Safety of Cytomegalovirus Prophylaxis on Engraftment in Pediatric Umbilical Cord Blood Transplant Following Reduced Intensity Conditioning

Abstract

Background Reduced intensity conditioning (RIC) transplant carries the advantage of decreased transplant related morbidity and mortality, however comes with an increased risk of viral infections, particularly cytomegalovirus (CMV) in the setting of serotherapy and umbilical cord blood (UCB) grafts. Given this, the use of prophylaxis is considered, though with hesitation given associated myelosuppression and nephrotoxicity. We report outcomes of CMV prophylaxis with ganciclovir and foscarnet on engraftment and viremia in the setting of RIC umbilical cord blood transplant (UCBT). Methods A retrospective chart review was conducted reviewing patients with non-malignant disease who underwent UCBT on an institutional protocol between 2016 - 2019. A RIC regimen was administered using alemtuzumab (Day -14), hydroyxurea (Day -14 to -5), fludarabine (Day -9 to -5), melphalan (split Day -4 & -3), and thiotepa (Day -2). ClinicalTrials.gov: NCT01962415. The patients were divided into 3 groups: patients who did not receive CMV prophylaxis (Group 1), patients who did (Group 2), and patients who received preemptive treatment prior to Day 0 due to CMV DNAemia (Group 3). CMV prophylaxis included ganciclovir 5 mg/kg/d (Day -10 to -2) followed by foscarnet 90 mg/kg daily (from Day +1) to reduce marrow suppression. Results Group 1 included 14 patients. Neutrophil engraftment occurred in all patients [median: 16 days; range: 11 – 33]. Platelet engraftment (> 50k) occurred at a median of 45.5 days (range: 33 – 79). Of the 14 patients, 1 patient received acyclovir as CMV prophylaxis while the remaining 13 received ganciclovir/foscarnet. 5 developed CMV viremia (max copies of 95,000 IU/mL); one of whom had graft rejection attributed to CMV. These patients were treated preemptively following detection of DNAemia. Group 2 included 6 patients. Neutrophil engraftment occurred in all patients [median: 15 days; range: 13 – 18]. Platelet engraftment occurred at a median of 32 days (range: 26 – 39). 5 patients developed CMV viremia (max copies of 3290 IU/mL). Similar to Group 1, these patients were also escalated to treatment doses of ganciclovir and switched to foscarnet and/or human CMV immune globulin (CytoGAM) with treatment failure. Group 3 included 2 patients who were found to have CMV DNAemia prior to Day 0 therefore received preemptive treatment. Neutrophil and platelet engraftment occurred at a median of 14 and 42 days, respectively. In all groups, no patient developed end-organ disease. Conclusion In our single-institution pediatric UCB transplant dataset, there is no suggestion that pre-engraftment exposure to CMV prophylaxis with ganciclovir and foscarnet impacted the kinetics of either neutrophil or platelet engraftment. Therefore, CMV prophylaxis in seropositive patients undergoing UCB transplant could be considered alongside preemptive therapy as an option for management of viral reactivation.