{"entity":{"id":"post-transplant-lymphoproliferative-disorder","kind":"cancer","name":"Post-transplant lymphoproliferative disorder (PTLD)","aka":["PTLD","EBV-positive PTLD","Immunodeficiency-associated lymphoproliferative disorder"],"tldr":"After an organ or stem cell transplant, the drugs that stop rejection also stop the immune system from policing Epstein-Barr virus, and infected B cells can grow into a lymphoma. The first move is to ease the immunosuppression; then the antibody rituximab, chemotherapy if needed, and, newest of all, off-the-shelf virus-specific T cells that restore the missing immune control.","summary":"PTLD spans a spectrum from EBV-driven polyclonal hyperplasia to monomorphic lymphoma (usually diffuse large B-cell, sometimes Burkitt, plasmablastic, T-cell or Hodgkin-like), classified under WHO 2022 as lymphoid proliferations and lymphomas associated with immune deficiency and dysregulation. EBV is detectable in most early and paediatric cases and about half of late adult cases; EBV-negative PTLD arises later and behaves like de novo lymphoma. Risk is driven by the degree of T-cell suppression (T-cell-depleting induction, tacrolimus-based regimens), EBV-seronegative recipients of seropositive organs (the paediatric scenario), and organ type. In allogeneic stem cell transplant the risk factors are T-cell depletion, mismatched or cord blood donors and anti-thymocyte globulin.\n\nManagement is stepwise. Reduction of immunosuppression is the first intervention and alone induces remission in a minority, at the cost of rejection risk. Rituximab monotherapy follows for CD20-positive disease; the PTLD-1 trial (Trappe and colleagues, Lancet Oncology 2012) established sequential therapy with four doses of rituximab followed by CHOP, and its risk-stratified successor (JCO 2017) showed that patients in complete remission after rituximab can continue rituximab alone, reserving CHOP for the rest. Surgery or radiotherapy handles localised disease, and EBV DNA monitoring with pre-emptive rituximab is standard after high-risk stem cell transplants. The newest treatment restores what was lost: EBV-specific cytotoxic T cells. Tabelecleucel (Ebvallo), an allogeneic, HLA-matched, off-the-shelf EBV-specific T-cell product, received European approval in December 2022 for relapsed or refractory EBV-positive PTLD after at least one prior therapy, on the basis of the ALLELE study; in the United States it received a complete response letter in January 2025 tied to manufacturing inspection findings and it does not yet appear on the FDA list of approved cellular and gene therapy products, so US patients access EBV-specific T cells through trials and academic programmes. CD19 CAR-T and bispecific antibodies have been used in small numbers of refractory patients.\n\nOpen problems are the outcome of rituximab-refractory disease, balancing rejection against lymphoma control, EBV vaccination for seronegative transplant candidates, and paediatric access to virus-specific T cells.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Post-transplant_lymphoproliferative_disorder","links":[{"label":"NCI PDQ: adult non-Hodgkin lymphoma (post-transplant lymphoproliferative disorder)","url":"https://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq"},{"label":"PTLD-1 sequential treatment (Lancet Oncol 2012)","url":"https://doi.org/10.1016/S1470-2045(11)70300-X"},{"label":"PTLD-1 risk-stratified sequential treatment (JCO 2017)","url":"https://doi.org/10.1200/JCO.2016.69.3564"},{"label":"EMA: Ebvallo (tabelecleucel)","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/ebvallo"},{"label":"BSH guideline on PTLD (Br J Haematol 2021)","url":"https://doi.org/10.1111/bjh.17421"}],"tags":["nci-coverage","rare","haematologic","virus-associated"],"related":["dlbcl","hiv-associated-lymphoma","burkitt-lymphoma","hodgkin-lymphoma","primary-cns-lymphoma"],"cancers":[],"sections":[],"technologies":["monoclonal-antibody","allogeneic-cell-therapy","allogeneic-hsct","cytotoxic-chemotherapy","car-t","bispecific-antibody"],"targets":["cd20","cd19"],"drugs":["rituximab","cyclophosphamide","doxorubicin","vincristine","axicabtagene-ciloleucel","glofitamab","epcoritamab"],"companies":[],"institutions":[],"pathways":["oncogenic-viruses","antigen-presentation-immunoediting"],"terms":["ebv-term","plasma-ebv-dna","allogeneic-transplant","gvhd"],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-manufacturing-cell-therapy"],"keyPapers":["paper-trappe-lancet-oncol","paper-shah-br-j-haematol"],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"Occurs after roughly one to twenty percent of solid