title: Effects of intensified conditioning on Epstein-Barr virus and cytomegalovirus infections in allogeneic hematopoietic stem cell transplantation for hematological malignancies.
abstract: 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.
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xuan
authors.forename: Fen
authors.initials: F
authors.lastname: Huang
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Fan
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Zhou
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.forename: Guopan
authors.initials: G
authors.lastname: Yu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Can
authors.initials: C
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Qifa
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003587:Cytomegalovirus / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000209:etiology* / Q000401:mortality / Q000628:therapy; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000209:etiology* / Q000401:mortality / Q000628:therapy; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000401:mortality*; D014184:Transplantation, Homologous; D014766:Viremia / Q000209:etiology / Q000628:therapy; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D012333:RNA, Messenger