (lower limit 137 IU/ml) 2×/week from =day +14. Treatment was usually initiated at 1st-2nd qPCR positivity. Maintenance versus induction foscarnet, ganciclovir or valganciclovir dosing were based on viremia level & assessment of severe infection versus drug toxicity risks. Response was 3 consecutive negative qPCRs & no disease. Results: 55 pts [median 52 yrs (range 23-66), 42 acute leukemias, 7 MDS/MPD, 6 lymphomas] received double unit grafts [median HLA-match 5/8 (range 2-7/8)]. 98% engrafted (1 graft failure unrelated to CMV) & 78% had grade II-IV aGVHD by day 100 (median onset 34 days, range 15- 91). 46 pts developed CMV infection. Details of infection days 1-180 & disease are shown (Figures 1 and 2). All 1st infections occurred by day 100: cumulative incidence 84% (95%CI70-91), median onset 35 days (range 5-74), median 1st detection viral load <137 IU/ml (range < 137-245), & median 1st 100 days peak viremia 404 IU/ml (range < 137-146,304). Median detection to therapy time was 3 days (range 0-39). Therapy of 1st infection was induction (30/46, 65%) or only maintenance (16/46, 35%). In the 1st 100 days, 27/46 (59%) pts cleared their 1st infection, 14/46 (30%) did not, & 5 (11%) died with CMV causing or contributing to all 5 early deaths. Of the 27 pts who cleared, 14 did not reactivate again by day 100, 13 did, & short duration of initial therapy was associated with a high risk of rapid 2nd reactivation. Only 4/41 pts remained cleared & off therapy by day 100. During days 101- 180, one pt died of GVHD with CMV, & the majority of remaining pts with early CMV had recurrent infection &/or remained on therapy. The median total therapy time was 58 days (range 4-92) in days 1-100, & 57 days (range 0-80) in days 101-180. Therapy toxicities were significant & frequently required drug discontinuation or therapy switches. Overall, at day 180, all 9/9 (100%) without infection survived versus 40/46 (87%) of pts with infection. Conclusions: CMV infection is frequent in adult seropositive CBT recipients. While early monitoring & pre-emptive therapy is effective in most pts, 6/55 (11%) developed disease in this analysis. Therapy burden is substantial in the 1st 6 months. Moreover, while optimal therapy intensity & duration is unknown, short therapy duration early post-CBT risks rapid CMV recurrence. This data supports investigation of new approaches to CMV prophylaxis, formal study of standardized dosing guidelines, less toxic therapies, & new assays to predict initial & recurrent infection risks.