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Ayca Kiykim, Louis Marie Charbonnier, Arzu Akcay, Elif Karakoc-Aydiner, Ahmet Ozen, Gulyuz Ozturk, Talal A Chatila, Safa Baris
PURPOSE: Human signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations present with a broad range of manifestations ranging from chronic mucocutaneous candidiasis and autoimmunity to combined immunodeficiency (CID). So far, there is very limited experience with hematopoietic stem cell transplantation (HSCT) as a therapeutic modality in this disorder. Here, we describe two patients with heterozygous STAT1 GOF mutations mimicking CID who were treated with HSCT...
December 13, 2018: Journal of Clinical Immunology
Attilio Bondanza, Loredana Ruggeri, Maddalena Noviello, Dirk-Jan Eikema, Chiara Bonini, Christian Chabannon, Steffie van der Werf, Anja van Biezen, Liesbeth C de Wreede, Lara Crucitti, Luca Vago, Mara Merluzzi, Maria Speranza Massei, Hendrik Veelken, Yener Koc, Peter Bader, Bernd Gruhn, Franco Locatelli, Fabio Ciceri, Antoine Toubert, Andrea Velardi
HLA-haploidentical haematopoietic stem cell transplantation (haplo-HSCT) is increasingly offered to patients with high-risk acute leukaemia. Unfortunately, haplo-HSCT is followed by a delayed immunoreconstitution. The aim of this EBMT registry study was to explore the clinical impact of lymphocyte subset counts after haplo-HSCT. We considered 144 leukaemic patients transplanted in the period 2001-2012. Pre-transplantation clinical variables and differential immune-cell counts (CD3, CD4, CD8 T cells, NK and B cells) measured before day 100 were evaluated for their capacity to predict overall survival, relapse mortality or non-relapse mortality (NRM)...
December 7, 2018: Bone Marrow Transplantation
S R Safayi, F Shahi, M Ghalamkari, M Mirzania, M Khatuni, F Hirmandi Niasar
Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially cure for acute myeloid leukemia (AML). Patients who undergone HSCT are at increased risk of infection due to impaired immunity. Objective: To evaluate the rate of bacterial, viral and fungal infection and its relationship with 2-year overall survival of AML patients who had undergone HSCT. Methods: This was a retrospective cross-sectional study of 49 patients who underwent allogenic bone marrow transplantation (BMT) from full-matched donors at BMT Center, Imam Khomeini Hospital Complex, Tehran, Iran, from 2006 to 2013...
2018: International Journal of Organ Transplantation Medicine
Wolfgang Schwinger, Christian Urban, Raphael Ulreich, Daniela Sperl, Anna Karastaneva, Volker Strenger, Herwig Lackner, Kaan Boztug, Michael H Albert, Martin Benesch, Markus G Seidel
Early diagnosis of primary immunodeficiency disorders (PID) is vital and allows directed treatment, especially in syndromes with severe or profound combined immunodeficiency. In PID patients with perinatal CMV or other opportunistic, invasive infections (e.g., Pneumocystis or Aspergillus ), multi-organ morbidity may already arise within the first months of life, before hematopoietic stem cell transplantation (HSCT) or gene therapy can be undertaken, compromising the definitive treatment and outcome. Deficiency of Wiskott-Aldrich syndrome (WAS) protein-interacting protein (WIP deficiency) causes an autosomal recessive, WAS-like syndrome with early-onset combined immunodeficiency that has been described in three pedigrees to date...
2018: Frontiers in Immunology
Jun Yang, Jieling Jiang, Yu Cai, Su Li, Liping Wan, Jun Zhu, Huixia Liu, Shan Shao, Haitao Bai, Chun Wang, Xianmin Song
Nowadays, the most wildly used regimens for graft-versus-host disease (GvHD) prophylaxis in haplo-hematopoietic stem cell transplantation (Haplo-HSCT) are based on in vivo T-cell depletion (TCD) with anti-thymocyte globulin (ATG) or posttransplant cyclophosphamide (PTCy). To improve the efficiency of GvHD prophylaxis in haploidentical peripheral blood stem cell transplantation combined with unrelated cord blood (Haplo-PBSCT-Cord), a novel regimen, which is composed of low dose of ATG (5 mg/kg) and low-dose PTCy (50 mg/kg) for GvHD prophylaxis, was evaluated in a prospective phase II clinical trial (Clinicaltrials...
