Transplantations-assoziierte Lymphoproliferationen

Der Pathologe (Impact Factor: 0.39). 03/2011; 32(2):152-158. DOI: 10.1007/s00292-010-1407-x


Transplantation of solid organs and haematopoietic stem cells requires immunosuppressive drug therapy in order to prevent rejection or graft-versus-host disease. Depending on dosage and type of drug, the risk of developing an Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) is increased. The lesion spectrum ranges from hyperplastic lesions to manifest lymphomas, the latter being classified as monomorphic PTLD. Hyperplastic changes, which are not distinguishable from viral reactions, comprise early or mononucleosis-like lesions. Those with effaced lymph node architecture or extranodal manifestation without a lymphoma-like phenotype are designated polymorphic PTLD. Monomorphic PTLD are either high grade B cell lymphomas, plasma cell neoplasms or Hodgkin lymphomas and only very rarely T cell lymphomas. Low grade B cell lymphomas do not occur. In a subfraction of cases, including even monomorphic PTLD, reduction of immunosuppression alone is sufficient to induce remission of the pathological process.

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    ABSTRACT: Transplantation of solid organs and hematopoietic stem cells is accompanied by profound disturbance of immune function mediated by immunosuppressive drugs or delayed immune reconstitution. Disturbed T cell control of Epstein-Barr virus (EBV)-infected B cells leads to posttransplant lymphoproliferative disorder (PTLD) in up to 10% of patients. Children are at a higher risk because they are more often EBV-naïve before transplantation. Patients with PTLD often present with unspecific symptoms (pain and organ/graft dysfunction). Depending on the onset of PTLD, manifestations vary between mainly nodal (late PTLD) and extranodal sites (early PTLD). Histology, immunohistology, EBER in situ hybridization and molecular pathology are required for diagnosis and subclassification of PTLD. The three major types are early lesions (resembling reactive proliferations in immunocompetent patients), polymorphic PTLD (proliferation of B and T cells with effacement of histoarchitecture) and monomorphic PTLD (presenting as malignant lymphomas, mainly high-grade B cell lymphomas). In a subfraction of cases, including monomorphic PTLD, reduction of immunosuppressive medication alone is sufficient to induce remission. Surgical debulking of tumor mass and anti-CD20-antibody treatment with or without chemotherapy (usually at lower dosages than in immunocompetent patients) constitute the basis of additional therapy.
    No preview · Article · Sep 2013 · Pathobiology
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    ABSTRACT: Patients after solid organ transplantation (SOT) carry a substantially increased risk to develop malignant lymphomas. This is in part due to the immunosuppression required to maintain the function of the organ graft. Depending on the transplanted organ, up to 15% of pediatric transplant recipients acquire posttransplant lymphoproliferative disease (PTLD), and eventually 20% of those succumb to the disease. Early diagnosis of PTLD is often hampered by the unspecific symptoms and the difficult differential diagnosis, which includes atypical infections as well as graft rejection. Treatment of PTLD is limited by the high vulnerability towards antineoplastic chemotherapy in transplanted children. However, new treatment strategies and especially the introduction of the monoclonal anti-CD20 antibody rituximab have dramatically improved outcomes of PTLD. This review discusses risk factors for the development of PTLD in children, summarizes current approaches to therapy, and gives an outlook on developing new treatment modalities like targeted therapy with virus-specific T cells. Finally, monitoring strategies are evaluated.
    Full-text · Article · Sep 2013 · Clinical and Developmental Immunology
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    ABSTRACT: Abdominal complications after thoracic transplantation (Tx) are potentially associated with an increased risk of mortality. We recently reported about the severe outcome after bowel perforation in patients following lung transplantation (LuTx). The aim of the present study was to likewise identify the risk factors with an impact on patient survival following heart transplantation (HTx). A retrospective analysis for the frequency and outcome of abdominal interventions following HTx was performed in 342 patients, and these data thereafter compared to a re-evaluated pool of 1,074 patients following LuTx. All patients were transplanted at Hanover Medical School, Germany, between January 2000 and October 2011. The incidence for abdominal surgery was comparable between patients following HTx (n = 33; 9.6 %) and LuTx (n = 90; 8.4 %). Elective operations were more frequently performed in patients after HTx (8.5 vs. 5.1 %). In contrast, the incidence of emergency interventions was higher after LuTx (5.3 %) than that following HTx (2.3 %). Herewith associated was the mortality observed in these transplant recipients (15.3 and 9.9 % for LuTx and HTx, respectively). Leading diagnosis for emergency surgery was bowel perforation (n = 18, regarding all cases). In 11 of these patients, perforation occurred within the first 6 months after Tx and eight of them died in the course of this complication (one patient after HTx and seven patients after LuTx). Abdominal complications after HTx are less frequently than after LuTx but equally correlate with a high mortality rate. In finding or even reasonable suspicion of an acute abdomen after thoracic Tx, a broad practice for extended diagnostics and a low barrier for an early explorative laparotomy thus are recommended.
    No preview · Article · Apr 2014 · Langenbeck s Archives of Surgery
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