Form Of Post-transplant Lymphoproliferative Disorder Research Articles

Burkitt lymphoma after solid-organ transplant: Treatment and outcomes in the paediatric PTLD collaborative.

Burkitt lymphoma arising in paediatric post-solid-organ transplantation-Burkitt lymphoma (PSOT-BL) is a clinically aggressive malignancy and a rare form of post-transplant lymphoproliferative disorder (PTLD). We evaluated 35 patients diagnosed with PSOT-BL at 14 paediatric medical centres in the United States. Median age at organ transplantation was 2.0 years (range: 0.1-14) and age at PSOT-BL diagnosis was 8.0 years (range: 1-17). All but one patient had late onset of PSOT-BL (≥2 years post-transplant), with a median interval from transplant to PSOT-BL diagnosis of 4.0 years (range: 0.4-12). Heart (n= 18 [51.4%]) and liver (n= 13 [37.1%]) were the most frequently transplanted organs. No patients had loss of graft or treatment-related mortality. A variety of treatment regimens were used, led by intensive Burkitt lymphoma-specific French-American-British/Lymphomes Malins B (FAB/LMB), n= 13 (37.1%), and a low-intensity regimen consisting of cyclophosphamide, prednisone and rituximab (CPR) n= 12 (34.3%). Median follow-up was 6.7 years (range: 0.5-17). Three-year event-free and overall survival were 66.2% and 88.0%, respectively. Outcomes of PSOT-BL patients receiving BL-specific intensive regimens are comparable to reported BL outcomes in immunocompetent children. Multi-institutional collaboration is feasible and provides the basis of prospective data collection to determine the optimal treatment regimen for PSOT-BL.

Amyloidosis Diagnosed in Solid Organ Transplant Recipients

Development of amyloidosis post solid-organ transplantation has not been reported, although plasma cell neoplasms are a rare form of posttransplant lymphoproliferative disorder, which could be complicated by light chain amyloidosis (AL) amyloidosis. We searched our database of 5112 patients seen between 1994 and 2018 with a diagnosis of amyloidosis post solid-organ transplant. Patients were excluded if the amyloid diagnosis preceded the transplant date. The indication and type of organ transplant were recorded in addition to the amyloidosis type, organs involved, treatment given, and survival. Thirty patients were identified. The median age at diagnosis with amyloidosis was 52 years (range 33-77). The median time from transplantation to diagnosis was 10.5 years (0.58-36). The grafts were kidney (N = 25, 83.3%), liver (N = 2, 6.7%), heart (N = 2, 6.7%), and combined heart, lung, and kidney (N = 1, 3.3%). The type of amyloidosis was systemic AL (N = 14, 47%), serum amyloid A amyloidosis (AA) (N = 11, 37%), localized AL (N = 3, 10%), wild-type transthyretin amyloidosis (ATTR) (N = 1, 3.3%), and amyloid of uncertain type (N = 1, 3.3%). Renal graft dysfunction was seen in 11 of 25 (44%) cases. Median graft survival was 185 months (96-269), and median survival from diagnosis with amyloidosis was 45 months (2-89); median survival by amyloidosis type was localized AL: 64 months (20-67), systemic AL: 23.5 months (0-95), ATTR amyloidosis: 17 months, and AA, 15 months (0-77). This series is the first description of amyloidosis post solid-organ transplant; 30 cases among 5112 amyloid patients >24 years suggests that amyloidosis may occur post solid-organ transplantation with an overall poor survival.

Long-Term Evaluation of Post-transplant Lymphoproliferative Disorders in Paediatric Heart Transplantation in Sao Paulo, Brazil.

We sought to better define the demographics and characteristics of post-transplant lymphoproliferative disorders (PTLD) in a cohort of paediatric OHT patients from a developing country. Data were collected from the Heart Institute, Sao Paulo, for all paediatric OHT recipients from October 1992 to October 2018. Group differences between the PTLD and non-PTLD cohorts were assessed by Fisher exact and Mann-Whitney U tests. Kaplan-Meier curves analysed the survival in each group. Data were reviewed for 202 paediatric OHT recipients. Overall 1-, 5- and 10-year survival for the entire cohort was 76.5%, 68.3% and 62.9%; 24 patients (11.9%) developed PTLD at a median 3.1years (IQR 0.8-9.0) after OHT. Cases were evenly spread over the follow-up period, with PTLD diagnosed in 9.8% (n = 137) of patients who were alive at 3years, 15.3% (n = 78) of patients who were alive at 5years and 29.3% (n = 41) of patients who were alive at 10years. The commonest form of PTLD was diffuse large B cell lymphoma (n = 9), and most patients received rituximab with immunosuppression and chemotherapy as treatment (n = 15). We identified no increased risk in mortality amongst the PTLD vs. non-PTLD cohorts in multivariate analysis (P = 0.365). PTLD after paediatric OHT had acceptable outcomes. However, risk factors for PTLD were not identified and warrant further investigation.

