Epstein-Barr Virus–Related Post-Transplant Lymphoproliferative Disorders in Cystic Fibrosis Lung Transplant Recipients: A Case Series

Highlights

• The risk of developing post-transplant lymphoproliferative disorders is increased in young cystic fibrosis patients.

• The Epstein-Barr virus serostatus D+/R− is considered a very important risk factor for developing post-transplant lymphoproliferative disorders.

• The transplanted graft is frequently the target of disease involvement.

• A regular Epstein-Barr virus screening in pre– and post–lung transplant follow-up is strongly suggested.

Abstract

Background

Solid organ transplantation is associated with a higher risk of Epstein-Barr virus (EBV)–related lymphoproliferative disease due to immunosuppressive regimen. Little evidence is currently available on post-transplant lymphoproliferative disorders (PTLDs) in the lung transplant (LuTx) setting, particularly in cystic fibrosis (CF) recipients.

Methods

We retrospectively analyzed all the cases of PTLDs that occurred in our LuTx center between January 2015 and December 2017. We reviewed clinical and radiologic data, donor and recipient EBV serostatus, immunosuppressive therapy, histologic data, and follow-up of these patients.

Results

A total of 77 LuTxs were performed at our center in the study period; 39 (50.6%) patients had CF; 4 developed EBV-related PTLDs. They were all young (17–26 years) CF patients with high serum EBV DNA load. Disease onset was within the first 3 months after LuTx. In 3 cases presentation was associated with fever and infection-like symptoms, whereas in 1 case radiologic suspicion arose unexpectedly from a CT scan performed for different clinical reasons. Diagnosis was reached through lung biopsy in all cases. All patients received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin), vincristine sulfate (Oncovin), and prednisone with variable response and complications.

Conclusion

In our experience, the early development of EBV-related PTLD was a highly aggressive, life-threatening condition, which exclusively affected young CF patients in the early post-transplant period. The rate of this complication was relatively high in our population.

Diagnosis with lung biopsy is crucial in all suspected cases and regular monitoring of EBV DNA levels is of utmost importance given the high correlation with PTLDs in patients at increased risk.