Epstein-Barr virus positive post-transplant lymphoproliferative disorder with significantly decreased T-cell chimerism early after transplantation:A case report

BACKGROUND Post-transplant lymphoproliferative disorder(PTLD)is a rare but highly fatal complication occurring after allogeneic hematopoietic cell transplantation(allo-HCT)or solid organ transplantation(SOT).Unlike SOT,PTLD after allo-HCT usually originates from the donor and is rarely accompanied by a loss of donor chimerism.CASE SUMMARY We report a case of Epstein-Barr virus positive PTLD manifesting as diffuse large B-cell lymphoma(DLBCL)with significantly decreased T-cell chimerism early after allo-HCT.A 30-year-old patient with acute myeloid leukemia underwent unrelated allo-HCT after first complete remission.Nearly 3 mo after transplantation,the patient developed cervical lymph node enlargement and gastric lesions,both of which were pathologically suggestive of DLBCL.Meanwhile,the patient experienced a significant and persistent decrease in T-cell chimerism.A partial remission was achieved after chemotherapy with single agent rituximab and subsequent R-CHOP combined chemotherapy.CONCLUSION The loss of T-cell chimerism and the concomitant T-cell insufficiency may be the cause of PTLD in this patient.

Post-transplant lymphoproliferative disorder after liver transplantation: Incidence, long-term survival and impact of serum tacrolimus level

To investigate incidence and survival of post-transplant lymphoproliferative disorder (PTLD) patients after liver transplantation.METHODSA cross-sectional survey was conducted among patients who underwent liver transplantation at Shiraz Transplant Center (Shiraz, Iran) between August 2004 and March 2015. Clinical and laboratory data of patients were collected using a data gathering form.RESULTSThere were 40 cases of PTLD in the pediatric age group and 13 cases in the adult group. The incidence of PTLD was 6.25% in pediatric patients and 1.18% in adult liver transplant recipients. The post-PTLD survival of patients at 6 mo was 75.1% ± 6%, at 1 year was 68.9% ± 6.5% and at 5 years was 39.2% ± 14.2%. Higher serum tacrolimus level was associated with lower post-PTLD survival in pediatric patients (OR = 1.07, 95%CI: 1.006-1.15, P = 0.032). A serum tacrolimus level over 11.1 ng/mL was predictive of post PTLD survival (sensitivity = 90%, specificity = 52%, area under the curve = 0.738, P = 0.035).CONCLUSIONIncidence of PTLD in our liver transplant patients is comparable to other centers. Transplant physicians may consider adjustment of tacrolimus dose to maintain its serum level below this cutoff point.

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.

Epstein-Barr virus-associated monomorphic post-transplant lymphoproliferative disorder after pediatric kidney transplantation: A case report

BACKGROUND Post-transplant lymphoproliferative disease(PTLD)is the most common malignant tumor that occurs after kidney transplantation in children,and is associated with Epstein-Barr virus(EBV).CASE SUMMARY We report a case of PTLD that occurred in a 17-year-old female patient at 5 mo post-transplant.The first symptom was abdominal pain accompanied by fever,nausea,and vomiting.EBV-associated monomorphic PTLD with multiple abdominal nodules was diagnosed by pathology,clinical manifestations,imaging results,and the presence of EB-DNA.After successful treatment with rituximab,the abdominal nodules in the spleen and liver disappeared.CONCLUSION Early pathological biopsy to confirm the diagnosis is critical to treatment and prognosis.Reducing immunosuppression and rituximab therapy are effective methods for treating PTLD,but need to be initiated as early as possible.

Coexistent Kaposi sarcoma and post-transplant lymphoproliferative disorder in the same lymph nodes after pediatric liver transplantation:A case report

BACKGROUND Kaposi sarcoma and post-transplant lymphoproliferative disorder have been occasionally reported in post-liver transplant patients.However,the simultaneous occurrence of these two diseases in the same lymph nodes is very rare.CASE SUMMARY We report the case of a 19-mo-old boy,who presented with intermittent fever and enlarged cervical lymph nodes after liver transplantation.Six cervical lymph nodes were biopsied,and the histopathological examinations revealed multifocal hyperplasia of spindle cells around small blood vessels,extravasated erythrocytes,and heavy infiltration of plasma cells in the cortex and medulla of the lymph nodes.The immunohistochemical analyses of spindle cells revealed positive expression of CD34,CD31,erythroblast transformation-specific-related gene,friend leukemia integration 1,and human herpesvirus-8.The lymphoproliferative lesions expressed CD38,CD138,and multiple myeloma 1.Epstein-Barr encoded RNA in situ hybridization demonstrated Epstein-Barr virus-positive lymphoid cells.Finally,we diagnosed the coexistence of Kaposi sarcoma and post-transplant lymphoproliferative disorder(plasmacytic hyperplasia)in the same lymph nodes.Treatment strategy included anti-CD20 monoclonal antibody(rituximab)and discontinuation of the immunosuppressant therapies.Lymph node biopsies during follow-up examinations revealed lymphoid hyperplasia.CONCLUSION The rare coexistence of Kaposi sarcoma and post-transplant lymphoproliferative disorder in the same lymph nodes post-liver transplantation possibly associates with immunodeficiency and Epstein-Barr virus and human herpesvirus-8 coinfection.

