Post-transplant malignancy: Focusing on virus-associated etiologies, pathogenesis, evidence-based management algorithms, present status of adoptive immunotherapy and future directions

Table 4 Risk factors associated with post-transplant lymphoproliferative disorders [35,45,52,141,142]

Risk factors of PTLD in KT	Likely cause/association
Recipient age < 10 yr	A greater likelihood of being seronegative for EBV
Recipient age > 60 yr	Associated finding in various studies
EBV seropositive donor to EBV seronegative negative recipient (EBV D+/R-)	90% are donor derived and 10–76-fold higher incidence of early PTLD
Bimodal peak	First peak (with higher incidence) in first 2 years and 2nd peak between 5 to 10 years post-transplant
Intensity of immunosuppression and use of T cell depleting antibodies (ATG and/or OKT3), belatacept	Reduction in cancer immunosurveillance
Treated acute rejection within first year after transplantation with depleting antibodies	Reduction in cancer immunosurveillance
Simultaneous pancreas–kidney transplantation	Association
HLA mismatches (especially HLA B and DR mismatches)	Likely, due to higher associated risk of rejection and use of increased net immunosuppression

PTLD: Post-transplant lymphoproliferative disorders; KT: Kidney transplantation; EBV: Epstein–Barr virus; HLA: Human leukocyte antigen; ATG: Antithymocyte globulin; OKT3: Trade name of Monomurab CD3 (a murine monoclonal antibody reacting with CD3 molecule on human T lymphocyte).