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Blood Oct 2023Posttransplant lymphoproliferative disorder (PTLD) is an important and potentially life-threatening complication of solid organ transplant and hematopoietic stem cell...
Posttransplant lymphoproliferative disorder (PTLD) is an important and potentially life-threatening complication of solid organ transplant and hematopoietic stem cell transplant (HSCT). Given the heterogeneity of PTLD and the risk of infectious complications in patients with immunosuppression, the treatment of this disease remains challenging. Monomorphic PTLD and lymphoma of B-cell origin account for the majority of cases. Treatment strategies for PTLD consist of response-adapted, risk-stratified methods using immunosuppression reduction, immunotherapy, and/or chemotherapy. With this approach, ∼25% of the patients do not need chemotherapy. Outcomes for patients with high risk or those who do not respond to frontline therapies remain dismal, and novel treatments are needed in this setting. PTLD is associated with Epstein-Barr virus (EBV) infection in 60% to 80% of cases, making EBV-directed therapy an attractive treatment modality. Recently, the introduction of adoptive immunotherapies has become a promising option for refractory cases; hopefully, these treatment strategies can be used as earlier lines of therapy in the future.
Topics: Humans; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Organ Transplantation; Transplantation, Homologous; Lymphoproliferative Disorders
PubMed: 37540819
DOI: 10.1182/blood.2023020075 -
British Journal of Haematology May 2023Post-transplant lymphoproliferative disorder (PTLD) is rare and heterogeneous lymphoid proliferations that occur as a result of immunosuppression following solid organ... (Review)
Review
Post-transplant lymphoproliferative disorder (PTLD) is rare and heterogeneous lymphoid proliferations that occur as a result of immunosuppression following solid organ transplant (SOT) and haematopoietic stem cell transplant (HSCT) with the majority being driven by EBV. Although some histologies are similar to lymphoid neoplasms seen in immunocompetent patients, treatment of PTLD may be different due to difference in pathobiology and higher risk of treatment complications. The most common treatment approach in SOT PTLD after failing immunosuppression reduction (RIS) takes into consideration a risk-stratified sequential algorithm with rituximab +/- chemotherapy based on phase 2 studies. In HSCT PTLD, RIS alone and chemotherapy are usually ineffective making rituximab +/- RIS as the gold standard of frontline treatment. In this review, we give an update on the treatment of PTLD beyond RIS. We highlight the most recent studies that attempted to incorporate more aggressive chemotherapy regimens and novel treatments into the traditional risk-stratified sequential approach. We also discuss the role of EBV-cytotoxic T lymphocytes in treatment of EBV-driven PTLD. Other novel agents with potential role in PTLD will be discussed in addition to the challenges that could arise with chimeric antigen receptor T-cell therapy and immune checkpoint inhibitors in this population.
Topics: Humans; Rituximab; Epstein-Barr Virus Infections; Lymphoproliferative Disorders; Organ Transplantation; Lymphoma
PubMed: 36946218
DOI: 10.1111/bjh.18763 -
Radiographics : a Review Publication of... 2020(Review)
Review
Topics: Child; Diagnosis, Differential; Humans; Immunocompromised Host; Lymphoproliferative Disorders; Organ Transplantation; Postoperative Complications; Risk Factors
PubMed: 31834850
DOI: 10.1148/rg.2020190103 -
Respiration; International Review of... 2017This review aims to describe some of the most frequent lymphoproliferative disorders arising from the lung: pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma,... (Review)
Review
This review aims to describe some of the most frequent lymphoproliferative disorders arising from the lung: pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma, lymphomatoid granulomatosis (LG), multicentric Castleman disease (MCD), primary effusion lymphoma (PEL), and nodular lymphoid hyperplasia (NLH). Primary pulmonary lymphoma is defined as a clonal lymphoproliferative disorder affecting one or both lungs, without extrapulmonary involvement 3 months after diagnosis, and includes pulmonary MALT lymphoma and LG. MALT lymphoma is the most common pulmonary lymphoma. The disease is slow growing, most often asymptomatic, and revealed by chronic alveolar opacity on radiography. The diagnosis should involve minimally invasive techniques, and the prognosis is typically excellent. LG is a rare B-cell lymphoma driven by Epstein-Barr virus infection. The disease may mimic pulmonary vasculitis, often revealed by systemic signs. The diagnosis usually requires surgical lung biopsy. Its evolution is unpredictable, but median survival is poor and chemotherapy is usually proposed. MCD and PEL are both driven by Human herpesvirus 8 infection. Patients with MCD present with fever and lymphadenopathy associated with interstitial lung disease. PEL provokes a febrile, lymphocytic-exudative pleural effusion, without any pleural mass on CT. Specific chemotherapy is urgent for both MCD and PEL. NLH is a benign lymphoproliferative disorder of the lung that is usually asymptomatic and revealed by a single nodular opacity. The prognosis is good, without recurrence after surgical resection.