Isolated peritoneal lymphomatosis defined as post-transplant lymphoproliferative disorder after a liver transplant: A case report

BACKGROUND Post-transplant lymphoproliferative disorder(PTLD) is a fatal complication of solid organ transplantation or allogenic hematopoietic stem cell transplantation that is associated with immunosuppressive therapy. Potential manifestations are diverse, ranging from reactive lymphoid hyperplasia to high-grade lymphoma.PTLD is usually of B-cell origin and associated with Epstein-Barr virus(EBV)infection. Herein, we describe a case of PTLD involving the peritoneal omentum.There has been only case of PTLD as a diffuse large B-cell lymphoma(DLBCL) in the peritoneum.CASE SUMMARY The patient was a 62-year-old man who had been receiving immunosuppressive therapy with tacrolimus since undergoing a liver transplant 15 years prior. He reported that he had experienced abdominal discomfort and anorexia 1 month prior to the current admission. Abdominal pelvic computed tomography(CT)revealed peritoneal and omental mass-like lesions without bowel obstruction.Ultrasonography-guided biopsy was performed, and he was histologically diagnosed with EBV-negative DLBCL. Positron emission tomography(PET)-CT depicted peritoneum and omentum involvement only, without any lymphadenopathy or organ masses, including in the gastrointestinal tract. Six cycles of chemotherapy with a "R-CHOP" regimen(rituximab-cyclophosphamide, doxorubicin, vincristine, prednisolone) were administered,and PET-CT performed thereafter indicated complete remission.CONCLUSION This is the first report of isolated peritoneal lymphomatosis defined as PTLD in a liver transplant recipient.

Gastrointestinal tract post-transplant lymphoproliferative disorder after liver transplantation

To the Editor:Post-transplant lymphoproliferative disorder（PTLD）is a rare and potentially fatal complication occurring after all types of solid organ transplantation.;PTLD accounts for 20%of all de novo post-transplant tumors.;The most important risk factors for PTLD are prolonged intense immunosuppression and Epstein-Barr virus（EBV）

Post-transplant lymphoproliferative disorder treated with rituximab:case report

Post-transplant lymphoproliferative disorder （PTLD）, a rare disease, is characterized by an abnormal proliferation of lymphoid cells after solid organ transplantation. This complication is usually caused by the immunosuppressive therapy following transplantation Though the techniques of early detection and diagnosis of the disease are well established, treatment is not so straightforward and poses a real challenge. At this time, options include anti-viral therapy, cytotoxic chemotherapy, cellular immunotherapy, and reduction of immunosuppression. But the effects of these therapies are not satisfying. Rituximab, a chimeric monoclonal anti-CD20 antibody used for the treatment of B cell lymphoma with a good effect, is rarely, especially in combination with chemotherapy, used for PTLD. In this report, we describe a case of PTLD treated with rituximab and chemotherapy resulting in complete remission.

Post-transplantation lymphoproliferative disorders:Current concepts and future therapeutic approaches

Transplant recipients are vulnerable to a higher risk of malignancy after solid organ transplantation and allogeneic hematopoietic stem-cell transplant.Posttransplant lymphoproliferative disorders(PTLD)include a wide spectrum of diseases ranging from benign proliferation of lymphoid tissues to frank malignancy with aggressive behavior.Two main risk factors of PTLD are:Firstly,the cumulative immunosuppressive burden,and secondly,the oncogenic impact of the Epstein-Barr virus.The latter is a key pathognomonic driver of PTLD evolution.Over the last two decades,a considerable progress has been made in diagnosis and therapy of PTLD.The treatment of PTLD includes reduction of immunosuppression,rituximab therapy,either isolated or in combination with other chemotherapeutic agents,adoptive therapy,surgical intervention,antiviral therapy and radiotherapy.In this review we shall discuss the prevalence,clinical clues,prophylactic measures as well as the current and future therapeutic strategies of this devastating disorder.

