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

Abstract

BackgroundIntensified 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.MethodsA 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.ResultsThe 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).ConclusionsIntensified 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.

Sequential intensified conditioning followed by prophylactic DLI could reduce relapse of refractory acute leukemia after allo-HSCT

“…GVHD prophylaxis was described in our reports [15, 38]. CsA alone or CsA plus methotrexate (MTX) were administered in patients undergoing HLA-matched sibling donor transplants.…”

“…Ganciclovir was given for 2 weeks pre-transplantation for prophylaxis of CMV infection, and was administered once again when CMV-emia occurred [4]. Preemptive therapy for EBV-emia was according to our previous description [38, 41]. Antifungal agents were administered 5 days pre-transplantation and continued for +30 to +90 days post-transplantation or disease control according to the history and state of IFD pre-transplantation [42].…”

A comparison of lamivudine vs entecavir for prophylaxis of hepatitis B virus reactivation in allogeneic hematopoietic stem cell transplantation recipients: a single-institutional experience

“…CsA+MTX+ATG (total ATG doses of 7.5 to 10 mg/kg, on days − 3 to 0)+mycophenolate were used in patients undergoing haploidentical related donor transplants for GvHD prophylaxis. 11 Nucleoside drug therapy Generally, the choice of antiviral drugs was determined by the responsible physician according to the standards of clinical practice at the authors' institute and local prescribing guidelines. On a daily basis, 100 mg lamivudine was administered orally, and 0.5 mg entecavir was administered orally each day.…”

Effect of HHV-6 and HHV-7 Infection on the Posttransplant Process and the Development of Complications in Patients after Autologous Stem Cell Transplantation / HHV-6 Un HHV-7 Infekcijas Ietekme Uz Pēctransplantācijas Klīnisko Gaitu Un Komplikāciju Attīstību Pacientiem Pēc Autologas Cilmes Šūnu Transplantācijas

“…Major complications after allo-HSCT are caused by CMV and EBV (Anonymous, 2008;Ljungman et al, 2010;Xuan et al, 2012). Widespread use of antiviral pre-emptive therapy has markedly diminished the incidence of CMV-related and EBV complications in transplant patients during the early period after HSCT.…”