Post-transplantation lymphoproliferative disorder (PTLD) with rectal involvement.

Posttransplant Lymphoproliferative Disorder Following Kidney Transplant

Lymphoproliferative disorders after liver transplantation

Fatal Case of EBV-negative Posttransplant Lymphoproliferative Disorder With Hemophagocytic Lymphohistiocytosis in an Adult Kidney Transplant Recipient.

Lymphoproliferation in children after liver transplantation.

II. Challenges in the management of post-transplant lymphoproliferative disorder.

Primary Nonresponse to Anti‐Cd20 Therapy in Gastrointestinal Posttransplant Lymphoproliferative Disorder

Risk of Post-Transplant Lymphoproliferative Disorders (PTLD) in Solid Organ Transplantation Patients with EBV Viremia

Solid organ transplant recipients are at an increased risk for developing malignant neoplasms. Post transplantation lymphoproliferative disorder (PTLD) is a polyclonal or monoclonal lymphoid proliferation occurs in the severe immunosuppression after solid organ transplantation. Epstein-Barr virus infection is one of the most important risk factors for PTLD, even though 40% of PTLD cases in concurrent series are not Epstein-Barr virus-associated. The overall level of immunosuppression seems to be the most important stimulant of the increased occurrence of PTLD in solid organ transplant recipients. Herein, we report two cases of polymorphic PTLD presenting with isolated gastrointestinal involvement in an Epstein-Barr virus negative in one patient with decead-donor kidney transplantation, 6 months after receiving the transplant, and the others Epstein-Barr, CMV virus and covid 19 positive with decead-donor kidney transplantation, 1 year after transplantation. Although rare, gastrointestinal PTLD can lead to small bowel obstruction or perforation in patients with a history of solid-organ transplantation. However typical symptoms may be indefinable in the immunocompromised setting, clinicians should be careful for underlying PTLD with isolated gastrointestinal involvement. Keywords Kidney transplantation; Small bowl; PTLD

Extranodal involvement of the gastrointestinal tract in post transplant lymphoproliferative disorders: Stomach or small bowel involvement increases mortality risk

INTRODUCTION: Post-transplantation lymphoproliferative disorders (PTLDs) are the second most common neoplasms in adult transplant recipients. Epstein-Barr virus infection in the setting of immunosuppressive therapy is implicated etiologically in most cases. More than half of PTLD cases present with extra-nodal involvement including the GI tract. Few reports have described the endoscopic findings. We present a case of rapidly progressive PTLD involving the GI tract with gross lesions that developed less than 2 months after a macroscopically normal upper and lower endoscopy. CASE DESCRIPTION/METHODS: A 37-year-old female with history of orthotopic heart transplant 3 months prior for transposition of the great arteries was admitted to the hospital with 3 weeks of non-bloody diarrhea. Her immunosuppressive regimen included tacrolimus, mycophenolate and prednisone. Extensive serologic and fecal testing was performed with no evidence of systemic CMV, EBV, HSV (serum PCR), clostridium difficile, or other bacterial intestinal infection. She underwent diagnostic upper and lower endoscopy with no grossly visible lesions. Random colon biopsies demonstrated increased lamina propria eosinophils and eosinophilic crypt abscesses suggestive of drug-effect. A presumptive diagnosis of mycophenolate induced colitis was made. Symptoms resolved however during her hospitalization and she was continued on mycophenolate. She presented 6 weeks later with 3 weeks of recurrent non-bloody diarrhea. Repeat serologic and fecal testing revealed EBV and CMV viremia. CT abdomen and pelvis with IV contrast was unremarkable. Repeat upper and lower endoscopy revealed multiple new ulcerated nodular lesions 1 cm in size (Figures 1 and 2) in the stomach, duodenum, terminal ileum and entire colon. Biopsies showed monomorphic PTLD, diffuse large B-cell type, with EBV positive staining. DISCUSSION: PTLD can be isolated to the gastrointestinal tract in immunocompromised post-transplant patients. Endoscopy with biopsy is required to establish the diagnosis. When there is high suspicion for PTLD, consideration should be given for repeat endoscopy even with recent normal examination as macroscopic and microscopic findings may develop rapidly.

