Increased Risk of for Cytomegalovirus Reactivation after Allogeneic HSCT in T-Cell Depleted Patients

Molla, Vinicius

Oral and Poster Abstracts
721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Poster III

Vinicius Campos Molla, MD^1,2^*, Roberta Azevedo²^*, Jessica Fernandes Ramos, MD, PhD^2,3^*, Danilo Belchior Ponciano^1,2^*, Pedro Henrique Arruda de Moraes, MD^1,2^*, Ana Rita Da Fonseca, MD^1,2^*, Maria Cristina Nunez Seiwald, MD^1,2^*, Mariana Serpa, MD²^*, Aliana Meneses Ferreira, MD^2,3, Roberta Shcolnik Szor, MD^2,3^*, Rayana Bomfim Leonel, MD^1,2^*, Erick Menezes Xavier, MD²^*, Vanderson Rocha, MD, PhD^2,3,4^*, Luciana Tucunduva, MD²^*, Yana Novis, MD²^*, Marcio Nucci, MD, PhD⁵, Esper Kallas, MD, PhD^2,3^* and Celso Arrais, MD, PhD^2,6^*

¹Universidade Federal de São Paulo, São Paulo, Brazil
²Hospital Sírio Libanês, São Paulo, Brazil
³Universidade de São Paulo, São Paulo, Brazil
⁴Department of Clinical Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
⁵Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil
⁶Division of Hematology, Universidade Federal de São Paulo, São Paulo, Brazil

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<0.01, Figure 1). The CICMV was higher in patients receiving transplants with T-cell depletion (67% vs. 47% without T-cell depletion, p<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.

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3293 Increased Risk of for Cytomegalovirus Reactivation after Allogeneic HSCT in T-Cell Depleted Patients