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Post-transplant lymphoproliferative disease

Kwai Fung Hui, Stephanie Pei Tung Yiu, Kam Pui Tam, Alan Kwok Shing Chiang
Epstein-Barr virus (EBV) is strongly associated with a spectrum of EBV-associated lymphoproliferative diseases (EBV-LPDs) ranging from post-transplant lymphoproliferative disorder, B cell lymphomas (e.g., endemic Burkitt lymphoma, Hodgkin lymphoma, and diffuse large B cell lymphoma) to NK or T cell lymphoma (e.g., nasal NK/T-cell lymphoma). The virus expresses a number of latent viral proteins which are able to manipulate cell cycle and cell death processes to promote survival of the tumor cells. Several FDA-approved drugs or novel compounds have been shown to induce killing of some of the EBV-LPDs by inhibiting the function of latent viral proteins or activating the viral lytic cycle from latency...
2019: Frontiers in Oncology
Shawn C West, Josh M Friedland-Little, Kenneth O Schowengerdt, David C Naftel, Elizabeth Pruitt, Kelli S Smith, Simon Urschel, Marian G Michaels, James K Kirklin, Brian Feingold
Post-transplant lymphoproliferative disorder (PTLD) is a significant complication after pediatric heart transplantation (HT), occurring in 5-15% of patients within 3 years. Data > 3 years from HT are limited. We sought to describe the prevalence, risk factors, and outcomes of PTLD occurring late (> 3 years) after pediatric HT in the Pediatric Heart Transplant Study from 1993 to 2010. Among 3,844 primary HT patients, 110 (3%) developed late, non-recurrent PTLD. The hazard rate for late PTLD was constant at 0...
March 12, 2019: Clinical Transplantation
Alexandre Fabre, Sarah Marchal, Vincent Barlogis, Bernard Mari, Pascal Barbry, Pierre-Simon Rohrlich, Lisa R Forbes, Tiphanie P Vogel, Lisa Giovannini-Chami
BACKGROUND: STAT3 gain-of-function (GOF) germline mutations have been recently described. A comprehensive overview of this early-onset multiorgan autoimmune and lymphoproliferative disease has not yet been compiled. OBJECTIVE: We have conducted a systematic review of published STAT3 GOF cases in order to describe clinical, diagnostic and therapeutic aspects of the disease. METHODS: A systematic review including articles published before 10/10/2018 in Pubmed, WoS and CENTRAL databases was performed...
February 27, 2019: Journal of Allergy and Clinical Immunology in Practice
Ayumi Fujimoto, Nobuhiro Hiramoto, Satoshi Yamasaki, Yoshihiro Inamoto, Naoyuki Uchida, Tetsuo Maeda, Takehiko Mori, Yoshinobu Kanda, Tadakazu Kondo, Souichi Shiratori, Shigesaburo Miyakoshi, Ken Ishiyama, Kazuhiro Ikegame, Yoshiko Matsuhashi, Junji Tanaka, Tatsuo Ichinohe, Yoshiko Atsuta, Masao Ogata, Ritsuro Suzuki
We analyzed data of 64,539 consecutive patients in the national Japanese transplant registry, including 40,195 after allogeneic stem cell transplantation, 24,215 after autologous stem cell transplantation, and 129 after syngeneic stem cell transplantation, and 299 developed Epstein-Barr virus positive post-transplant lymphoproliferative disorder. The probability at 2 years was 0.79% after allogeneic transplantation, 0.78% after syngeneic transplantation, and 0.11% after autologous transplantation. The following variables were identified as risk factors after allogeneic transplantation in multivariate analysis: antithymocyte globulin use in a conditioning regimen, antithymocyte globulin use for acute graft-versus-host disease treatment, donors other than HLA-matched related donors, aplastic anemia, second or subsequent allogeneic transplantation, the recent year of transplantation, and acute graft-versus-host disease...
