The time-dependent effects of early-onset Epstein-Barr viremia on adult acute leukemia patients following allo-HSCT with ATG-containing MAC regimen

Ann Hematol. 2021 Jul;100(7):1879-1889. doi: 10.1007/s00277-021-04528-6. Epub 2021 Apr 22.

Abstract

Epstein-Barr virus (EBV) viremia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The purpose of this study was to evaluate the impacts of early-onset EBV viremia in acute leukemia (AL) patients who underwent allo-HSCT with anti-thymocyte globulin (ATG)-containing myeloablative conditioning (MAC) regimen. Two hundred and ninety-six patients were included between January 2013 and December 2015. In 126 patients (42.6%) who developed early-onset EBV viremia, with a median time of 48 (range 18~99) days after allo-HSCT. The cumulative incidence of EBV viremia at 30 and 90 days after allo-HSCT were 4.1 and 39.9%, respectively. Prognostic analysis showed that the adjusted overall survival in early-EBVpos group was significantly lower than early-EBVneg group within the first 26.7 months after allo-HSCT [hazard ratio (HR), 1.63, P = 0.012], but significantly higher than those afterward (after 26.7 months: HR 0.11, P = 0.035); for the adjusted event-free survival, early-EBVpos group was significantly inferior in early-EBVpos group within the first 10.8 months after transplantation (HR: 1.55, P = 0.042), and this adverse effect was not detected any more after 10.8 months (HR: 0.58, P = 0.107). Compared with early-EBVneg group after adjusting by aGVHD and CMV viremia, HR for death from transplant-related mortality was 2.78-fold higher in patients with early-EBV viremia in piecewise constant Cox analysis (P = 0.006), and this adverse effect was not detected any more after the cut-point time (HR: 0.67, P = 0.361). No differences in terms of relapse and relapse mortality were observed between early-EBVpos and early-EBVneg group (P > 0.05). In conclusion, the impacts on transplant outcomes of early-EBV viremia were time-dependent, which may help to optimize management strategies for early-EBV viremia after allo-HSCT, especially in AL patients with ATG-containing MAC regimen.

Keywords: ATG; Acute leukemia; Allogeneic hematopoietic stem cell transplantation; Early viremia; Epstein-Barr virus; Prognosis.

MeSH terms

  • Adult
  • Allografts
  • Antilymphocyte Serum / adverse effects*
  • Cytomegalovirus / drug effects
  • Cytomegalovirus / physiology
  • Cytomegalovirus Infections / complications
  • Cytomegalovirus Infections / virology
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / virology*
  • Female
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation*
  • Herpesvirus 4, Human / drug effects*
  • Herpesvirus 4, Human / physiology
  • Histocompatibility
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Leukemia, Myeloid, Acute / complications
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Myeloablative Agonists / adverse effects*
  • Myeloablative Agonists / therapeutic use
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Prognosis
  • Proportional Hazards Models
  • T-Lymphocytes / immunology
  • Time Factors
  • Transplantation Conditioning / adverse effects*
  • Unrelated Donors
  • Viremia / etiology*
  • Virus Activation / drug effects*
  • Young Adult

Substances

  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Myeloablative Agonists