November 16, 2018: Bone Marrow Transplantation
Mizuki Watanabe, Junya Kanda, Masakatsu Hishizawa, Tadakazu Kondo, Kouhei Yamashita, Akifumi Takaori-Kondo
Viral infection is a serious complication that can greatly affect patient mortality and morbidity after allogenic hematopoietic stem cell transplantation (allo-HSCT). For the early identification of patients at high risk for viral infection, we evaluated the impact of lymphocyte area under the curve (AUC) value as a new predictive factor for early immune reconstitution after allo-HSCT against viral infection. This study included 286 patients who underwent their first allo-HSCT at Kyoto University Hospital between 2005 and 2017...
October 22, 2018: Biology of Blood and Marrow Transplantation
Ewelina Pukownik, Malgorzata Kubicka, Beata Kurylo-Rafinska, Robert Debski, Przemyslaw Galazka, Krzysztof Czyzewski, Anna Krenska, Natalia Bartoszewicz, Ewa Demidowicz, Agata Marjańska, Magdalena Dziedzic, Monika Pogorzala, Mariusz Wysocki, Jan Styczynski
BACKGROUND/AIM: Immune recovery is a key factor in the management of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study analyzed the factors contributing to immune reconstitution after allo-HSCT. PATIENTS AND METHODS: Overall, 65 children with malignant or non-malignant diseases were included in multivariate analyses. RESULTS: The following factors contributed to a faster immune recovery: peripheral blood as a stem cell source and reactivation of CMV infection for CD3+ and CD4+ lymphocyte subpopulations; reactivation of CMV infection for CD8+ subset; donor EBV-IgG+ and no EBV reactivation for CD19 lymphocytes; recipient age below 10 years and peripheral blood as a stem cell source for NK cells...
October 2018: Anticancer Research
Jiexin Zhang, Xian Chen, Guodong Rong, Ting Xu, Hong Zhao, Dan Chen, Lei Wu, Peijun Huang, Fang Wang
Background: The main purpose of this study was to investigate the relationship among cytomegalovirus (CMV) viremia, peripheral immune cells alternations, and leukemia prognosis. Patients and methods: We studied 90 leukemia patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from 2008 to 2015. Their complete clinical laboratory data were collected until 1 year after transplantation. Results: All patients were serum CMV negative before allo-HSCT...
2018: OncoTargets and Therapy
J Yang, Y Cai, J L Jiang, L P Wan, H T Bai, J Zhu, S Li, X M Song, C Wang
Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for elderly patients with advanced myeloid neoplasm. Methods: From September 2014 to September 2017, 30 consecutive hospitalized 50-plus-year-old myeloid neoplasm patients were retrospectively analyzed. At the time of transplantation, 6 patients reached complete remission and the others remained no remission after treatment. The donors were identical sibling (12), matched unrelated (6) and haploidentical family member (12), respectively...
August 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Barbara Withers, Leighton Clancy, Jane Burgess, Renee Simms, Rebecca Brown, Kenneth Micklethwaite, Emily Blyth, David Gottlieb
Hematopoietic stem cell transplantation (HSCT) donor-generated virus-specific T cells (VSTs) can provide effective treatment for viral infection post-HSCT but are not readily accessible to all patients. Off-the-shelf cryopreserved VSTs suitable for treatment of multiple patients are an attractive alternative. We generated a bank of 17 cytomegalovirus (CMV)-, 14 Epstein-Barr virus (EBV)-, and 15 adenovirus (AdV)-specific T cell products from 30 third-party donors. Donors were selected for expression of 6 core HLA antigens expressed at high frequency in the local transplant population...
