Increased Risk of for Cytomegalovirus Reactivation after Allogeneic HSCT in T-Cell Depleted Patients
Authors: Molla Vinicius Campos , Azevedo Roberta , Ramos Jessica Fernandes , Ponciano Danilo Belchior , de Moraes Pedro Henrique Arruda , Da Fonseca Ana Rita , Seiwald Maria Cristina Nunez , Serpa Mariana , Ferreira Aliana Meneses , Szor Roberta Shcolnik , Leonel Rayana Bomfim , Xavier Erick Menezes , Rocha Vanderson , Tucunduva Luciana , Novis Yana , Nucci Marcio , Kallas Esper , Arrais Celso 
Published: February 2021

Background: Reactivation of Cytomegalovirus (CMV) is frequent after allogeneic hematopoietic stem cell transplantation (HSCT), occurring in approximately 70% of CMV seropositive patients. CMV reactivation is associated with higher non-relapse mortality (NRM) and worse overall survival (OS), but data in patients from Latin American countries, in which seroprevalence of CMV is higher, are lacking.
Objectives: We analyzed the potential risk factors for CMV reactivation and the possible impact of CMV reactivation or primo-infection on HSCT outcomes.
Patients and Methods: We performed an observational, retrospective study in 262 consecutive adult patients who underwent HSCT between April 2007 and April 2020 in two centers. The median follow-up was 30 months.
Results: The median age was 50 years (range 18 to 83), most patients (58%) were male, had acute leukemia (acute myeloid leukemia in 40%, and acute lymphoblastic leukemia in 19%), and received transplants from alternative donors (matched unrelated in 32% and haploidentical in 36%). Most transplants were from peripheral blood stem cells (73%), with reduced-intensity conditioning regimens (76%). T-cell depletion was performed in 71% (post-transplant cyclophosphamide in 40%, antithymocyte globulin - ATG in 29%, and alemtuzumab in 2%). Pre-HSCT CMV IgG serostatus of donor (D) and recipient (R) was as follows: D+/R+ in 64%, D-/R+ in 22%, D+/R- in 8%, and D-/R- in 6% only. No patient received primary CMV prophylaxis. CMV reactivations were observed in 164 patients (63%), and all received preemptive therapy at the discretion of the treating physician. The CI for CMV reactivation at 100 days (CICMV) was 74% in D-/R+, 65% in D+/R+, 30% in D+/R-, and 0% in D-/R-, p&lt;0.01, Figure 1). The CICMV was higher in patients receiving transplants with T-cell depletion (67% vs. 47% without T-cell depletion, p&lt;0.01), and in patients with acute graft-versus-host disease (GVHD, 91% vs. 53% without GVHD, p=0.01). By multivariate analyses, all three factors remained associated with the CMV reactivation: pre-HSCT positive CMV serostatus (Hazard Ratio - HR: 6.06; 95% Confidence Interval - 95%CI 2.76.-13.35), T-cell depletion (HR 1.65, 95%CI 1.20-2.27), and acute GVHD (HR 1.67, 95%CI 1.31-2.14). By multivariate analysis, there was no significant association between CMV reactivation and the risk of acute GVHD, chronic GVHD, mortality, relapse, or survival.
Conclusion: An increased frequency of CMV reactivation was observed in recipients with positive CMV serostatus, T-cell depletion, and acute GVHD. CMV reactivation had no significant impact on HSCT outcomes. Our findings may help to identify a group of patients who could benefit from closer monitoring and possibly primary prophylaxis with novel agents, such as letermovir.

Disclosures
No relevant conflicts of interest to declare.