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Review
. 2020 Feb 1;12(2):328.
doi: 10.3390/cancers12020328.

Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disorders after Hematopoietic Stem Cell Transplantation: Pathogenesis, Risk Factors and Clinical Outcomes

Ayumi Fujimoto  1 , Ritsuro Suzuki  1
Affiliations
Review

Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disorders after Hematopoietic Stem Cell Transplantation: Pathogenesis, Risk Factors and Clinical Outcomes

Ayumi Fujimoto et al. Cancers (Basel). .

Abstract

Epstein-Barr virus (EBV) is a ubiquitous virus belonging to the human -herpes virus subfamily. After primary infection, EBV maintains a life-long latent infection. A major concern is that EBV can cause a diverse range of neoplasms and autoimmune diseases. In addition, patients undergoing hematopoietic stem cell transplantation or solid organ transplantation can experience post-transplant lymphoproliferative disorders (PTLDs) due to dysfunction or suppression of host's immune system, or uncontrolled proliferation of EBV-infected cells. In recent years, the number of EBV-associated PTLD cases has increased. This review focuses on the current understandings of EBV-associated PTLD pathogenesis, as well as the risk factors and clinical outcomes for patients after allogeneic stem cell transplantation.

Keywords: hematopoietic stem cell transplantation; pathogenesis; post-transplant lymphoproliferative disorder; risk factors.

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Conflict of interest statement

A.F. has received honoraria from Bristol-Meyer Squib and Celgene. R.S. has received honoraria from Bristol-Meyer Squib, Novartis, Kyowa-Hakko Kirin, Chugai Pharmaceuticals, Shionogi, Takeda, Meiji Seika Pharma, MSD, Otsuka, Sawai, Celgene, Sumitomo Dainippon, Eisai Pharmaceuticals, Alexion Pharma, Sanofi, Gilead Sciences, Abbvie Inc., Mundi Pharma, Jazz Pharma, Ono Pharma, and Janssen Pharmaceuticals.

Figures

Figure 1
Figure 1
Pathogenesis of EBV-related PTLD after allogeneic stem cell transplantation. EBV-encoded oncogenes such as LMP 1 and LMP2; host immunosuppression due to the conditioning regimen; use of immunosuppressive agents; and growth advantages obtained by EBV-infected lymphocytes induced by genetic or epigenetic aberrations play an important role for development of PTLD. Persistent immune activation and chronic inflammation induced by the conditioning regimen and graft-versus-host disease also contribute to PTLD development. Abbreviations: HSCT, hematopoietic stem cell transplantation; GVHD, graft-versus-host disease; DAMPs, damage-associated molecular patterns; PAMPs, Pathogen-associated molecular patterns; IL-1, interleukin-1; TNF-αtumor necrosis factor-α; LPS, lipopolysaccharide; EBV, Epstein-Barr virus; LMP, latent membrane protein; EBNA, Epstein-Barr virus nuclear antigen; PTLD, post-transplant lymphoproliferative disorder.
Figure 2
Figure 2
PTLD risk classification. Points are assigned to each risk factor: ATG use in the conditioning regimen (high dose, 2 points; low dose, 1 point), donor type (HLA-mismatched related donor, 1 point; unrelated donor, 1 point; cord blood, 2 points), and primary disease (aplastic anemia, 1 point). Based on the total number of points, the estimated incidence of PTLD at 2 years after HSCT is as follows: low risk (0–1 point), probability 0.3%; intermediate risk (2 points) probability 1.3%; high risk (3 points) probability 4.6%; very high risk (4–5 points) probability 11.5%. Abbreviations: PTLD, post-transplant lymphoproliferative disorder; HSCT, hematopoietic stem cell transplantation.
Figure 3
Figure 3
Hematoxylin and eosin staining of PTLD tissue samples from the central nervous system (×40 magnification). (A) Polymorphic PTLD. (B) Monomorphic PTLD. Abbreviations: PTLD, post-transplant lymphoproliferative disorder.
See this image and copyright information in PMC

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