August 29, 2018: Biology of Blood and Marrow Transplantation
Yuriko Nishiyama-Fujita, A I Kawana-Tachikawa, Toshiaki Ono, Yukie Tanaka, Takafumi Kato, Helen E Heslop, Tomohiro Morio, Satoshi Takahashi
BACKGROUND: Restoration of virus-specific immunity by virus specific T cells (VSTs) offers an attractive alternative to conventional drugs, and can be highly effective in immunocompromised patients, including hematopoietic stem cell transplant (HSCT) recipients. However, conventional VSTs manufacture requires preparation of specialized antigen-presenting cells (APCs), prolonged ex vivo culture in serum-containing medium and antigen re-stimulation with viruses or viral vectors to provide viral antigens for presentation on APCs...
September 2018: Cytotherapy
Sarah Kraft, Noémie Bollinger, Benjamin Bodenmann, Dominik Heim, Christoph Bucher, Claudia Lengerke, Martina Kleber, Dimitrios A Tsakiris, Jakob Passweg, Alexandar Tzankov, Michael Medinger
Transplant-associated thrombotic microangiopathy (TA-TMA) remains a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We hypothesized that TA-TMA correlates with steroid-refractory acute graft-vs.-host disease (aGvHD) and assessed 660 patients suffering from either AML n = 248, ALL n = 79, CML n = 23, CLL n = 36, lymphoma/myeloma n = 127, MDS/MPN n = 124 or bone marrow failure n = 22, who met the study inclusion criteria and had undergone myeloablative (78%) and non-myeloablative (22%) allo-HSCT between 2006 and 2016...
August 14, 2018: Bone Marrow Transplantation
Chien-Ting Lin, Po-Ren Hsueh, Shang-Ju Wu, Ming Yao, Bor-Sheng Ko, Chi-Cheng Li, Cheng-An Hsu, Jih-Luh Tang, Hwei-Fang Tien
Platelet-derived growth factor receptor-alpha (PDGFRa) is a critical receptor for cytomegalovirus (CMV) entry into cells, leading to subsequent infection. This trial tested whether PDGFRa inhibition by nilotinib could prevent CMV infection in patients after allogeneic stem cell transplantation (allo-HSCT). Nilotinib (200 mg/day) was given continuously after engraftment, and plasma CMV DNA levels were monitored weekly. The primary endpoint was successful prophylaxis of CMV infection, defined as plasma CMV DNA copies less than 10,000 copies/mL, no anti-CMV treatment initiated, and no clinical CMV disease by day 100...
July 17, 2018: Biology of Blood and Marrow Transplantation
J C Cho, A D Le, S C Locke
Letermovir is a new antiviral agent with activity against human cytomegalovirus (CMV). Letermovir works as an inhibitor of the CMV DNA terminase complex which further inhibits viral DNA processing and packaging. Letermovir is available both orally and intravenously in 480-mg and 240-mg dosage forms, and is approved for use in the prophylaxis of CMV infection and disease in CMV-seropositive recipients of allogeneic hematopoietic stem cell transplant (HSCT) over the age of 18. The recommended dose is 480 mg p...
June 2018: Drugs of Today
Eric Wirtschafter, Christine VanBeek, Yuliya Linhares
Background: Bone marrow transplant-associated thrombotic microangiopathy (TA-TMA) is a relatively frequent but under-recognized and under-treated hematopoietic stem cell transplant (HSCT) complication that leads to significant post-transplant morbidity and mortality. Classic TMA-defining laboratory abnormalities appear at different times in the course of TA-TMA development, with schistocytes often appearing later in the disease course. In some severe TMA cases, schistocytes may be absent due to increased endothelial permeability...
