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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

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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.

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Funding

This work was partially supported by grants from the National Natural Science Foundation of China (81770203 to D-H L, 81670135 and 81870109 to X-N G), Natural Science Foundation of Beijing (7162174 to J L) and National Clinical Specialist Focus on Military Construction Projects.

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Author notes

  1. Xiao-Ning Gao, Ji Lin and Li-Jun Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Chinese PLA General Hospital, Medical School of Chinese PLA, 28 Fuxing Road, Beijing, 100853, China

    Xiao-Ning Gao, Li-Jun Wang, Fei Li, Hong-Hua Li, Shu-Hong Wang, Wen-Rong Huang, Chun-Ji Gao, Li Yu & Dai-Hong Liu

  2. Institute of Basic Medicine, Chinese PLA General Hospital, Medical School of Chinese PLA, 28 Fuxing Road, Beijing, 100853, China

    Ji Lin

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  1. Xiao-Ning Gao
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Correspondence to Xiao-Ning Gao or Dai-Hong Liu.

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This study was approved by the Ethics Committee of Chinese PLA General Hospital, and signed informed consents were obtained from all patients prior to transplantation in accordance with principles of Declaration of Helsinki.

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Gao, XN., Lin, J., Wang, LJ. et al. 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. Ann Hematol 98, 2163–2177 (2019). https://doi.org/10.1007/s00277-019-03742-7

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