Infectious Complications and Mortality in Post-Transplant Lymphoproliferative Disorder Following Solid Organ Transplantation: Experiences of 10 Years in a Single Center

Abstract

Introduction: An estimated 2 to 20% of patients with solid organ transplants (SOT) are later diagnosed with post-transplant lymphoproliferative disorder (PTLD). These patients receive immunosuppression therapy for SOT, however, there is a paucity of research examining the infection complications and morbidity in those diagnosed with PTLD. Our single center study examined infections following a PTLD diagnosis and the potential risk of morbidity. Methods: We reviewed the Cleveland Clinic electronic medical record (EMR) of SOT patients who were diagnosed with PTLD between 2010 and 2020. 98 patients met the inclusion criteria. These were further stratified by transplant type: 26 liver, 24 renal, 22 lung, 19 heart, and 2 combined heart and lung transplant patients. All data were analyzed using R software. Results: The mean onset of biopsy confirmed PTLD following transplant was 7.13 ± 7.28 years,. Abdominal pain was the most common presenting symptom prompting further work up, seen in 29% of patients. Patients were also diagnosed based on other chief complaints, including fatigue (n = 20), weight loss (n = 16), and fever (n = 14). Additionally, a smaller subset of patients were diagnosed incidentally on imaging. The most frequent primary site of PTLD was the lymphoid tissue / enlarged lymph nodes (34% of patients) and followed by gastrointestinal tract (29%). Elevated lactate dehydrogenase was present in 42% of patients, diagnostic criteria for acute kidney injury in 23%, and hyperuricemia was noted in 16%. Diffuse large B-lymphoma was the most common subtype diagnosed in 72 of 98 patients followed by EBV related. After diagnosis, 60% of PTLD patients presented to the hospital due to infections, with a mean of 49.9 ± 55.3 days following PTLD diagnosis. Of those patients, bacterial infections were the most common (49.3%), followed by viral infections (34.5%), fungal infections (14.9%), and parasitic infections (1.15%). The bacterial infections were predominantly encapsulated organisms including Pseudomonas aeruginosa (33%), Escherichia coli (19%), and Streptococcus pneumoniae (14%). Rituximab was used in 40% of patients following diagnosis while rituximab, cyclophosphamide, doxorubicin, and vincristine (R-CHOP) was used in 41% of patients. There was no significant difference in infection risk in the first 100-days, following initiation of rituximab infections were seen in 33%, while the infection risk with R-CHOP was 35% (p = 0.31). Moreover, the most common cause of death was infection seen in 39% of patients, while PTLD itself with progressive disease was the second most common cause of death in 27%. The 6-month mortality following PTLD was 16% with 56% of those deaths being attributed to infection. The one-year mortality rate following PTLD was 25% with 48% of those being attributed to infection. Conclusions: In patients with PTLD diagnosis, the most common cause of death was infection (39%), followed by complications related to PTLD such as progressive disease with multi-organ failure. High serious infection risk may be due to aberrant monoclonal B-cell proliferation which paradoxically leads to decreased cellular immunity. The increased risk of B-cell PTLD in patients with SOT is likely due to the chronic immunosuppression, where patients gain acquired somatic driver mutations leading to a malignant state yet with an increased infection risk. Additionally, there was no difference in infection at 100 days between rituximab chemotherapy compared to R-CHOP. This necessitates the question of initiating viral, bacterial and fungal infection prophylaxis, similar to that following splenectomy or post BMT, should be implemented in patients diagnosed with PTLD. Further larger prospective studies are needed to further analyze the potential need and benefit of prophylactic vaccinations at the time of diagnosis in the PTLD patient population.