Topics: Castleman Disease; Epstein-Barr Virus Infections; Herpesviridae Infections; Herpesvirus 8, Human; Humans; Lung Diseases; Lung Neoplasms; Lymphoma; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Primary Effusion; Lymphomatoid Granulomatosis; Lymphoproliferative Disorders
PubMed: 28609772
DOI: 10.1159/000477740 -
Otolaryngology--head and Neck Surgery :... Nov 2017Objective Posttransplant lymphoproliferative disorder (PTLD) is a unifying term for a spectrum of lymphoid expansion entities brought about by immunosuppression and is... (Review)
Review
Objective Posttransplant lymphoproliferative disorder (PTLD) is a unifying term for a spectrum of lymphoid expansion entities brought about by immunosuppression and is strongly associated with Epstein-Barr virus (EBV). Otolaryngological findings tend to present early in the clinical course; therefore, disease awareness among otolaryngologists is of utmost importance. This review synthesizes the body of literature pertaining to PTLD involving the head and neck, summarizes contemporary management, and highlights areas for future research. Data Sources PubMed/Medline. Review Methods Primary literature search of the Medline database was performed for all titles published in the past 10 years pertaining to PTLD. The database search included PTLD combined with a collection of otolaryngological MeSH terms. Full manuscripts were reviewed based on relevance of their title and abstract. Selection into this review was according to clinical and scientific relevance. Conclusion Adenotonsillar focus is common in children in whom adenotonsillectomy may be diagnostic and prevents potentially morbid airway obstruction. Sinonasal PTLD may mimic fungal infection. Laryngotracheal involvement predominately presents in children with symptoms of airway obstruction. PTLD limited to the esophagus is rare. Oral PTLD is rare and phenotypically varied. Cutaneous presentation of PTLD is infrequent, yet one-third of cases affects the head and neck. PTLD may present as cervical lymphadenopathy. Implications for Practice PTLD consideration is vital when evaluating posttransplant patients. Children and EBV-seronegative patients should receive otolaryngological follow-up after transplant. PTLD treatment is multidisciplinary and typically led by lymphoma specialists. Formal partnerships between otolaryngologists and transplant centers may improve patient care and research quality.
Topics: Epstein-Barr Virus Infections; Humans; Immunosuppression Therapy; Lymphoproliferative Disorders; Organ Transplantation; Otorhinolaryngologic Diseases; Postoperative Complications
PubMed: 28535360
DOI: 10.1177/0194599817707208 -
Nihon Rinsho Men'eki Gakkai Kaishi =... 2017Methotrexate-associated lymphproliferative disorder (MTX-LPD) is a rare but critical complication developing in patients treated with methotrexate. Now that methotrexate... (Review)
Review
Methotrexate-associated lymphproliferative disorder (MTX-LPD) is a rare but critical complication developing in patients treated with methotrexate. Now that methotrexate is an anchor drug in the management of rheumatoid arthritis and become commonly used, MTX-LPD cases have increased. Many things has been unclear such as incidence, demographic characters, and risk factors. However, as the researches increased, several interesting topics has been demonstrated like associations with Epsteiin-Barr virus and with cell-mediated immunity. This report reviews newly the latest findings and future challenges on MTX-LPD.
Topics: Age Factors; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Herpesvirus 4, Human; Humans; Immunity, Cellular; Lymphoproliferative Disorders; Male; Methotrexate; Prognosis; Risk Factors
PubMed: 28747604
DOI: 10.2177/jsci.40.174 -
Annals of Hematology Oct 2020Germinotropic lymphoproliferative disorder is a rare and rather enigmatic novel entity with distinctive clinicopathological features, one of which is the typical...
Germinotropic lymphoproliferative disorder is a rare and rather enigmatic novel entity with distinctive clinicopathological features, one of which is the typical co-infection by Human herpesvirus 8 and Epstein-Barr virus. Human herpesvirus 8 is a lymphotropic virus detected in Kaposi sarcoma, multicentric Castleman disease, primary effusion lymphoma, Human herpesvirus 8-positive diffuse large B cell lymphoma not otherwise specified, and germinotropic lymphoproliferative disorder. Co-infection by Human herpesvirus 8 and Epstein-Barr virus is identified only in two lymphoproliferative diseases: germinotropic lymphoproliferative disorder and primary effusion lymphoma, which are otherwise diseases with totally different clinical presentations and outcomes. Unlike primary effusion lymphoma mostly occurring in immunocompromised individuals and following an aggressive course, germinotropic lymphoproliferative disorder usually presents with single or multiple lymphadenopathy affecting mainly immunocompetent individuals and mostly follows an indolent course. Based on the PRISMA guidelines, we carried out a systematic search on PubMed/MEDLINE, Web of Science, Scopus, EMBASE, and Cochrane Library using the search terms "germinotropic" and "lymphoproliferative disorder." Current scientific literature reports just 19 cases of germinotropic lymphoproliferative disorder. The purpose of our systematic review is to improve our understanding of the disease, focusing on epidemiology, clinical presentation, pathological features, treatment, and outcome. In addition, we discuss the differential diagnosis with the other Human herpesvirus 8-related lymphoproliferative diseases as currently recognized in the World Health Organization classification, adding a focus on lymphoproliferative disorders showing overlapping features.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Coinfection; Combined Modality Therapy; Diagnosis, Differential; Disease Progression; Female; Germinal Center; Herpesviridae Infections; Herpesvirus 4, Human; Herpesvirus 8, Human; Humans; Immunocompetence; Lymph Nodes; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Primary Effusion; Lymphoproliferative Disorders; Male; Middle Aged; Treatment Outcome
PubMed: 32307569
DOI: 10.1007/s00277-020-04024-3 -
The Annals of Pharmacotherapy Nov 2007To define and discuss the pathogenesis, clinical presentation, diagnosis, risk factors, and current preventive and treatment strategies of posttransplant... (Review)
Review
OBJECTIVE
To define and discuss the pathogenesis, clinical presentation, diagnosis, risk factors, and current preventive and treatment strategies of posttransplant lymphoproliferative disorder (PTLD).