Recent insights in the pathogenesis of post-transplantation lymphoproliferative disorders

Post-transplant lymphoproliferative disorder(PTLD) is an aggressive complication of solid organ and hematopoietic stem cell transplantation that arises in up to 20% of transplant recipients. Infection or reactivation of the Epstein-Barr virus(EBV), a ubiquitous human herpesvirus, in combination with chronic immunosuppression are considered as the main predisposing factors, however insight in PTLD biology is fragmentary. The study of PTLD is complicated by its morphological heterogeneity and the lack of prospective trials, which also impede treatment optimization. Furthermore, the broad spectrum of underlying disorders and the graft type represent important confounding factors. PTLD encompasses different malignant subtypes that resemble histologically similar lymphomas in the general population. Post-transplant diffuse large B-cell lymphoma(PT-DLBCL), Burkitt lymphoma(PTBL) and plasmablastic lymphoma(PT-PBL) occur most frequently. However, in many studies various EBV+ and EBV- PTLD subtypes are pooled, complicating the interpretation of the results. In this review, studies of the gene expression pattern, the microenvironment and the genetic profile of PT-DLBCL, PT-BL and PT-PBL are summarized to better understand the mechanisms underlying post-transplantation lymphomagenesis. Based on the available findings we propose stratification of PTLD according to the histological subtype and the EBV status to facilitate the interpretation of future studies and the establishment of clinical trials.

Epstein-Barr virus-associated post-transplant lymphoproliferative disorders:beyond chemotherapy treatment

Post-transplant lymphoproliferative disorder(PTLD)is a rare but life-threatening complication of both allogeneic solid organ(SOT)and hematopoietic cell transplantation(HCT).The histology of PTLD ranges from benign polyclonal lymphoproliferation to a lesion indistinguishable from classic monoclonal lymphoma.Most commonly,PTLDs are Epstein-Barr virus(EBV)positive and result from loss of immune surveillance over EBV.Treatment for PTLD differs from the treatment for typical non-Hodgkin lymphoma because prognostic factors are different,resistance to treatment is unique,and there are specific concerns for organ toxicity.While recipients of HCT have a limited time during which they are at risk for this complication,recipients of SOT have a lifelong requirement for immunosuppression,so approaches that limit compromising or help restore immune surveillance are of high interest.Furthermore,while EBV-positive and EBV-negative PTLDs are not intrinsically resistant to chemotherapy,the poor tolerance of chemotherapy in the post-transplant setting makes it essential to minimize potential treatment-related toxicities and explore alternative treatment algorithms.Therefore,reduced-toxicity approaches such as single-agent CD20 monoclonal antibodies or bortezomib,reduced dosing of standard chemotherapeutic agents,and non-chemotherapy-based approaches such as cytotoxic T cells have all been explored.Here,we review the chemotherapy and non-chemotherapy treatment landscape for PTLD.

EBV-Associated Post-Transplantation B-Cell Lymphoproliferative Disorder in Patient after Allogenic Stem Cell Transplantation

Epstein-Barr virus (EBV)-associated B-cell post-transplantation lymphoproliferative disorder (PTLD) is a severe complication following solid-organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (HSCT). We present a case of a 15-year-old male developing a monomorphic B-cell PTLD after receiving an allogenic stem cell transplant for acute acute myeloid leukemia. A diagnostic lymph node biopsy revealed monomorphic type, B cell phenotype, associated with Epstein-Barr virus, consistent with post-transplant lymphoproliferative disorder (PTLD). The morbidity and mortality of PTLD are high, and there is no standard protocol for treatment of PTLD. To prevent the occurrence of PTLD and early intervention are important for the prognosis of patients.

Efficacy of rituximab-containing regimens on post-transplantation lymphoproliferative disorder following haploidentical hematopoietic stem cell transplantation:a report of 3 cases

Objective To evaluate the efficacy of rituximab-containing regimens on post - transplantation lympho-proliferative disorder ( PTLD ) following haploidentical hematopoietic stem cell transplantation ( HSCT) . Methods The clinical data of 3 cases of PTLD after haploidentical HSCT were analyzed retrospectively. Time

Epstein-Barr virus-positive post-transplant lymphoproliferative disordepresenting as hematochezia and enterobrosis in renal transplant recipients in China: A report of two cases

