Prophylactic Pretransplant Ganciclovir to Reduce Cytomegalovirus Infection after Hematopoietic Stem Cell Transplantation

Introduction Cytomegalovirus (CMV) reactivation remains a serious complication after allogeneic hematopoietic stem cell transplantation (HCT) occurring in 35-55% of HCT recipients. CMV reactivation can lead to adverse outcomes including end-organ damage and graft failure. Objective To reduce the incidence of CMV reactivation and disease by using prophylactic ganciclovir pretransplant. Methods We conducted a retrospective analysis of all recipient or donor CMV seropositive patients who received their first allogeneic HCT between 2012 and 2017. Ganciclovir was administered pretransplant (5 mg/kg twice daily IV from day −8 to day −2). Patients received valacyclovir or acyclovir starting day 0 until one-year posttransplant. Patients were monitored weekly with serum CMV PCR through Day 100 posttransplant. CMV reactivation was defined as a CMV viral load of more than 135 IU/ml, and was treated with preemptive therapy. All patients received GVHD prophylaxis with calcineurin inhibitor. Results Seventy-nine consecutive patients were treated. The median age was 58 years (range 20 to 72). The most common diagnoses were acute myeloid leukemia (49%) and acute lymphocytic leukemia (14%). Graft sources were matched related donor (30%), matched unrelated donor (35%), haploidentical (5%) and cord blood (29%). 43 patients (55%) received myeloablative conditioning. 36 patients (45%) received fludarabine based reduced intensity/nonmyeloablative conditioning. 24 patients (30%) had CMV reactivation with median time of reactivation of 47 days posttransplant (range 27 to 229). 22 out of the 24 (88%) patients required treatment for CMV reactivation with a median treatment duration of 37 days (range 14 to 315) and were treated with ganciclovir or foscarnet. The cumulative incidence of CMV reactivation at day 100 posttransplant was 27% with a 95% CI (18%-37%) depicted in Figure 1. There were no patients with biopsy proven CMV disease or deaths attributed to CMV reactivation or disease. The median time-to neutrophil recovery (≥500 K/ul) was 18 days and the median time to platelet recovery (≥20,000 K/ul) was 19 days. The incidence of acute GVHD Grades II-IV was 25 %. The incidence of significant kidney injury (Creatinine >2.5 mg/dL) was 2.4%. Conclusions The incidence of CMV reactivation, in this high-risk patient population, by day 100 of 27% with pretransplant ganciclovir may be improved compared to historical controls of 35-55%. The use of pretransplant ganciclovir was associated with no CMV disease and was safe, with low incidence of kidney damage. These data suggest that pretransplant ganciclovir with preemptive therapy for viral reactivation should be considered regardless of graft source. Future prospective randomized trials are needed to evaluate strategies for CMV prophylactic regimens.