TY - JOUR
T1 - Human Cytomegalovirus-Specific T-Cell Reconstitution and Late-Onset Cytomegalovirus Infection in Hematopoietic Stem Cell Transplantation Recipients following Letermovir Prophylaxis
AU - Gabanti, Elisa
AU - Borsani, Oscar
AU - Colombo, Anna Amelia
AU - Zavaglio, Federica
AU - Binaschi, Luana
AU - Caldera, Daniela
AU - Sciarra, Roberta
AU - Cassinelli, Gabriela
AU - Alessandrino, Emilio Paolo
AU - Bernasconi, Paolo
AU - Ferretti, Virginia Valeria
AU - Lilleri, Daniele
AU - Baldanti, Fausto
N1 - Funding Information:
Financial disclosure: This work was partially supported by the Fondazione Regionale per la Ricerca Biomedica (Grant FRRB 2015-043), Ministero della Salute, Ricerca Corrente (Grant 8072019), and Ricerca Finalizzata (Grant RF-2019-12370797).
Publisher Copyright:
© 2022 The American Society for Transplantation and Cellular Therapy
PY - 2022
Y1 - 2022
N2 - Letermovir (LTV), recently approved for the prophylaxis of human cytomegalovirus (HCMV) reactivation after hematopoietic stem cell transplantation (HSCT), has been shown to decrease the rate of infection in the first months post-transplantation. The aim of this study was to evaluate the impact of LTV prophylaxis on immune reconstitution and late-onset infection. We studied HCMV infection and HCMV-specific T cell reconstitution in 2 matched groups of HSCT recipients, those treated with LTV prophylaxis (n = 30; LTV group) and those receiving preemptive therapy (n = 31; PET group). We analyzed the rates of graft-versus-host disease (GVHD), neutropenia, baseline disease recurrence, and overall survival in the 2 groups. Clinically significant infections necessitating preemptive therapy showed a similar rate in the 2 groups (PET: 21 of 31 [68%]; LTV: 17 of 30 [57%]; P = .434) but occurred significantly later (after prophylaxis discontinuation) in the LTV group. There was no between-group difference in peak HCMV DNAemia level (P = .232). HCMV-specific T cell recovery was delayed by approximately 100 days in the LTV group. HCMV-specific CD4 and CD8 T cell counts were significantly lower in the LTV group at days 120 to 360 and days 90 to 120, respectively. A lower rate of chronic GVHD (P = .024) was seen in the LTV group. Time to engraftment, rate of disease relapse, and 1-year survival were not different between the 2 groups, whereas trends toward a lower rate of neutropenia (P = .124) and a higher rate of acute GVHD grade III-IV (P = .103) were observed in the LTV group. Because LTV prophylaxis delays HCMV infection and HCMV-specific immune reconstitution, immunologic and virologic monitoring should be implemented after discontinuation of prophylaxis. The potential effect of LTV prophylaxis in reducing chronic GVHD should be evaluated in prospective studies.
AB - Letermovir (LTV), recently approved for the prophylaxis of human cytomegalovirus (HCMV) reactivation after hematopoietic stem cell transplantation (HSCT), has been shown to decrease the rate of infection in the first months post-transplantation. The aim of this study was to evaluate the impact of LTV prophylaxis on immune reconstitution and late-onset infection. We studied HCMV infection and HCMV-specific T cell reconstitution in 2 matched groups of HSCT recipients, those treated with LTV prophylaxis (n = 30; LTV group) and those receiving preemptive therapy (n = 31; PET group). We analyzed the rates of graft-versus-host disease (GVHD), neutropenia, baseline disease recurrence, and overall survival in the 2 groups. Clinically significant infections necessitating preemptive therapy showed a similar rate in the 2 groups (PET: 21 of 31 [68%]; LTV: 17 of 30 [57%]; P = .434) but occurred significantly later (after prophylaxis discontinuation) in the LTV group. There was no between-group difference in peak HCMV DNAemia level (P = .232). HCMV-specific T cell recovery was delayed by approximately 100 days in the LTV group. HCMV-specific CD4 and CD8 T cell counts were significantly lower in the LTV group at days 120 to 360 and days 90 to 120, respectively. A lower rate of chronic GVHD (P = .024) was seen in the LTV group. Time to engraftment, rate of disease relapse, and 1-year survival were not different between the 2 groups, whereas trends toward a lower rate of neutropenia (P = .124) and a higher rate of acute GVHD grade III-IV (P = .103) were observed in the LTV group. Because LTV prophylaxis delays HCMV infection and HCMV-specific immune reconstitution, immunologic and virologic monitoring should be implemented after discontinuation of prophylaxis. The potential effect of LTV prophylaxis in reducing chronic GVHD should be evaluated in prospective studies.
KW - Allogeneic hematopoietic stem cell transplantation
KW - Ganciclovir
KW - Human cytomegalovirus
KW - Letermovir
KW - Preemptive therapy
KW - Prophylaxis
KW - T cell response
KW - Valganciclovir
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UR - http://www.scopus.com/inward/citedby.url?scp=85124906313&partnerID=8YFLogxK
U2 - 10.1016/j.jtct.2022.01.008
DO - 10.1016/j.jtct.2022.01.008
M3 - Article
C2 - 35042012
AN - SCOPUS:85124906313
SN - 2666-6375
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
ER -