Effects of intensified conditioning on Epstein-Barr virus and cytomegalovirus infections in allogeneic hematopoietic stem cell transplantation for hematological malignancies

Background: Intensified conditioning regimens (increasing the intensity of standard myeloablative conditioning) for hematological malignancies in allogeneic hematopoietic stem cell transplantation (allo-HSCT) could reduce the relapse rate of the underlying disease, but it might simultaneously increase the transplant-related mortality including the mortality of infections. To explore whether intensified conditioning affected Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections, 185 patients undergoing allo-HSCT were enrolled. Methods: A total of 104 cases received standard and 81 intensified conditioning. Cyclosporine A (CsA) withdrawal and/or donor lymphocyte infusion (DLI) were conducted in high-risk patients. The EBV-DNA and CMV-DNA levels of blood were monitored regularly by quantitative real-time polymerase chain reaction (RQ-PCR) and immune reconstitution of recipients were analyzed by flow cytometry. Results: The 3-year cumulative incidence of EBV viremia, EBV-associated diseases and mortality of EBV-associated diseases were 25.3%+/- 4.6%, 10.5%+/- 3.4% and 0.0%+/- 0.0% in the standard group, compared with 45.6%+/- 6.5%, 26.0%+/- 5.3% and 7.3%+/- 3.1% in the intensified group (P=0.002, P=0.002, P=0.008). The 3-year cumulative incidence of CMV viremia and CMV-associated diseases, mortality of CMV-associated diseases and incidence of bacterial and fungal infections were similar between the two groups (P=0.855, P=0.581, P=0.933, P=0.142, P=0.182, respectively). Multivariate analysis showed that intensified conditioning was one of the risk factors for EBV viremia and EBV-associated diseases (P=0.037, P=0.037), but it had no effects on CMV infections. The percentage of CD4(+) T cells and CD4(+)/CD8(+) ratio at 3 months post-transplantation were lower in the intensified group (P=0.032, P=0.022). The 3-year OS and DFS in the standard group were 62.2%+/- 5.8% and 60.6%+/- 5.6%, compared with 51.6%+/- 6.2% and 51.1% +/- 5.9% in the intensified group (P=0.029, P=0.063). Conclusions: Intensified conditioning represents a promising approach for high-risk hematological malignancies, although it affects early immune reconstitution of recipients and increases the incidence and mortality of EBV infections.