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Risk factors and clinical outcomes of Epstein-Barr virus DNAemia and post-transplant lymphoproliferative disorders after haploidentical and matched-sibling PBSCT in patients with hematologic malignancies.

Abstract
In allogeneic hematopoietic stem cell transplantation recipients, reactivation of Epstein-Barr virus (EBV) can cause post-transplantation lymphoproliferative disorder (PTLD), which may rapidly progress to multiorgan failure and even death. Development of EBV PTLD correlates very closely with use of anti-thymocyte globulin (ATG) and type of transplant. To assess the incidences and clinical features of EBV DNAemia and PTLD in the setting of stem cell transplantation using unmanipulated G-CSF-primed allogeneic peripheral blood stem cells as graft, we performed a retrospective analysis of stem cell transplantation from HLA-matched sibling donors (MSD-SCT, n = 90) or HLA-haploidentical related donors (HID-SCT, n = 110) in patients with hematological malignancies. All of HID-SCT recipients and 27.8% of MSD-SCT recipients received an ATG-containing conditioning regimen. One-year cumulative incidence of EBV DNAemia was 44.1%, ranging from 4.8% in MSD-SCT recipients not using ATG to 20.0% in MSD-SCT recipients using ATG, and 73.7% in HID-SCT recipients. Risk factors for EBV reactivation included use of ATG (p = 0.008), male donor (p = 0.034), and cytomegalovirus DNAemia (p < 0.001). One-year incidence of EBV PTLD was 11.9%, ranging from 1.8% in recipients of MSD-SCT not using ATG to 4.4% in recipients of MSD-SCT using ATG, and 23.5% in recipients of HID-SCT. Risk factors for PTLD after HID-SCT included in fludarabine-containing conditioning regimen (p = 0.010), cytomegalovirus DNAemia (p = 0.036), and patient's age < 40-yr (p = 0.032). Two-year non-relapse mortality was higher for patients with EBV DNAemia than those without EBV DNAemia (35.8% vs. 15.3%, p = 0.002). One-year relapse-free survival and overall survival among patients with PTLD were 40.2% and 44.9%, respectively, as opposed to 63.4% and 68.4% among patients without PTLD (both p < 0.05). In multivariate analyses, EBV DNAemia predicted a lower risk of relapse (p = 0.025), while PTLD was a marginally significant predictor of relapse (p = 0.092). This study identified patients at risk of EBV reactivation and PTLD after unmanipulated allogeneic peripheral blood stem cell transplantation.
AuthorsXiao-Ning Gao, Ji Lin, Li-Jun Wang, Fei Li, Hong-Hua Li, Shu-Hong Wang, Wen-Rong Huang, Chun-Ji Gao, Li Yu, Dai-Hong Liu
JournalAnnals of hematology (Ann Hematol) Vol. 98 Issue 9 Pg. 2163-2177 (Sep 2019) ISSN: 1432-0584 [Electronic] Germany
PMID31243569 (Publication Type: Clinical Trial, Journal Article, Observational Study)
Chemical References
  • DNA, Viral
Topics
  • Adolescent
  • Adult
  • Allografts
  • Child
  • DNA, Viral (blood)
  • Disease-Free Survival
  • Epstein-Barr Virus Infections (blood, mortality, therapy)
  • Female
  • Hematologic Neoplasms (blood, mortality, therapy, virology)
  • Herpesvirus 4, Human (metabolism)
  • Humans
  • Lymphoproliferative Disorders (blood, mortality, therapy, virology)
  • Male
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation
  • Retrospective Studies
  • Risk Factors
  • Siblings
  • Survival Rate
  • Transplantation Conditioning

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