February 19, 2019: Biology of Blood and Marrow Transplantation
Ping Zhang, Jyothy Raju, Md Ashik Ullah, Raymond Au, Antiopi Varelias, Kate H Gartlan, Stuart D Olver, Luke D Samson, Elise Sturgeon, Nienke Zomerdijk, Judy Avery, Tessa Gargett, Michael P Brown, Lachlan J Coin, Devika Ganesamoorthy, Cheryl Hutchins, Gary R Pratt, Glen A Kennedy, A James Morton, Cameron I Curley, Geoffrey R Hill, Siok-Keen Tey
Purpose: Inducible caspase 9 ( iCasp9 ) is a cellular safety switch that can make T-cell therapy safer. The purpose of this phase I trial was to investigate the use of iCasp9 -transduced T-cell addback in adult patients undergoing haploidentical stem cell transplantation for high-risk hematologic malignancies. Patients and Methods: Patients undergoing myeloablative, CD34-selected haploidentical stem cell transplantation were treated with 0.5-1.0 × 106 /kg donor-derived iCasp9 -transduced T cells on day +25 or 26 post-transplant, with additional doses allowed for disease relapse, infection, or mixed chimerism...
February 14, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
R Borrows, A Scheer, P Cockwell, F Braun, I Anagnostopoulos, H Riess, H Zimmermann, R U Trappe
Post-transplant lymphoproliferative disease (PTLD) is a serious complication of solid organ transplantation. As early diagnosis remains challenging, we investigated the utility of serum-free light chain (FLC) and heavy chain/light chain pairs (HLC) as diagnostic biomarkers. Pre-treatment serum FLC and HLC levels were measured in 20 patients at their first diagnosis of B cell PTLD and in 14/20 patients during follow-up. Results were compared to serum FLC/HLC levels of 90 matched PTLD-free transplanted controls...
January 25, 2019: Annals of Hematology
Mari Kannagi, Atsuhiko Hasegawa, Yoshiko Nagano, Tadafumi Iino, Jun Okamura, Youko Suehiro
Adult T-cell leukemia/lymphoma (ATL) is an aggressive lymphoproliferative disease caused by human T-cell leukemia virus type 1 (HTLV-1). Multi-agent chemotherapy can reduce ATL cells but frequently allows relapses within a short period of time. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) following chemotherapy is now a standard therapy for ATL in Japan as it can achieve long-term remission in approximately one-third of recipient ATL patients; however, it also has a risk of treatment-related mortality...
January 22, 2019: Cancer Science
Yusuke Okuno, Takayuki Murata, Yoshitaka Sato, Hideki Muramatsu, Yoshinori Ito, Takahiro Watanabe, Tatsuya Okuno, Norihiro Murakami, Kenichi Yoshida, Akihisa Sawada, Masami Inoue, Keisei Kawa, Masao Seto, Koichi Ohshima, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Yohei Narita, Masahiro Yoshida, Fumi Goshima, Jun-Ichi Kawada, Tetsuya Nishida, Hitoshi Kiyoi, Seiichi Kato, Shigeo Nakamura, Satoko Morishima, Tetsushi Yoshikawa, Shigeyoshi Fujiwara, Norio Shimizu, Yasushi Isobe, Masaaki Noguchi, Atsushi Kikuta, Keiji Iwatsuki, Yoshiyuki Takahashi, Seiji Kojima, Seishi Ogawa, Hiroshi Kimura
Epstein-Barr virus (EBV) infection is highly prevalent in humans and is implicated in various diseases, including cancer1,2 . Chronic active EBV infection (CAEBV) is an intractable disease classified as a lymphoproliferative disorder in the 2016 World Health Organization lymphoma classification1,2 . CAEBV is characterized by EBV-infected T/natural killer (NK) cells and recurrent/persistent infectious mononucleosis-like symptoms3 . Here, we show that CAEBV originates from an EBV-infected lymphoid progenitor that acquires DDX3X and other mutations, causing clonal evolution comprising multiple cell lineages...
January 21, 2019: Nature Microbiology
Lila Simakachorn, Pornthep Tanpowpong, Chatmanee Lertudomphonwanit, Usanarat Anurathapan, Samart Pakakasama, Suradej Hongeng, Suporn Treepongkaruna, Pornpimon Phuapradit
PTLD is a rare but potentially life-threatening condition, which shows a higher prevalence in children than in adults. From 129 children who underwent LT, we reported 5 cases with biopsy-proven PTLD at a single teaching hospital. Four patients had shared clinical presentations including fever, lymphadenopathy, and splenomegaly. They were noted to be given a prolonged course of IS due to the management of comorbid complications such as acute cellular rejection or severe food allergy or eosinophilic gastrointestinal disease...
