PTLD (1): Solid Organs
- NHL accounts for 93% of post Tx lymphomas, mostly B-cell type.
- Rarely from T-cells, even rarer from Tc-cells.
Pathogenesis:
- B-cell proliferation induced by EBV infection, although can occur in EBV -ve disease.
- EBV mRNA found in hepatic disease prior development of overt PTLD.
- Most PTLD cells are of host origin. Recipient-origin PTLD presents as a multi-system disease, usually presenting later (>5 yrs post Tx) with poorer prognosis. Donor-origin PTLD usually regresses after withdrawl of immunosuppression (IS).
Clinical Features:
- Three types of EBV-related PLTD:
- Benign polyclonal lymphoproliferation: Infectious mononucleosis type illness - develops 2-8 weeks after immunosuppresion. Polyclonal B-cell proliferation with normal cytogenetics & no evidence of malignant transformation.
- 30% of cases present similar to the first, but with evidence of early transformation.
- 15% of cases present with extranodal disease with local solid tumors showing monoclonal B cell proliferation with malignant cytogenetic abnormalities and Ig gene re-arrangements.
- >50% of PTLD patients present with extranodal disease, including a higher incidence of CNS disease cf. general population.
- Tumors not due to EBV present much later.
Risk factors:
- Degree of IS.
- Level of induction, incidence higher in the first year, when the use of IS is greater.
- Incidence in the use of tacrolimus is much greater than MMF.
- Cardiac>renal Tx as the degree of IS and consequences of rejection are greater.
- Use of OKT3.
- EBV status of recipient.
- HLA mismatch.
- Time post transplant: highest in the first year.
- Recipent age. Higher incidence in children, who are EBV(-) prior to Tx.
- Ethnicity.
Diagnosis:
Best method is via wedge biopsy, allowing adequate tissue.
- Disruption of underlying tissue architecture by a lymphoproliferative process.
- Presence of mono- or oligoclonal populations as determined by cellular or viral markers.
- EBV infection of many cells.
- CNS PTLD: new neurology, CT (lesions enhance with gadolinium), CSF for EBV PCR.
- EBV viral load is of quesionable value.
- Monoclonal gammopathy in the urine has been shown to be correlated with PTLD.
Prevention:
- Limiting IS & tapering doses.
- Early diagnosis of acute EBV infection by PCR, followed by anti-viral therapy (gancyclovir).
Treatment:
- Reduction in IS: for polyclonal PTLD, disease may regress as IS is reduced.
- If severely ill with extensive disease, stop IS and use pred.
- Anti-viral Rx: acyclovir, polyclonal disease responds to gancyclovir.
- Anti-B cell monoclonal Ab (Rituximab - anti-CD20).
- Chemotherapy: e.g CHOP or DxT.
- IFN-α: limited experience. May cause irreversible acute rejection, e.g. risk of HCV.
AMH.