organ transplants depending on organ, EBV serostatus and age (highest in EBV-seronegative children receiving intestinal or lung grafts), and after a small percentage of allogeneic stem cell transplants (ISHLT; CIBMTR).","subtypes":["Non-destructive PTLD (plasmacytic hyperplasia, infectious mononucleosis-like, florid follicular hyperplasia)","Polymorphic PTLD","Monomorphic PTLD, B-cell (DLBCL-like, Burkitt-like, plasmablastic)","Monomorphic PTLD, T/NK-cell","Classical Hodgkin lymphoma-like PTLD","EBV-negative (late) PTLD"],"biomarkers":["EBV status of tumour (EBER in situ hybridisation) and plasma EBV DNA load","CD20 expression (rituximab eligibility)","Recipient EBV serostatus at transplant","Type and intensity of immunosuppression","LDH, stage, performance status and graft involvement (prognostic index)","HLA type (for matched EBV-specific T-cell products)"],"standardOfCare":[{"setting":"All PTLD, first step","approach":"Reduce immunosuppression as far as graft safety allows, with close monitoring for rejection; surgery or radiotherapy for localised disease.","refs":["ebv-term"],"guideline":{"version":"BSH guideline on PTLD (Br J Haematol 2021); ECIL guidelines for EBV after HSCT","url":"https://doi.org/10.1111/bjh.17421"}},{"setting":"CD20-positive PTLD not responding to reduced immunosuppression","approach":"Rituximab weekly for four doses; patients in complete remission continue rituximab consolidation alone, others proceed to R-CHOP (PTLD-1 risk-stratified sequential treatment).","refs":["rituximab","cyclophosphamide","doxorubicin","vincristine","cd20","ptld-1"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: B-Cell Lymphomas (PTLD); PTLD-1 RSST (JCO 2017)","url":"https://doi.org/10.1200/JCO.2016.69.3564"}},{"setting":"EBV-positive, relapsed or refractory","approach":"EBV-specific T cells: tabelecleucel (EMA approval 2022; under FDA review) or institutional virus-specific T-cell programmes; clinical trials.","refs":["allogeneic-cell-therapy","ebv-term"],"guideline":{"version":"EMA: Ebvallo (tabelecleucel) EPAR"}},{"setting":"After allogeneic HSCT, high risk","approach":"Weekly plasma EBV DNA monitoring with pre-emptive rituximab when load rises; reduction of immunosuppression where possible.","refs":["rituximab","allogeneic-hsct","plasma-ebv-dna"],"guideline":{"version":"ECIL-6 guidelines (Haematologica 2016)","url":"https://doi.org/10.3324/haematol.2016.144428"}}],"stateOfArt":["Risk-stratified sequential therapy (rituximab, then rituximab alone or R-CHOP by response) gives high response rates with less chemotherapy than lymphoma-standard regimens.","Off-the-shelf EBV-specific T cells restore immune control of the virus; tabelecleucel is approved in Europe and is the first allogeneic T-cell therapy approved anywhere.","Pre-emptive rituximab guided by EBV DNA load has made PTLD after stem cell transplant largely preventable.","Better induction and maintenance immunosuppression choices, and EBV-mismatch awareness in paediatric transplantation, reduce incidence."],"history":[{"year":1968,"title":"First reports of lymphoma after kidney transplantation","note":"Doak and colleagues; Penn's registry (1969) establishes the association with immunosuppression.","refs":[]},{"year":1980,"title":"EBV linked to PTLD","note":"Hanto and colleagues show EBV in lymphoproliferations of transplant recipients and regression with reduced immunosuppression.","refs":[]},{"year":1994,"title":"Donor-derived EBV-specific T cells prevent and treat PTLD","note":"Rooney, Heslop and colleagues (Lancet 1995) after stem cell transplant.","refs":["allogeneic-cell-therapy"]},{"year":2000,"title":"Rituximab in PTLD","note":"Case series and the French multicentre trial (Blood 2006) establish anti-CD20 therapy.","refs":["rituximab"]},{"year":2012,"title":"PTLD-1: sequential rituximab then CHOP","note":"Trappe and colleagues, Lancet Oncology 2012.","refs":["rituximab"]},{"year":2017,"title":"Risk-stratified sequential treatment","note":"Rituximab consolidation alone for complete responders (JCO 2017).","refs":["rituximab"]},{"year":2022,"title":"Tabelecleucel approved in the EU","note":"First allogeneic T-cell immunotherapy approved; December 2022, for relapsed or refractory EBV-positive PTLD.","refs":["allogeneic-cell-therapy"]}],"pipeline":["allogeneic-cell-therapy","rituximab","glofitamab","epcoritamab"],"openProblems":["Rituximab-refractory and EBV-negative PTLD have poor outcomes; EBV-specific T cells, CAR-T and bispecific antibodies are the routes being tested.","US access to tabelecleucel awaits FDA resolution of manufacturing findings; academic virus-specific T-cell banks fill