BACKGROUND Post-transplant lymphoproliferative disorder(PTLD) is a rare severe complication after renal transplantation, with an incidence of approximately 0.3%-2.0% in patients undergoing renal transplantation. The clinical manifestations of PTLD are often nonspecific, leading to tremendous challenges in the clinical diagnosis and treatment of PTLD.CASE SUMMARY We report two Epstein-Barr virus(EBV)-positive PTLD cases whose main clinical manifestations were digestive tract symptoms. Both of them admitted to our hospital because of extranodal infiltration symptoms and we did not suspect of PTLD until the pathology confirmation. Luckily, they responded well to the treatment of rituximab. We also discuss the virological monitoring, clinical characteristics, diagnosis, and treatment of PTLD.CONCLUSION PTLD is a deceptive disease and difficult to diagnose. Once patients are confirmed with PTLD, immune suppressant dosage should be immediately reduced and rituximab should be used as first-line therapy.

Impact of EBV infection and immune function assay for lymphoproliferative disorder in pediatric patients after liver transplantation: A single-center experience

Background:Post-transplant lymphoproliferative disorder(PTLD)is a lethal complication after pediatric liver transplantation,but information regarding risk factors for the development of PTLD remains unclear.This study was to identify characteristics and risk factors of PTLD.Methods:A total of 705 pediatric patients who underwent liver transplantation between January 2017 and October 2018 were studied.Impact of clinical characteristics and Epstein-Barr virus(EBV)infection on the development of PTLD was evaluated.In addition,ImmuKnow assay was adopted in partial patients to analyze the immune status.Results:Twenty-five(3.5%)patients suffered from PLTD with a median time of 6 months(3–14 months)after transplantation.Extremely high tacrolimus(TAC)level was found in 2 fatal cases at PTLD onset.EBV infection was found in 468(66.4%)patients.A higher peak EBV DNA loads(>9590 copies/mL)within 3 months was a significant indicator for the onset of PTLD.In addition,the ImmuKnow assay demonstrated that overall immune response was significantly lower in patients with EBV infection and PTLD(P<0.0001).The cumulative incidence of PTLD was also higher in patients with lower ATP value(≤187 ng/mL,P<0.05).Conclusions:A careful monitoring of EBV DNA loads and tacrolimus concentration might be supportive in prevention of PTLD in pediatric patients after liver transplantation.In addition,application of the ImmuKnow assay may provide guidance in reducing immunosuppressive agents in treatment of PTLD.

Hepatitis C virus-related lymphoproliferative disorders:An overview

Hepatitis C virus （HCV） is a global health problem affecting 3% of the world＇s population （about 180 million） and a cause of both hepatic and extrahepatic diseases. B-cell lymphoproUferative disorders, whose prototype is mixed cryoglobulinemia, represent the most closely related as well as the most investigated HCV- related extrahepatic disorder. The association between extrahepatic （lymphoma） as well as hepatic malignancies （hepatocellular carcinoma） has justified the inclusion of HCV among human cancer viruses. HCV-associated manifestations also include porphyria cutanea tarda, lichen planus, nephropathies, thyreopathies, sicca syndrome, idiopathic pulmonary fibrosis, diabetes, chronic polyarthritis, sexual dysfunctions, cardiopathy/ atherosclerosis, and psychopathological disorders. A pathogenetic link between HCV virus and some lymphoproliferative disorders was confirmed by their responsiveness to antiviral therapy, which is now considered the first choice treatment. The aim of the present paper is to provide an overview of extrahepatic manifestations of HCV infection with particular attention to B-cell lymphoproliferative disorders. Available pathogenetic hypotheses and suggestions about the most appropriate, currently available, therapeutic approaches will also be discussed.

Persistent Epstein-Barr viral load in Epstein-Barr viral na?ve pediatric heart transplant recipients:Risk of late-onset post-transplant lymphoproliferative disease