EBV-Positive Primary CNS Lymphomas in Older Patients: Incidence, Characteristics, Tumor Pathology, and Outcomes across a Large Multicenter Cohort

Epstein-Barr virus (EBV)-associated B-cell post-transplantation lymphoproliferative disorder (PTLD) is a severe complication following stem cell transplantation. This is believed to occur as a result of iatrogenic immunosuppression leading to a relaxation of T-cell control of EBV infection and thus allowing viral reactivation and proliferation of EBV-infected B-lymphocytes. In support of this notion, reduction of immunosuppressive therapy may lead to regression of PTLD.We present a case of an 18-year-old male developing a monomorphic B-cell PTLD 2 months after receiving an allogenic stem cell transplant for acute lymphoblastic leukemia. Reduction of immunosuppressive therapy led to regression of lymphadenopathy. Nevertheless, the patient died 3 months afterwards due to extensive graft-vs.-host-disease and sepsis. As a diagnostic lymph node biopsy was performed only after reduction of immunosuppressive therapy, we are able to study the histopathological changes characterizing PTLD regression. We observed extensive apoptosis of blast cells, accompanied by an abundant infiltrate comprising predominantly CD8-positive, Granzyme B-positive T-cells. This observation supports the idea that regression of PTLD is mediated by cytotoxic T-cells and is in keeping with the observation that T-cell depletion, represents a major risk factor for the development of PTLD.

Posttransplant lymphoproliferative disease (PTLD) is a critical complication of hematopoietic stem cell transplantation (HSCT). PTLD is classified into early and late-onset PTLDs. In post-HSCT patients, late-onset PTLD is rare, particularly PTLD after HSCT for Epstein-Barr virus (EBV)-related lymphoproliferative disease. Here, we report the case of a patient diagnosed with late-onset EBV-related hemophagocytic lymphohistiocytosis (HLH), that of PTLD, after HSCT for chronic active EBV infection (CAEBV), that of EBV related lymphoproliferative disease, probably because of EBV reactivation. A 22-year-old woman with abdominal fullness visited our hospital. Blood examination showed pancytopenia with atypical lymphocytes, liver dysfunction, and elevated lactate dehydrogenase level. In contrast, bone marrow aspiration showed slight hemophagocytosis with increased natural-killer cells (NK cells). As serum antibodies against EBV were atypical, we calculated the EBV-DNA level in peripheral blood and this level was significantly high. EBV was infected with NK cells, and EBV's monoclonality in NK cells was confirmed. Thus, the patient was diagnosed with CAEBV. The patient received chemotherapy and cord blood cell transplantation (CBT); CAEBV was well controlled. Approximately 6years from CBT for CAEBV, she visited our hospital because of fever. Blood examination revealed pancytopenia with atypical lymphocytes, liver dysfunction, and elevated lactate dehydrogenase level. In contrast, bone marrow aspiration showed hemophagocytosis with increased B and T cell counts without increased NK cell count. Additionally, serum antibody titers against EBV were atypical, and the EBV-DNA level in the peripheral blood was high. EBV was infected with only B cells, and EBV's monoclonality was confirmed. A more detailed analysis indicated that EBV-specific cytotoxic T lymphocytes were inactive. Therefore, she was diagnosed with late-onset EBV-related HLH. She received extensive treatment, but EBV-related HLH did not improve. Finally, she died about 3 weeks after diagnosis. PTLD, including HLH, is a life-threatening complication after transplantation, including HSCT. To our knowledge, this is the first case of late-onset EBV-related HLH after CBT for CAEBV. Late-onset PTLD has an indolent clinical course, but our patient's disease course was extremely aggressive. Therefore, late-onset EBV-related PTLD may be life-threatening.

INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication occurring in up to 30% of post-transplant patients, usually within the first year; however, recurrent PTLD or development of multiple histologic subtypes is rare.1 Relevant to gastroenterologists, GI tract involvement can occur in up to 25% of cases and present as nonspecific clinical symptoms, abdominal pain, bleeding, or perforation.2 CASE DESCRIPTION/METHODS: An 80-year-old African American male with a past medical history of living-donor kidney transplant presented to clinic to undergo surveillance colonoscopy. Nine months post-transplant, the patient was diagnosed with early PTLD on colonoscopy and treated with 4 cycles of rituximab without evidence of disease on repeat colonoscopy or PET scan. Follow up colonoscopy at 5 years did not show any recurrence of disease and the patient was recommended to undergo his next colonoscopy in another 5 years (10 years following PTLD treatment). Repeat colonoscopy at this time found multiple inflammatory polyps at the ileocecal valve and in the transverse and sigmoid colon. Additionally, the rectosigmoid colon showed evidence of moderate inflammation (Figure 1). Pathology reports indicated polyps of the ileocecal valve were consistent with polymorphic PTLD, whereas the biopsies of the rectosigmoid colon showed monomorphic PTLD (Figure 2). The patient was referred to Oncology and is currently undergoing repeat rituximab therapy for monomorphic PTLD and a dose reduction of immunosuppressants for polymorphic PTLD. DISCUSSION: Importantly, even though rates of PTLD are typically lowest for renal transplants (0.8-2.5%), early and recurrent PTLD is still possible in this population.3 Our patient, despite a previous response to rituximab, demonstrated evidence of rare, recurrent PTLD in addition to multiple pathologic subtypes spread diffusely throughout the colon. In particular, the emergence of monomorphic PTLD carries the worst prognosis with survival rates ranging from 25-60%.5,6 Given the frequency of GI tract involvement, it is essential gastroenterologists maintain high suspicion for PTLD in patients with prior transplantation and have a lower threshold for biopsy, as our case demonstrates advanced disease appearing endoscopically as inflammatory changes. Importantly, this recurrence was found 10 years after initial diagnosis, which signifies the importance of surveillance colonoscopy for early detection, monitoring for recurrence, and establishing disease prognosis in PTLD.

Background: Post-transplantation lymphoproliferative disorders (PTLD) are a rare complication of transplantation, although with the increasing number of transplantations this paradigm is changing. Studies describe a peak in PTLD incidence in year 1 post-transplant, and some describe a second peak after 8–10 years. PTLD incidence beyond the 10th year is not well characterized.1 Early-onset of PTLD is frequently related with induction immunosuppression and is often characterized by EBV positivity. Late PTLD (more than 2 years after transplantation) is related with cumulative immunosuppression2. A large multicentre study revealed that 80 PTLD patients after solid organ transplant, whose the majority (80%) received rituximab-based treatment, had a 3-year overall survival (OS) of 62%.3 Aims: To review the prevalence of PTLD in a kidney and liver transplantation centre, time from transplant to diagnosis and outcome. Methods: Data were retrospectively collected from PTLD patients who underwent liver (LT) and kidney transplant (KT) at our centre between January 1985 and December 2018. KT patients received induction immunosuppression followed by maintenance with glucocorticoids, calcineurin inhibitors (CNI) and antimetabolite agent. LT patients received mainly maintenance monotherapy immunosuppression with CNI. As initial management of all patient with PTLD, immunosuppression was reduced, suspended or switched to mTOR inhibitors. The treatment was chosen according to the best practise at the time of diagnosis. Results: Among 2667 KT patients, 33 (1.2%) had PTLD, 22 were male, with a median age at transplantation of 37 years (range 14–64). Median time from transplant to PTLD diagnosis was 11.9 years (range 0.08–27.67), 29 patients (88%) had late PTLD and 17 (52%) were diagnosed ≥10 years from transplant. The overall OS at 3 years was 49%. Monomorphic PTLD was the most frequent diagnosis (25 patients, 75%): 16 had Diffuse Large B Cell Lymphoma (DLBCL), 3 had high grade lymphoma (HGL), not otherwise specified and the remaining 6 had other diagnosis. Nine of the 19 patients diagnosed with DLBCL/HGL were treated with Rituximab based chemotherapy (R-CT) and their 3-years OS was of 35%. Among 1211 LT patients 9 (0.7%) had PTLD, 7 were male, with a median age at transplantation of 50 years (range 21–60). Median time from transplant to PTLD diagnosis was 4.5 years (range 0.06–17.8). Six (67%) patients were diagnosed with late PTLD, 2 more than 10 years from transplant. Four had monomorphic PTLD, 3 DLBCL and 1 Burkitt Lymphoma, 2 patients were treated with R-CT and 2 with A-CT. The LT patients with PTLD had a 3 years OS of 40%. In respect to all 42 patients, with a median follow-up of 2.2 (range 0.01–20.5) years the OS at 3 years is 50%. Summary/Conclusion: We performed an analysis of the PTLD incidence in KT and LT patients in a single centre. Given the retrospective nature and the large period of data collection of this study, our incidence may be underestimated. We observed a higher incidence of PTLD in KT patients compared to LT, which is according to literature. Of those, more than half were diagnosed at least 10 years from transplantation, suggesting that maintenance immunosuppression might be the main reason for PTLD is this cohort. Patients diagnosed with DLBCL/HGL and treated with R-CT had a 3-years OS of 35%, representing a poorer outcome than what is described in literature3.