January 20, 2019: Pediatric Transplantation
P Mendogni, S Henchi, L C Morlacchi, D Tosi, M Nosotti, P Tarsia, A I Gregorini, L Rosso
BACKGROUND: Solid organ transplantation is associated with a higher risk of Epstein-Barr virus (EBV)-related lymphoproliferative disease due to immunosuppressive regimen. Little evidence is currently available on post-transplant lymphoproliferative disorders (PTLDs) in the lung transplant (LuTx) setting, particularly in cystic fibrosis (CF) recipients. METHODS: We retrospectively analyzed all the cases of PTLDs that occurred in our LuTx center between January 2015 and December 2017...
January 2019: Transplantation Proceedings
Chien-Ting Hsu, Mei-Hwei Chang, Ming-Chih Ho, Hsiu-Hao Chang, Meng-Yao Lu, Shiann-Tarng Jou, Yen-Hsuan Ni, Huey-Ling Chen, Hong-Yuan Hsu, Jia-Feng Wu
BACKGROUND: Post-transplantation lymphoproliferative disorder (PTLD) is a heterogeneous, potentially life-threatening complication after liver transplantation in children. In this study, the disease characteristics, outcomes, and prognostic factors of PTLD were investigated. METHODS: A retrospective, observational study was conducted on 16 pediatric liver transplant (LT) recipients who developed PTLD between February 2001 and December 2013 at a tertiary referral center in Taiwan...
January 8, 2019: Journal of the Formosan Medical Association
Udit Dhal, Shine Raju, Arun D Singh, Atul C Mehta
Ophthalmic complications in the lung transplant population are a little-known entity. It includes a spectrum of diseases ranging from infections such as cytomegalovirus (CMV) retinitis, herpetic keratitis, Pseudallescheria boydii to non-infectious complications such as posterior subcapsular cataracts (PSCs), cyclosporine retinopathy, and post-transplant lymphoproliferative disorder (PTLD). These diseases can be attributed to high levels of immunosuppression, advanced age, and drug-specific side effects. Underlying comorbidities such as diabetes mellitus may also play a role in the pathogenesis...
November 2018: Journal of Thoracic Disease
Cristina Valencia-Sanchez, Kristen K Steenerson, Katalin Kelemen, Robert Orenstein, Shimon Kusne, Marie F Grill
Post-transplantation lymphoproliferative disorder (PTLD) is a complication of solid organ and hematopoietic stem cell transplantation. Cases with isolated central nervous system (CNS) disease are rare. Epstein-Barr virus (EBV) plays a causative role. We present a patient with EBV cerebellitis documented 5 months prior to development of primary CNS PTLD (PCNS-PTLD). This case report demonstrates progression from EBV CNS infection to lymphoproliferative disorder, highlighting the importance of serial clinical and imaging monitoring in transplant patients post-EBV CNS infection...
January 3, 2019: Journal of Neurovirology
Joana Marinho-Dias, Inês Baldaque, Carlos Pinho-Vaz, Luís Leite, Rosa Branca, Fernando Campilho, António Campos, Rui Medeiros, Hugo Sousa
The identification of patients at higher risk of developing Epstein‑Barr virus (EBV) infection in hematopoietic stem cell transplants (HSCT) is useful for the prevention of EBV‑associated diseases A prospective observational study was developed that included 40 patients (27 male and 13 females, with mean age of 32.2±1.5 years old) undergoing allogeneic‑HSCT between January and December 2015. EBV was examined in whole blood samples collected during routine procedures at day (D)+30, D +60, +90, D+120, D+150 and D+180 post‑transplant...