Expanding the Spectrum of EBV-positive Marginal Zone Lymphomas: A Lesion Associated With Diverse Immunodeficiency Settings.

Traditionally low-grade B-cell lymphomas have been excluded from the category of monomorphic posttransplant lymphoproliferative disorders. However, recent reports identified Epstein-Barr virus-positive (EBV) extranodal marginal zone lymphomas (MZL), almost exclusively seen in the posttransplant setting. Some reported cases responded to reduced immunosuppression, suggesting that they should be considered as a form of posttransplant lymphoproliferative disorders. We identified 10 cases of EBV MZL, 9 in extranodal sites and 1 presenting in lymph node. Two cases arose following solid organ transplantation, but other settings included iatrogenic immunosuppression for rheumatoid arthritis (2); prior chemotherapy (2); congenital immune deficiency (1); and increased age (3), as the only potential cause of immune dysfunction. There were 4 males and 6 females; age range 18 to 86. The atypical plasmacytoid and/or monocytoid B cells were positive for EBV in all cases, with either latency I or II in all cases tested. Monotypic light chain expression was shown in all with 6 cases positive for IgG, and 2 for IgM, undetermined in 2. Clonal immunoglobulin gene rearrangement was positive in all cases with successful amplification. MYD88 L265P was wild type in the 6 cases tested. We show that EBV MZLs can arise in a variety of clinical settings, and are most often extranodal. Treatment varied, but most patients had clinically indolent disease with response to reduction of immune suppression, or immunochemotherapy.

Development of Hodgkin's Lymphoma-Like Post-Transplant Lymphoproliferative Disorder after Tandem Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma

Post Transplant Lymphoproliferative Disorders (PTLDs) are serious complication after solid organ or Hematopoietic Stem Cell Transplantation (HSCT). Hodgkin's Lymphoma (HL)-like PTLD is grouped with HL type PTLD in the World Health Organization. HL type PTLD is the rarest form of PTLD.

Long-Term Maintenance Therapy for Post–Cardiac Transplant Monoclonal Lymphoproliferative Disorder: Caveat Mammalian Target of Rapamycin

A 53-year-old Caucasian male suffering from idiopathic dilated cardiomyopathy underwent cardiac transplantation. Fifty-seven days following transplant, he developed posttransplant lymphoproliferative disorder (PTLD), which was Epstein-Barr virus positive. The initial episode of PTLD was treated with a dose reduction in cyclosporine (CsA) and a 4-week course of rituximab. Subsequent biopsies showed resolution of PTLD. One year posttreatment, his evaluation revealed severe cardiac allograft vasculopathy (CAV). The patient was switched to sirolimus-based immunosuppression regimen with gradual up-titration of sirolimus in combination with complete withdrawal of previously administered Calcineurin-based immunosuppression approach. The switchover was carried out over a 6-week period. In the following 3 years, there was CAV regression as well as PTLD remission, without any significant episode of rejection. Despite frequent relapses with this form of PTLD, the patient remains in remission, 8 years posttransplantation. In summary, sirolimus has been demonstrated to attenuate the progression of CAV, and this case report illustrates that regression of CAV is possible. In addition to preventing rejection, mammalian target of rapamycin inhibitors directly suppress signaling pathways leading to PTLD and may be effective monotherapy for preventing rejection and suppressing PTLD.

Post‐transplant hepatosplenic T‐cell lymphoma successfully treated with hyperCVAD regimen

Hepatosplenic T-cell lymphoma (HSTL) is an aggressive lymphoma. In post-transplant immunosuppressed patients, HSTL is usually rapidly fatal. We report successful treatment of post-transplant HSTL in a 50-year-old renal allograft recipient by reducing immunosuppression and using intensive chemotherapy consisting of alternating cycles of HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and MTX/HiDAC (methotrexate, Ara-C). Remission is ongoing at 8+ years. Literature review identified another 20 cases of HSTL in solid organ transplant recipients: median survival was 4 months; no other patients survived beyond 12 months. Bone marrow involvement was universal, but changes were often subtle: 6 of 12 cases had nondiagnostic examinations earlier on. High index of suspicion may lead to more timely diagnosis of this uncommon form of post-transplant lymphoproliferative disorder, and treatment with intensive chemotherapy such as HyperCVAD may be curative.

