A Modified Intensive Strategy to Prevent Cytomegalovirus Disease in Seropositive Umbilical Cord Blood Transplantation Recipients

Abstract

We previously demonstrated a lower rate of cytomegalovirus (CMV) reactivation and disease among seropositive umbilical cord blood transplantation (CBT) recipients receiving an intensive prophylaxis strategy consisting of ganciclovir on days -8 to -2 pretransplantation, high-dose valacyclovir post-transplantation, and twice-weekly serum CMV polymerase chain reaction testing. We hypothesized that a modified intensive strategy excluding pretransplantation ganciclovir would be similarly effective. We compared the risk of CMV reactivation, occurrence of CMV disease, and duration of anti-CMV therapy by day 100 post-CBT in patients receiving the modified intensive and intensive strategies. Forty patients received the modified intensive strategy, and 43 received the intensive strategy. There was no difference in the hazard for CMV reactivation (hazard ratio, 1.1; P = .77). No patients in the modified intensive cohort, but 2 patients in the intensive cohort, developed CMV disease (P = .53). There was no difference in the hazard for early (≤30 days post-CBT; P = .76) or high-level (>1000 IU/mL; P = .37) CMV reactivation. Patients in the modified intensive cohort had marginally higher CMV viral loads and percentage of days of CMV detection and treatment, although the contribution of pretransplantation ganciclovir to these differences is unclear. The overall percentage of treatment days was 32% in both cohorts after accounting for pretransplantation ganciclovir. In conclusion, exclusion of prophylactic ganciclovir before CBT did not impact the risk of CMV reactivation or disease, although CMV kinetics appeared to differ by prevention strategy. Best practices for CMV prevention will need further study as new prophylactic strategies become available.

Improved Survival after Cord Blood Transplantation: Single-Center Experience in Pediatric Patients Over a 2-Decade Period

“…Although Spees et al state that antiviral medications, such as ganciclovir and foscarnet, have not been proven effective in CMV prevention, we have shown decreased viral reactivation and, importantly, CMV disease in patients treated with an intensive prophylactic approach before transplantation [7]. These medications do have significant toxicities, however, and so more recently we have modified our preventive approach in adult patients [8] with plans to extend these modifications to the pediatric population. Newer antiviral medications, such as letermovir, appear promising and may further change the clinical approach to CMV prophylaxis [9].…”

New advances in the management of cytomegalovirus in allogeneic haemopoietic stem cell transplantation

“…Pre‐transplant recipient and/or donor CMV seropositivity is also associated with reduced survival and increased transplant‐related mortality compared with CMV seronegative pairs . Other well established and emerging risk factors for CMV include graft versus host disease (GVHD), corticosteroid use, umbilical cord transplants, haploidentical transplants with post‐transplant cyclophosphamide and T‐cell depleted grafts …”

“…Although valganciclovir, the oral prodrug of ganciclovir alleviates the requirement for intravenous therapy, dosing requires careful adjustment for renal function, as well as taking into consideration gut absorption, particularly in the presence of GVHD . Some institutes use high dose valaciclovir as prophylaxis against CMV in high‐risk seropositive umbilical cord transplants …”

“…3 Other well established and emerging risk factors for CMV include graft versus host disease (GVHD), corticosteroid use, umbilical cord transplants, haploidentical transplants with posttransplant cyclophosphamide and T-cell depleted grafts. [4][5][6] However, the increasing complexity and use of T-cell depleting conditioning regimens in HSCT have significantly impacted on the timing and kinetics of CMV viraemia in the post-transplant period. 1 CMV reactivation is no longer confined to the early post-HSCT period (<100 days) but may occur months later and with multiple recurrences despite adequate treatment.…”

“…22 Some institutes use high dose valaciclovir as prophylaxis against CMV in high-risk seropositive umbilical cord transplants. 6 Foscarnet is often used as a second line therapy following ganciclovir failure due to resistance, or adverse effects of ganciclovir, particularly myelotoxicity. 5 Inpatient admission is usually required due to the need for intravenous administration, the requirement for electrolyte replacement (particularly management of potassium, calcium and magnesium levels), the pre-/post-fluid required to prevent nephrotoxicity (occurring in up to 50% of patients), 23 and the need to monitor closely for adverse effects.…”