December 24, 2018: Molecular Medicine Reports
Yuki Kimura, Masanobu Yanase, Hiroki Mochizuki, Keiichiro Iwasaki, Koichi Toda, Sachi Matsuda, Hiromi Takenaka, Yuto Kumai, Kensuke Kuroda, Seiko Nakajima, Takuya Watanabe, Megumi Morii Ikura, Kyoichi Wada, Yorihiko Matsumoto, Osamu Seguchi, Satsuki Fukushima, Tomoyuki Fujita, Junjiro Kobayashi, Norihide Fukushima
BACKGROUND: Because of aggressive immunosuppression, heart transplant recipients have a high risk of de novo malignancy, which is a major cause of death and worse prognosis, regardless of the type. However, the impact of de novo malignancy on Japanese heart transplant recipients is unknown. METHODS: We analyzed 103 Japanese heart transplant recipients over 18-years-old at the time of transplantation between April 1999 and April 2017. Patient characteristics and prognosis were compared between heart transplant recipients with or without de novo malignancy after heart transplantation (HTx)...
December 22, 2018: Journal of Cardiology
Emily M Engelhardt, Andrew T Trout, Rachel M Sheridan, Gruschen R Veldtman, Jonathan R Dillman
PURPOSE: Patients who have undergone Fontan palliation of single ventricle physiology congenital heart disease are prone to developing focal liver lesions. In our experience, the variety of lesions occurring in this population is greater than that described in the literature. The purpose of this study was to describe the breadth of biopsy-proven liver lesions in patients post-Fontan palliation of single ventricle physiology cared for at our institution. METHODS: We retrospectively identified patients who had previously undergone the Fontan operation and had a focal liver lesion biopsied between January 2000 and June 2018...
December 20, 2018: Congenital Heart Disease
Richard Heyes, Courtney M Tomblinson, David G Lott
Post-transplant lymphoproliferative disorder (PTLD) is a unifying term for a spectrum of lymphoid expansion entities brought about by immunosuppression. It can present throughout the head and neck, and tonsillar involvement is not limited to children. We report the case of a 67-year-old woman who developed odynophagia associated with putrid halitosis 4 months after she had undergone renal transplantation. Direct visualization of the oropharynx revealed multiple sites of severe ulceration and erythema, with erosion of both the anterior and posterior right tonsillar pillars and a necrotic ulceration fistulating deeply...
December 2018: Ear, Nose, & Throat Journal
Juliette Fulham, Micaela Plucinski
Post-transplant lymphoproliferative disorders (PTLD) are lymphomas that may arise in organ, bone marrow or stem cell transplant recipients who are taking immunosuppressive drugs to prevent rejection of the transplant. The likelihood of developing PTLD depends on the type of transplant. PTLD is a potentially severe complication of post-transplant treatment, with an uncertain prognosis. Lymphoproliferative disorders can also occur in people taking immunosuppressants for inflammatory bowel disease. This article will explore PTLD and discuss the experience of caring for patients who developed lymphoproliferative conditions and required emergency stoma formation...
December 13, 2018: British Journal of Nursing: BJN
Akihisa Sawada, Masami Inoue
Chronic active Epstein-Barr virus infection (CAEBV) is a prototype of EBV-associated T- and/or NK-cell (EBV+ T/NK-cell) lymphoproliferative disorders. Most subtypes of these are lethal. We established a unified treatment strategy composed of step 1 (immunochemotherapy: steroids, cyclosporine A, and etoposide), step 2 (multi-drug block chemotherapy), and step 3 (allogeneic hematopoietic stem cell transplantation; HSCT) for CAEBV and its related diseases. Allogeneic HSCT is the only cure for CAEBV with few exceptions...
2018: Frontiers in Pediatrics
Akihiro Tamura, Suguru Uemura, Nobuyuki Yamamoto, Atsuro Saito, Aiko Kozaki, Kenji Kishimoto, Toshiaki Ishida, Daiichiro Hasegawa, Haruka Hiroki, Tsubasa Okano, Kohsuke Imai, Tomohiro Morio, Hirokazu Kanegane, Yoshiyuki Kosaka
Background: X-linked lymphoproliferative disease type 1 (XLP1) is a rare primary immune deficiency, which is caused by SH2D1A gene mutations. XLP1 is commonly associated with Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis, hypogammaglobulinemia, and/or lymphoma. The only curative treatment for XLP1 is allogeneic hematopoietic cell transplantation. However, published data detailing the clinical course of, and indications for, allogeneic hematopoietic cell transplantation in asymptomatic patients with XLP1 is lacking...
2018: Allergy, Asthma, and Clinical Immunology
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