the gap.","Balancing graft rejection against lymphoma control when immunosuppression is reduced; mTOR-inhibitor conversion and tailored regimens are studied.","Preventing PTLD in EBV-seronegative children needing transplants; EBV vaccine candidates are in early trials."],"parent":"non-hodgkin-lymphoma"},"route":"/cancers/post-transplant-lymphoproliferative-disorder/","neighbours":{"cancer":[{"id":"burkitt-lymphoma","kind":"cancer","name":"Burkitt lymphoma","route":"/cancers/burkitt-lymphoma/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"ebv-positive-dlbcl","kind":"cancer","name":"EBV-positive diffuse large B-cell lymphoma","route":"/cancers/ebv-positive-dlbcl/"},{"id":"hepatosplenic-t-cell-lymphoma","kind":"cancer","name":"Hepatosplenic T-cell lymphoma","route":"/cancers/hepatosplenic-t-cell-lymphoma/"},{"id":"hiv-associated-lymphoma","kind":"cancer","name":"HIV-associated (AIDS-related) lymphomas","route":"/cancers/hiv-associated-lymphoma/"},{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"},{"id":"lymphomatoid-granulomatosis","kind":"cancer","name":"Lymphomatoid granulomatosis","route":"/cancers/lymphomatoid-granulomatosis/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"primary-cns-lymphoma","kind":"cancer","name":"Primary CNS lymphoma","route":"/cancers/primary-cns-lymphoma/"}],"technology":[{"id":"allogeneic-cell-therapy","kind":"technology","name":"Allogeneic (off-the-shelf) cell therapy","route":"/technologies/allogeneic-cell-therapy/"},{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"},{"id":"bispecific-antibody","kind":"technology","name":"Bispecific antibodies","route":"/technologies/bispecific-antibody/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}],"target":[{"id":"cd19","kind":"target","name":"CD19","route":"/targets/cd19/"},{"id":"cd20","kind":"target","name":"CD20","route":"/targets/cd20/"}],"drug":[{"id":"axicabtagene-ciloleucel","kind":"drug","name":"Axicabtagene ciloleucel","route":"/drugs/axicabtagene-ciloleucel/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"epcoritamab","kind":"drug","name":"Epcoritamab","route":"/drugs/epcoritamab/"},{"id":"glofitamab","kind":"drug","name":"Glofitamab","route":"/drugs/glofitamab/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"tabelecleucel","kind":"drug","name":"Tabelecleucel","route":"/drugs/tabelecleucel/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"pathway":[{"id":"antigen-presentation-immunoediting","kind":"pathway","name":"Antigen presentation & immune editing","route":"/pathways/antigen-presentation-immunoediting/"},{"id":"oncogenic-viruses","kind":"pathway","name":"Oncogenic viruses","route":"/pathways/oncogenic-viruses/"}],"term":[{"id":"allogeneic-transplant","kind":"term","name":"Allogeneic stem cell transplant (allo-SCT)","route":"/terms/allogeneic-transplant/"},{"id":"ebv-term","kind":"term","name":"Epstein-Barr virus (EBV) in cancer","route":"/terms/ebv-term/"},{"id":"gvhd","kind":"term","name":"Graft-versus-host disease (GVHD) and graft-versus-leukaemia","route":"/terms/gvhd/"},{"id":"plasma-ebv-dna","kind":"term","name":"Plasma EBV DNA","route":"/terms/plasma-ebv-dna/"}],"bottleneck":[{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","route":"/bottlenecks/b-manufacturing-cell-therapy/"},{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"}],"paper":[{"id":"paper-shah-br-j-haematol","kind":"paper","name":"Front-line management of post-transplantation lymphoproliferative disorder in adult solid organ recipient patients - A British Society for Haematology Guideline","route":"/key-papers/paper-shah-br-j-haematol/"},{"id":"paper-ptld-1-risk-stratified-sequential-treatment-trappe-jco-2017","kind":"paper","name":"PTLD-1: response to rituximab induction as a predictive marker allowing stratification into rituximab or R-CHOP consolidation in B-cell post-transplant lymphoproliferative disorder","route":"/key-papers/paper-ptld-1-risk-stratified-sequential-treatment-trappe-jco-2017/"},{"id":"paper-trappe-lancet-oncol","kind":"paper","name":"Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial","route":"/key-papers/paper-trappe-lancet-oncol/"},{"id":"paper-epstein-virus-particles-burkitt-lymphoblasts-lancet-1964","kind":"paper","name":"Virus particles in cultured lymphoblasts from Burkitt's lymphoma","route":"/key-papers/paper-epstein-virus-particles-burkitt-lymphoblasts-lancet-1964/"}],"trial":[{"id":"nct03394365","kind":"trial","name":"A Phase 3 Study of Tabelecleucel for Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failu","route":"/trials/nct03394365/"},{"id":"ptld-1","kind":"trial","name":"PTLD-1","route":"/trials/ptld-1/"}]}}