Case 1
A previously healthy 12-year-old female underwent orthotopic heart
transplant (OHT) for dilated cardiomyopathy. Pre-transplant serologies
were EBV donor positive/recipient negative. She received postoperative
immunosuppression with anti-thymocyte globulin (ATG) and corticosteroids
and was maintained on tacrolimus and mycophenolate mofetil (MMF). She
presented approximately 38 months post OHT with altered mental status,
weight loss, nausea and diarrhea. Central nervous system (CNS) imaging
revealed a left temporal ring enhancing lesion which was found to be EBV
Post-Transplant Lymphoproliferative disorder (PTLD). Serum EBV levels
peaked at 11,848 copies/mL around time of diagnosis. Further imaging
revealed a two cm lesion in the right hepatic dome and another one cm
lesion in the right inferior hepatic lobe, presumed to be additional
PTLD lesions (Fig 4). Immunosuppression was subsequently reduced, and
she was started on PTLD directed chemotherapy with rituximab,
methotrexate, cyclophosphamide, and triple intrathecal
therapy10.
Repeat imaging one month following therapy showed interval improvement
of her CNS PTLD, but demonstrated interval growth of the liver lesions,
with increased FDG avidity on PET and newly visualized left kidney
lesions (Fig 4). Due to the presumed discrepant response, an
ultrasound-guided liver biopsy was performed which revealed hepatic
EBV-SMT (Fig 1). At diagnosis, EBV PCR was negative in the peripheral
blood with less than 200 copies/mL found in the cerebrospinal fluid;
likely due from PTLD directed treatment effects. Her tacrolimus was
changed to sirolimus and her mycophenolate was discontinued in an effort
to reduce overall immunosuppression and provide potential antitumor
effect through mammalian target of rapomycin (mTOR)
inhibition7. She went on
to receive 4,500 cGy whole brain radiation and EBV targeted cytotoxic
T-lymphocyte (CTL)
therapy11. CNS
remission of her PTLD was achieved approximately 1.5 years after
diagnosis and EBV liver lesions remain stable at approximately six years
post EBV SMT diagnosis. She was restarted on tacrolimus due to mild
acute cellular rejection and remains currently on a combination of
sirolimus and tacrolimus for immunosuppression.