DATA SOURCES
MEDLINE was searched for articles published from January 1966 to July 2007. Search terms used include posttransplant lymphoproliferative disease, posttransplant malignancy, antiviral agents, interferon-alfa, rituximab, immunosuppression, chemotherapy, radiation, and surgery. Additional articles were identified by a hand search of references.
STUDY SELECTION AND DATA EXTRACTION
Studies in English of pediatric and adult solid organ transplantation populations published were selected and analyzed. Data from these studies and information from review articles were included in this review.
DATA SYNTHESIS
PTLD occurs in 1-20% of organ recipients following solid organ transplantation. PTLD risk factors include recipient pretransplant Epstein-Barr virus (EBV) negative serostatus, type of transplant, intensity of immunosuppression, and age. The PTLD presentation is variable. Some patients present asymptomatically; in others, early symptoms can be nonspecific. To prevent PTLD, minimizing immunosuppression burden and using antiviral agents active against EBV are useful strategies. PTLD treatment may require reduction of immunosuppression, radiation, surgical excision, monoclonal antibodies, interferon-alfa, and chemotherapy.
CONCLUSIONS
Screening for patients at risk and balancing the intensity of immunosuppressive regimens against the risk of rejection can substantially reduce the risk of developing PTLD. If PTLD occurs, an individualized treatment plan including decreased immunosuppression and other agents should be chosen based on the severity and extent of disease.
Topics: Age Factors; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antiviral Agents; Epstein-Barr Virus Infections; Humans; Immunologic Factors; Immunosuppressive Agents; Incidence; Lymphoproliferative Disorders; Organ Transplantation; Risk Factors; Rituximab
PubMed: 17940127
DOI: 10.1345/aph.1G706 -
Current Oncology Reports Aug 2023A relative lack of molecular and clinical studies compared to other lymphoid cancers has historically made it difficult to determine optimal management approaches in... (Review)
Review
PURPOSE OF REVIEW
A relative lack of molecular and clinical studies compared to other lymphoid cancers has historically made it difficult to determine optimal management approaches in post-transplant lymphoproliferative disorder (PTLD). We sought to better define the "state of the science" in PTLD by examining recent advances in risk assessment, genomic profiling, and trials of PTLD-directed therapy.
RECENT FINDINGS
Several major clinical trials highlight risk-stratified sequential therapy incorporating rituximab with or without chemotherapy as a rational treatment strategy in patients with CD20+ PTLD who do not respond to reduction of immunosuppression alone. Epstein Barr virus (EBV)-targeted cytotoxic lymphocytes are a promising approach in patients with relapsed/refractory EBV+ PTLD, but dedicated clinical trials should determine how autologous chimeric antigen receptor T cell therapy (CAR-T) may be safely administered to PTLD patients. Sequencing studies underscore the important effect of EBV infection on PTLD pathogenesis, but comprehensive genomic and tumor microenvironment profiling are needed to identify biomarkers that predict response to treatment in this clinically heterogeneous disease.
Topics: Humans; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Hematopoietic Stem Cell Transplantation; Rituximab; Lymphoproliferative Disorders
PubMed: 37162742
DOI: 10.1007/s11912-023-01418-0 -
Clinics in Chest Medicine Dec 2017Posttransplant lymphoproliferative disorders (PTLD) represent an immunosuppression-related lymphoid or plasmacytic proliferation that occur in the setting of solid organ... (Review)
Review
Posttransplant lymphoproliferative disorders (PTLD) represent an immunosuppression-related lymphoid or plasmacytic proliferation that occur in the setting of solid organ transplant or allogeneic hematopoietic stem cell transplantation (HSCT). PTLD is a devastating consequence of HSCT and solid organ transplantation with a high morbidity and mortality. Most commonly, PTLD is related to Epstein-Barr virus (EBV) infection, but an increasing number of non-EBV-related cases are occurring. Initial therapy involves withdrawal of immunosuppression with or without antibody or cytotoxic chemotherapy. Novel therapeutic approaches including EBV-specific cytotoxic T lymphocytes are currently being studied.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Lymphoproliferative Disorders; Transplantation Conditioning
PubMed: 29128025
DOI: 10.1016/j.ccm.2017.08.001