PTLD requires a high index of suspicion and must be on your radar. Early disease is often easily managed by lowering immunosuppression, but late detection is a disaster. Clinical presentations vary from a benign infectious mononucleosis syndrome to a severe malignant lymphoproliferative disorder; 3 distinct clinical syndromes are described:
1. Polyclonal B-cell proliferation with malignant transformation, widespread disease, and multiorgan involvement. This accounts for 30% of patients and presents within weeks of transplant. You’re less likely to miss this presentation, as patients are often closely monitored during this time.
2. The majority of cases (over 50%) present as an infectious mononucleosis within a year of transplant. This is due to a benign polyclonal proliferation of B cells. This is easily missed, which is a tragedy as this presentation is very responsive to lowering immunosuppression.
3. A minority present late with a monoclonal B-cell proliferation, extra-nodal disease, and visceral involvement late post-transplant.
- Of those EBV D+/R- recipients who were not monitored (n=6), 50% developed PTLD and lost their transplants
- Of the remainder, 60% developed EBV viremia and had their immunosuppression reduced; only 1 developed PTLD. This underscores how efficacious reducing immunosuppression can be.
- 6/20 with persistent viremia received rituximab; none got PTLD or lost their transplant. This needs to be replicated but is very encouraging.
- The graft is a commonly affected site. Isolated allograft dysfunction can be a presentation PTLD, as is allograft dysfunction developing after an increase in immunosuppression.
- Check EBV in all flu-like illnesses; doubly so if lymphadenopathy is present; triply so if during the first post transplant year.
- Antivirals don’t work. EBV do not express thymidine kinase, the target of ganciclovir/acyclovir
- Reducing immunosuppression does work, if instituted early. A typical regimen would be to cut CNI by 50%, discontinue MMF/AZA, and continue the same or 50% less steroid
- Main risk factor is the EBV D+/R- recipient, and they need monitoring for EBV infection. Other risk factors include extremes of age, heavier immunosuppression especially anti-lymphocyte antibody use and CMV infection