AIM To examine the risk of late-onset post-transplant lymphoproliferative disorder(PTLD) in the presence of persisting high Epstein-Barr virus(EBV) in EBV na?ve pediatric heart transplant(HT) recipients. METHODS A retrospective review of the medical records of the 145 pediatric HT recipients who had serial EBV viral load monitoring at our center was performed. We defined EBV naive patients whose EBV serology either IgM or IgG in the blood were negative at the time of HT and excluded passive transmission from mother to child in subjects less than 6 mo of age. RESULTS PTLD was diagnosed in 8 out of 145 patients(5.5%); 6/91(6.5%) in those who were EBV seropositive and 2/54(3.7%) in the EBV na?ve group at the time of HT(P = 0.71). We found 32/145(22%) patients with persistently high EBV load during continuing follow-up; 20/91(22%) in EBV seropositive group vs 12/54(22%) in EBV na?ve group(P = 0.97). There was no significant association between pre-HT serostatus and EBV load after transplant(P > 0.05). In the EBV seropositive group, PTLD was diagnosed in 15%(3/20) of patients with high EBV vs 4.2%(3/71) of patients with low or undetectable EBV load(P = 0.14) whereas in EBV na?ve patients 8.3%(1/12) of those withhigh EBV load and 2.3%(1/42) with low or undetectable EBV load(P = 0.41). There was a highly significant association between occurrence of PTLD in those with high EBV load and duration of follow up(4.3 ± 3.9 years) after HT by Cochran-Armitage test for the entire cohort(P = 0.005). At least one episode of acute rejection occurred in 72%(23/32) of patients with high EBV vs 36%(41/113) patients with low or undetectable EBV after HT(P < 0.05). CONCLUSION There is an association between persistently high EBV load during post-HT follow up and the occurrence of late-onset PTLD in pediatric HT recipients irrespective of serostatus at the time of transplant. The occurrence of allograft rejection increased in patients with high EBV load presumably due to reduction in immunosuppression.

STUDY ON CELL ORIGIN OF MALIGNANT LYMPHOPROLIFERATIVE DISORDERS WITH POLYMERASE CHAIN REACTION

Genotype of IgH, TCRγ and TCR δ gene rearrangement in 42 cases of malignant lymphoproliferative disorders were studied by using polymerase chain reaction (PCR) technique. The results suggested that among the 23 cases, in which malignant cells expressed B-lineage cell surface markers, 20 showed IgH gene rearrangement and 11 had TCRγ gene rearrangement and / or TCRδ gene deletion. All the 11 cases expressed T-lineage cell differentiation antigens were found to have TCRγand TCRδ gene rearrangement or deletion and only one had IgH gene rearrangement. Double rearrangements of IgH and TCRγ genes were detected in all the 3 cases of T and B double-phenotype ALL. In the cases malignant cells did not express any lineage specific antigens while 4/5 had TCRγ gene rearrangement but all failed in IgH gene rearrangement. The relation of cellular differentiation origin and rearrangement of antigen receptor genes with clinical manifestations was discussed.

Effects of oncological treatments on semen quality in patients with testicular neoplasia or lymphoproliferative disorders

Pretherapy sperm cryopreservation in young men is currently included in good clinical practice guidelines for cancer patients. The aim of this paper is to outline the effects of different oncological treatments on semen quality in patients with testicular neoplasia or lymphoprol iferative disorders, based on an 8-year experience of the Cryopreservation Centre of a large public hospital. Two hundred and sixty-one patients with testicular neoplasia and 219 patients with lymphoproliferative disorders who underwent chemotherapy and/or radiotherapy and pretherapy semen cryopreservation were evaluated. Sperm and hormonal parameters （follicle-stimulating hormone （FSH）, luteinizing hormone （LH）, testosterone, inhibin B levels） were assessed prior to and 6, 12, 18, 24 and 36 months after the end of cancer treatment. At the time of sperm collection, baseline FSH level and sperm concentration were impaired to a greater extent in patients with malignant testicular neoplasias than in patients with lymphoproliferative disorders. Toxic effects on spermatogenesis were still evident at 6 and 12 months after the end of cancer therapies, while an improvement of seminal parameters was observed after 18 months. In conclusion, an overall increase in sperm concentration was recorded about 18 months after the end of cancer treatments in the majority of patients, even if it was not possible to predict the evolution of each single case ＇a priori＇. For this reason, pretherapy semen cryopreservation should be considered in all young cancer patients.

Immunophenotype and Ultrastructure of B-cell Lymphoproliferative Disorder with Cytoplasmic Projection

To identify the knowledge of rare lymphoproliferative disorder, the clinical and biological features of three kinds of lymphoproliferative disorders with cytoplasmic projections were compared The clinical manifestations, ultrastructure and immunophenotype were analyzed The results showed that hairy cell leukemia (HCL), splenic lymphoma with villous lymphocyte (SLVL) and hairy cell leukemia-variant (HCL-V) had some common characters including splenomegaly, peripheral blood and bone marrow infiltration by villous lymphocyte and B lymphocyte immunophenotype; but these three disorders had specific features respectively It was concluded that overall analysis of clinical and laboratory features might be contributive to the differential diagnosis of these three disorders