Viral and Fungal Infections Early After HLA-Mismatched Hematopoietic Stem Cell Transplantation Using Low-Dose Antithymocyte Globulin in High-Risk Patients With Hematological Malignancies Not in Remission.

Abstract

Background: In vivo T-cell depletion with antithymocyte globulin (ATG), especially at high-doses has been shown to be associated with increased incidence of infections after allogeneic hematopoietic stem cell transplantation (HSCT). However, it remains unclear whether ATG, even at low-doses increases the risk of posttransplant infections in the high-risk HSCT setting.

Patients and methods: We conducted a single-center retrospective study of viral and fungal infections early after transplantation, using the data from 82 patients with hematological malignancies. Among them, 42 underwent HLA-mismatched HSCT using low-dose (2.5 mg/kg n = 41, 2.0 mg/kg n = 1) thymoglobulin (ATG patients), and 40 control patients received HSCT without ATG (non-ATG patients) during the same period. Cord blood transplantation patients were excluded. All ATG patients had hematological malignancies not in remission at the time of transplantation, and were considered to be at high-risk for posttransplant infections.

Results: There were no appreciable between-group differences in the incidence of clinically significant cytomegalovirus infection (csCMVi), late-onset CMV reactivation after discontinuation of letermovir, invasive fungal diseases or Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disease. Peak values of CMV antigenemia were almost equal in ATG and non-ATG patients. The prevention of csCMVi with letermovir was constant in the 2 groups. However, ATG patients showed earlier reactivation of CMV and higher incidence of EBV viremia than non-ATG patients. Among their underlying diseases, mature T-cell neoplasm was a significant risk factor for CMV/EBV reactivation.

Conclusion: The use of low-dose thymoglobulin in HLA-mismatched HSCT for nonremission hematological malignancies is a reasonable strategy under careful monitoring for viral reactivation.