Prevention of Cytomegalovirus Reactivation in Haploidentical Stem Cell Transplantation

Abstract

Cytomegalovirus (CMV) infection can increase the morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Because of a higher degree of immunosuppression, haploidentical transplant recipients may be at an increased risk of viral infections, particularly CMV. We retrospectively analyzed 86 haploidentical HCT recipients at our institution to determine whether a more intensified antiviral strategy would reduce the incidence of CMV reactivation compared with a traditional antiviral prophylaxis regimen. According to practice changes over time in antiviral prophylaxis at our institution, patients were divided into the following 3 groups: hybrid (n = 15), traditional (n = 26), and intermediate dose (n = 45). The hybrid group received valganciclovir from admission to day -2 followed by standard-dose valacyclovir. The traditional group received standard-dose valacyclovir starting on day -1. The intermediate-dose group received ganciclovir from admission through day -2, followed by intermediate-dose valacyclovir. The hybrid and intermediate-dose groups were combined into an intensified group for further analysis. We found the cumulative incidence (CI) of CMV reactivation within 100 days post-HCT was higher for patients receiving the traditional strategy compared with the hybrid and intermediate-dose strategy groups (81% versus 53% versus 71%, respectively; P = .08) and was significantly higher when the traditional group was compared against the intensified group (81% versus 67%, respectively; P = .032). Median time to CMV reactivation was also shorter in the traditional group versus the intensified group (31 versus 41 days, respectively). Moreover, the CI of CMV disease by day 100 was significantly worse for patients receiving the traditional prophylaxis strategy among the 3 groups (8% traditional versus 0% hybrid versus 0% intermediate dose; P = .032). Renal toxicity did not differ between the traditional and intensified group. In conclusion, an intensified approach to prevention of CMV reactivation was associated with lower incidence of CMV reactivation and less CMV disease without increased toxicity. Because the most benefit was observed in the intensified group, further studies are needed to assess which antiviral intervention is the most beneficial on lowering the rates of CMV viremia and disease.

Letermovir for primary and secondary cytomegalovirus prevention in allogeneic hematopoietic cell transplant recipients: Real‐world experience

“…Our institution reported rates of CMV viremia of 66.3% in a contemporary cohort of T‐cell–depleted HCT recipients.0 . Similarly, a 53%‐81% incidence of CMV viremia was reported in haploidentical allo‐HCT . In our study, clinically significant CMV was detected in only 1 of 30 patients (3%) who received a T‐cell–depleted or haploidentical allo‐HCT and took letermovir prophylaxis for a median of 122 days (range, 12‐270).…”

Haploidentical allogeneic hematopoietic stem cell transplantation increases the risk of cytomegalovirus infection in adult patients with acute leukemia

“…Bone marrow suppression limits the application of prophylactic ganciclovir in allo‐HSCT. Additionally, Hammerstrom et al demonstrated that an intensified valacyclovir approach significantly lowers the incidence of CMV infection as compared to that for standard‐dose valacyclovir. Recently, the efficacy of letermovir prophylaxis has been demonstrated; it significantly lowers the risk of clinically significant CMV infection compared with that of a placebo in allo‐HSCT recipients.…”

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

“…This approach resulted in significantly lower CMV reactivation and disease rates, as well as fewer days on anti-CMV therapy in patients with CMV reactivation. Similar strategies have been adopted for use in high-risk CBT recipients at other centers [1,9,10]. We subsequently instituted a modified intensive strategy that excluded pretransplantation ganciclovir given the potential for additional side effects, logistical barriers, and cost, with unclear benefit in the context of additional aspects of the prevention strategy.…”