Clonal T-Large Granular Lymphocyte Proliferation in Solid Organ Transplant Recipients

Large granular lymphocytic (LGL) leukemia is a rare disorder, usually caused by clonal proliferation of CD3+ CD57+ T-LGL cells. T-cell clonality is confirmed by rearrangements of the T-cell receptor (TCR) gene. Characteristic features of T-LGL leukemia include neutropenia, anemia, and constitutional symptoms such as fatigue. Many solid organ transplant recipients experience similar symptoms and have neutropenia and anemia often attributed to immunosuppressive therapy. The purpose of this study was to determine the prevalence of T-LGL proliferation in solid organ transplant recipients and demonstrate its association with leukopenia and anemia. Twenty-three cardiac and renal transplant patients were evaluated by peripheral smear examination, flow cytometry, and TCR gene rearrangement study by polymerase chain reaction. Ten of 14 (71%) cardiac transplant patients and 4 of 9 (44%) renal transplant patients, without evidence of either allograft rejection or a viral syndrome, were found to have clonal expansion of T-LGL cells. Constitutional symptoms were present in 30% of these patients. Anemia of <10 g/dL was seen in 75% of renal transplant and 10% of cardiac transplant patients. None of these patients had significant neutropenia defined as absolute neutrophil count of 1500 μ/L. Most of the patients did not require any specific therapeutic intervention. Although TCR gene rearrangement is considered a hallmark of T-LGL leukemia, we believe that this monoclonality is not a true form of posttransplant lymphoproliferative disorder. Constant antigenic stimulus from the allograft may be the underlying etiology of clonal expansion and may contribute to cytopenias and fatigue seen in transplant patients.

A case of fulminant post‐transplant lymphoproliferative disorder and septicemia

The fulminant form of post-transplant lymphoproliferative disorder (PTLD) is very uncommon and occurs in approximately 1% of PTLD patients. Approximately 85% of these lesions are of B-cell origin, and most of them are associated with Epstein-Barr virus infection. Fulminant PTLD is frequently associated with a systemic inflammatory response syndrome, and may be difficult to differentiate from septicemia. We describe the case of a 59-yr-old man who suffered from prolonged septicemia in the immediate post-transplant period, and presented again four months after cardiac transplantation with fever, painful liver edge and gastrointestinal bleeding. The diagnosis of fulminant PTLD with advanced multiorgan infiltration by a diffuse large-cell lymphoma of B-cell phenotype was made. During treatment with rituximab, the patient died from Enterococcus faecium septicemia. The sequence of septicemia, PTLD and, finally again, septicemia is an unusual challenge and urges for an aggressive diagnostic approach, where markers like procalcitonin may aid in the discrimination of fulminant PTLD from septicemia.

Plasmacytic hyperplasia—the early form of posttransplant lymphoproliferative disorder—with atypical morphology and clinical course in patient after liver transplantation: a case report

This case report describes an early lesion of posttransplant lymphoproliferative disorder (PLTD)—plasmacytic hyperplasia with atypical morphology. The 54-year-old patient was 4 months after liver transplantation due to alcoholic cirrhosis. The postoperative course had been uneventful without graft rejection episodes. Primary immunosuppressive therapy included tacrolimus and prednisone. On admission to the hospital the patient showed rapidly increasing jaundice, hepatomegaly, anemia, thrombocytopenia, and significant leukocytosis. A biopsy suggested generalized infection. Acute Epstein-Barr virus (EBV) infection was confirmed using serological methods. Despite treatment the patient died. On autopsy we found features of generalized infection. Histological examination of the enlarged lymph nodes showed plasmacytic hyperplasia despite lymph node atrophy. Plasmacytic hyperplasia, an early lesion of PTLD despite usually a good prognosis with multifactor therapy may display a rapid course that leads to death through intensified immunosuppression. In accordance with other reports we confirmed reactivation of EBV infection as the probable cause of plasmacytic hyperplasia. The lymph node morphology of plasmacytic hyperplasia may be atypical with atrophy of lymphoid components accompanying plasma cell proliferation.

Multiple myeloma after cardiac transplantation: An unusual form of posttransplant lymphoproliferative disorder

Published reports of posttransplant myeloma are extremely uncommon (three cases); to the best of our knowledge there have been no reported cases in cardiac transplant recipients. We are also unaware of any report of Epstein-Barr virus (EBV) genome studies in posttransplant myeloma. We report here the case of a 48-year-old man who developed multiple myeloma 1.5 years after cardiac transplantation. The results of a serum analysis were consistent with past EBV infection. Biopsy of a skull lesion showed a monomorphous population of malignant immature plasma cells that showed monotypic cytoplasmic staining with antibodies to lambda light chains. A monoclonal immunoglobulin heavy chain gene rearrangement was detected by polymerase chain reaction (PCR). Both EBER-1 in situ hybridization and EBNA-1 PCR were negative for the EBV genome. Cyclosporin withdrawal was followed by transient clinical and biological improvement, but the tumor later progressed and eventually stabilized in response to treatment with dexamethasone alone. This case illustrates that posttransplant lymphoproliferative disorders (PTLPDs) encompass not only EBV-positive but also EBV-negative cases and not only lymphomas but also myelomas.