2018: Experimental Hematology & Oncology
Brandon J Webb, Rachel Harrington, Jason Schwartz, Jennifer Kammerer, James Spalding, Edward Lee, Bart Dodds, Stephanie Kaufusi, Bruce E Goodman, Sean D Firth, Greta Martin, Jeffrey Sorensen, Daanish Hoda
BACKGROUND: CMV infection (CMV-I) remains an important complication of hematopoietic stem cell transplantation (HSCT). METHODS: This was a retrospective, single-center cohort study in HSCT recipients. Primary outcomes were adjusted cost and all-cause mortality. Secondary analyses investigated CMV risk factors and the effect of serostatus. RESULTS: Overall, 690 transplant episodes were included (allogeneic [n = 310]; autologous [n = 380])...
July 5, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Erden Atilla, Merih Yalciner, Pinar Ataca Atilla, Can Ates, Sinem Civriz Bozdag, Meltem Kurt Yuksel, Selami Kocak Toprak, Mehmet Gunduz, Mehmet Ozen, Hamdi Akan, Taner Demirer, Onder Arslan, Osman Ilhan, Meral Beksac, Muhit Ozcan, Gunhan Gurman, Pervin Topcuoglu
BACKGROUND: Hemorrhagic cystitis (HC) is usually a serious complication in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. In this study, our aim is to define risk factors and outcomes for patients with HC in allo-HSCT setting. METHODS: We retrospectively evaluated 249 allo-HSCTs performed between 2011 and 2016 in our center. RESULTS: HC was diagnosed in 98 patients (39%) at a median of 119 days (range, 5-580), and 91 (93%) of the patients had late onset disease...
July 4, 2018: Antiviral Therapy
Francis Ayuk, Dietrich W Beelen, Martin Bornhäuser, Matthias Stelljes, Tatjana Zabelina, Jürgen Finke, Guido Kobbe, Daniel Wolff, Eva-Maria Wagner, Maximilian Christopeit, Christoph Schmid, Hellmut Ottinger, Christoph Groth, Christoph Faul, Hartmut Bertz, Elena Rachlis, Christine Wolschke, Johannes Schetelig, Peter A Horn, Joannis Mytilineos, Martina Guellstorf, Reinhard Kelsch, Katharina Fleischhauer, Nicolaus Kröger, Wolfgang Bethge
Increasing donor-recipient HLA disparity is associated with negative outcomes of allogeneic hematopoietic stem cell transplantation (HSCT), but its comparative relevance amid non-HLA donor characteristics is not well established. We addressed this question in 3215 HSCTs performed between 2005 and 2013 in Germany for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Donors were HLA-matched related (MRD; n = 872) or unrelated (10/10 MUD, n = 1553) or HLA-mismatched unrelated (<10/10 MMUD, n = 790)...
July 24, 2018: Biology of Blood and Marrow Transplantation
Seyed M Hosseini-Moghaddam, Rohin Jayaram Krishnan, Hui Guo, Deepali Kumar
A growing number of publications have reported the outbreaks of post-transplant pneumocystis pneumonia (PJP). In most studies, the onset of PJP was beyond 6-12 months of prophylaxis. Cytomegalovirus (CMV) infection and allograft rejection have been repeatedly reported as probable risk factors for post-transplant PJP. In this systematic review and meta-analysis, we determined the pooled effect estimates of these 2 variables as risk factors. Data sources included PUBMED, MEDLINE-OVID, EMBASE-OVID, Cochrane Library, Networked Digital Library of Theses and Dissertations, World Health Organization, and Web of Science...
August 2018: Clinical Transplantation
S L Heatley, C G Mullighan, K Doherty, S Danner, G M O'Connor, U Hahn, J Szer, A Schwarer, K Bradstock, L C Sullivan, P G Bardy, A G Brooks
Natural killer cells are thought to influence the outcome of hematopoietic stem cell transplant (HSCT), impacting on relapse, overall survival, graft versus host disease and the control of infection, in part through the complex interplay between the large and genetically diverse killer immunoglobulin-like receptor (KIR) family and their ligands. This study examined the relationship between KIR gene content and clinical outcomes including the control of opportunistic infections such as cytomegalovirus in the setting of human leucocyte antigen (HLA)-matched sibling HSCT in an Australian cohort...
June 25, 2018: HLA
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