Gastrointestinal manifestations, risk factors, and management in patients with post-transplant lymphoproliferative disorder: A systematic review.

BACKGROUND: Patients with a history of solid organ transplantation (SOT) or hematopoietic stem cell transplantation (HSCT) are at an increased risk of developing post-transplant lymphoproliferative disorder (PTLD). The gastrointestinal (GI) tract is commonly affected as it has an abundance of B and T cells. AIM: To determine typical GI-manifestations, risk factors for developing PTLD, and management. METHODS: Major databases were searched until November 2021. RESULTS: Non-case report studies that described GI manifestations of PTLD, risk factors for developing PTLD, and management of PTLD were included. Nine articles written within the last 20 years were included in the review. All articles found that patients with a history of SOT, regardless of transplanted organ, have a propensity to develop GI-PTLD. CONCLUSION: GI tract manifestations may be nonspecific; therefore, consideration of risk factors is crucial for identifying GI-PTLD. Like other lymphoma variants, PTLD is very aggressive making early diagnosis key to prognosis. Initial treatment is reduction of immunosuppression which is effective in more than 50% of cases; however, additional therapy including rituximab, chemotherapy, and surgery may also be required.

Post-transplant lymphoproliferative disorders (PTLD)-from clinical to metabolic profiles-a single center experience and review of literature.

Post-transplant lymphoproliferative disorders (PTLD) are among the most serious complications after solid organ transplantation (SOT). Monomorphic diffuse large B-cell lymphoma (DLBCL) is the most common subtype of PTLD. Historically, outcomes of PTLD have been poor with high mortality rates and allograft loss, although this has improved in the last 10 years. Most of our understanding about PTLD DLBCL is extrapolated from studies in non-PTLD DLBCL, and while several clinical factors have been identified and validated for predicting non-PTLD DLBCL outcomes, the molecular profile of PTLD DLBCL has not yet been characterized. Compartment-specific metabolic reprograming has been described in non-PTLD DLBCL with a lactate uptake metabolic phenotype with high monocarboxylate transporter 1 (MCT1) expression associated with worse outcomes. The aim of our study was to compare the outcomes of PTLD in our transplant center to historic cohorts, as well as study a subgroup of our PTLD DLBCL tumors and compare metabolic profiles with non-PTLD DLBCL. We performed a retrospective single institution study of all adult patients who underwent a SOT between the years 1992-2018, who were later diagnosed with PTLD. All available clinical information was extracted from the patients' medical records. Tumor metabolic markers were studied in a subgroup of PTLD DLBCL and compared to a group of non-PTLD DLBCL. Thirty patients were diagnosed with PTLD following SOT in our center. Median time from SOT to PTLD diagnosis was 62.8 months (IQR 7.6; 134.4), with 37% of patients diagnosed with early PTLD, and 63% with late PTLD. The most common PTLD subtype was DLBCL. Most patients were treated with reduction of their immunosuppression (RIS) including a group who were switched from calcineurin inhibitor (CNI) to mTOR inhibitor based IS, in conjunction with standard anti-lymphoma chemoimmunotherapy. Progression free survival of the PTLD DLBCL cohort was calculated at 86% at 1 year, and 77% at 3 and 5-years, with overall survival of 86% at 1 and 3-years, and 75% at 5 years. Death censored allograft survival in the kidney cohort was 100% at 1 year, and 93% at 3, 5 and 10 years. MCT1 H scores were significantly higher in a subset of the non-PTLD DLBCL patients than in a PTLD DLBCL cohort. Our data is concordant with improved PTLD outcomes in the last 10 years. mTOR inhibitors could be an alternative to CNI as a RIS strategy. Finally, PTLD DLBCL may have a distinct metabolic profile with reduced MCT1 expression compared to non-PTLD DLBCL, but further studies are needed to corroborate our limited cohort findings and to determine if a specific metabolic profile is associated with outcomes.

Successful treatment of polymorphic post-transplant lymphoproliferative disorder after allo-HSCT with reduction of immunosuppression.

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication for recipients of solid organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). In SOT recipients, who previously have a normal immune system that has been immunosuppressed, reduction of immunosuppression (RI) shows favorable outcome. However, in HSCT recipients, who have been profoundly immunosuppressed and for whom the tempo of immune reconstitution cannot be fast enough to eliminate the lymphoproliferative process, RI is ineffective in most patients. Therefore, cases of tumor regression via RI alone are rare in the setting of HSCT. We present a case of 26-year-old female developing a polymorphic B-cell PTLD 4 months after receiving allo-HSCT for T cell lymphoblastic lymphoma. RI alone led to regression of the nasopharyngeal tumor, and no sign or evidence of graft-versus-host disease (GVHD) after RI was observed. The general condition of this patient was quite well just before we submitted our draft. To our knowledge, this is the first case that tumor of PTLD regressed upon RI alone with a favorable prognosis and without any evidence of GVHD and relapse of PTLD after RI therapy in the setting of HSCT, which justify the possible advantage of RI alone for low-risk patients.