Complete response to switch immunodepression of late-onset post-transplant lymphoproliferative disease (PTLD)

Martín-Aguilar, Sara; López-Rodríguez, Estefanía; Puentes-Zarzuela, Maria Carmen

doi:10.1016/j.medcle.2023.03.012

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Post-transplant lymphoproliferative disease (PTLD) is the second most frequent post-transplant malignancy in adults which accounts for between 40 and 70% mortality. It usually presents from months after transplantation to several years later, average 6 months. The symptoms are usually non-specific and extranodal involvement predominates.<a class="elsevierStyleCrossRefs" href="#bib0030">1,2</a>Case presentationA 46-year-old man with personal history of arterial hypertension, dyslipidemia, and hyperuricemia, who received a kidney transplant in 1997 due to interstitial nephropathy secondary to vesicoureteral reflux. The patient was initially treated with cyclosporine, mycophenolate mofetil and prednisone, having to change cyclosporine to tacrolimus 2 months after transplantation (due to toxicity with graft dysfunction) and discontinuing mycophenolate mofetil 8 months after transplantation due to repeated urinary tract infections, one of which need hospital admission. He presented post-trasplant suboptimal renal function (creatinine 2.2mg/dl), and non-significant proteinuria (1.8g/day) with a good response to antiproteinurics.In a control ultrasound on 09/2021, abdominal lymph nodes were detected, completing study with CT, 18F-FDG (18F-fluoro-2-deoxy-d-glucose) PET-CT (which showed multiple hypermetabolic lymph nodes increased in size supra and infradiaphragmatic and increased splenomegaly, suggestive of lymphoproliferative process) and right supraclavicular adenopathy biopsy (with the result of monotypic post-transplant polymorphic lymphoproliferative disorder). Serology was analyzed for Cytomegalovirus and Eibstein-barr Virus (EBV), both being IgG+. It was decided to change immunodepressive treatment, gradually replacing tacrolimus with sirolimus. The re-evaluation PET-CT on 02/2022 showed disappearance of all hypermetabolic adenopathies, with small residual adenopathies and little uptake at the cervical, supraclavicular and retroperitoneal levels.It was decided to maintain immunodepressive treatment with prednisone and sirolimus and a new analytical follow-up, ruling out the additional administration of chemotherapy or rituximab.Discussion and conclusionsEarly detection of PTLD is associated with improved outcome, nevertheles, its debuts with non-specifics symtoms and uncharacteristic findings on conventional imaging challenges achieving an early diagnosis.<a class="elsevierStyleCrossRefs" href="#bib0030">1–3</a>18F-FDG PET-CT is an established imaging modality in FDG-avid lymphomas, with high diagnostic accuracy (90% sensitivity, 91% specificity) and therapeutic impact. Diferents studies demostrated its use for detecting PTLD, therefore it can become an essential tool for its diagnostic and follow-up, specially due to the ability of PET-CT to detect extranodal disease and differentiate malignancy from benign lesions.<a class="elsevierStyleCrossRefs" href="#bib0030">1–3</a> Nevertheles, its use has not been extensively evaluated in this disease and it's not yet standardized.<a class="elsevierStyleCrossRefs" href="#bib0030">1,3,4</a>PET/CT is also the standard for remission assessment of FDG-avid lymphomas, therefore it may be the choice for evaluating response to treatment in PTLD,<a class="elsevierStyleCrossRefs" href="#bib0035">2,4</a> remarkably to differentiate tumor remnants from fibrosis/necrosis, avoiding the need for histological confirmation due to its high negative predictive value (specially in multiple residual lesions, as multiple biopsies are impractical).<a class="elsevierStyleCrossRefs" href="#bib0030">1,2</a>Immunodepressive therapy have reduced the risk of rejection in kidney transplant, however PTLD is a common complications<a class="elsevierStyleCrossRef" href="#bib0045">4</a>; the major risk factors are immune status for EBV infection, human leukocyte antigen mismatching, T-cell depletion and type and cumulative effect of immunodepressive regimens.<a class="elsevierStyleCrossRefs" href="#bib0030">1–3</a> Immunodepressive drugs inhibit the function of EBV-induced B-cell proliferation of lymphocytes and T-cells and, as long as the predominant histology in PTLD is diffuse large B cell lymphoma, reduction or withdrawal of immunodepression is the first treatment option. Other treatments such as rituximab, chemo-radiotherapy and antiviral agents can be considered, however, the optimal strategy remains undetermined.<a class="elsevierStyleCrossRefs" href="#bib0030">1,2,5</a>In this case, the patient achieved a complete remission just changing gradually the type of immunodepressant (tacrolimus for sirolimus).Recent studies<a class="elsevierStyleCrossRef" href="#bib0050">5</a> showed that calcineurin inhibitors (as Tacrolimus) increase the risk of EBV-related disease, whereas imTOR (as Sirolimus) have an anti-proliferative effect in B-cells EBV-infected growth and prevent/treat PTLD without graft rejection, inducing apoptosis, inhibiting interleukin-10 secretion and causing cell cycle arrest in tumor cells.In conclusion, PTLD is a rare complication with great morbidity-mortality in solid organ transplants. In this case, we demonstrate the possibility of obtaining a complete remission just changing the type of immunodepression, as well as the capacity of 18F-FDG PET-CT to detect it and monitor the response to treatment. However, follow-up after PTLD resolution is short, so these results must be validated through a more in-depth and larger studies.Authors’ contributionsEL-R and SM-A analyzed and interpreted the PET-TC studies. SM-A collected and analyzed the data from the clinical history and from the different diagnostic tests and was a major contributor in writing the manuscript. All authors read and approved the final manuscript.FundingThe authors declare that they have no sources of funding.Conflict of interestsThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper." 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Vol. 161. Issue 2.

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