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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...
August 16, 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
Ying-Hong Wang, Dapeng Chen, Georgy Hartmann, Carolyn R Cho, Karsten Menzel
Letermovir is a human cytomegalovirus (CMV) terminase inhibitor for the prophylaxis of CMV infection in allogeneic hematopoietic stem-cell transplant (HSCT) recipients. In vitro, letermovir is a time-dependent inhibitor and an inducer of cytochrome P450 (CYP)3A, and an inhibitor of CYP2C8 and organic anion transporting polypeptide (OATP)1B. A stepwise approach was taken to qualify the interaction model of an existing letermovir physiologically based pharmacokinetic model to predict letermovir interactions with CYP3A and OATP1B...
June 14, 2018: Clinical Pharmacology and Therapeutics
Carlos Solano, Estela Giménez, Eliseo Albert, Eva María Mateo, Montserrat Gómez, Rosa Goterris, Ariadna Pérez, Paula Amat, Juan Carlos Hernández-Boluda, Marc Poch, José Luis Piñana, David Navarro
To gauge the risk of delaying initiation of prophylaxis with letermovir from the time of donor infusion to prevent CMV infection in allo-HSCT recipients we investigated the clinical outcomes of CMV DNAemia episodes occurring before engraftment, and compared to that of episodes developing after engraftment (up to day +365). A total of 197 consecutive adult patients were included. Plasma CMV DNA load was monitored by real-time PCR assays [limit of detection: 31 IU/ml]. A total of 150 out of 197 patients had CMV DNAemia (cumulative incidence of 77%; 95% CI, 73-81%), and 38 out of the 197 patients developed it before engraftment (cumulative incidence, 19%; 95% CI, 10-30...
June 13, 2018: Bone Marrow Transplantation
Tetsushi Yoshikawa
Two of the four betaherpesviruses, Cytomegalovirus (CMV) and human herpesvirus 6B (HHV-6B), play an important role in opportunistic infections in hematopoietic stem cell transplant (HSCT) recipients. These viruses are ubiquitous in humans and can latently infect mononuclear lymphocytes, complicating the diagnosis of the diseases they cause. Although the detection of viral DNA in a patient's peripheral blood by real-time PCR is widely used for monitoring viral infection, it is insufficient for the diagnosis of virus-associated disease...
2018: Advances in Experimental Medicine and Biology
I P Lodding, C da Cunha Bang, S S Sørensen, F Gustafsson, M Iversen, N Kirkby, M Perch, A Rasmussen, H Sengeløv, A Mocroft, J D Lundgren
Background: Transplant recipients presenting with cytomegalovirus (CMV) disease at the time of diagnosis of CMV DNAemia pose a challenge to a preemptive CMV management strategy. However, the rate and risk factors of such failure remain uncertain. Methods: Solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) recipients with a first episode of CMV polymerase chain reaction (PCR) DNAemia within the first year posttransplantation were evaluated (n = 335)...
May 2018: Open Forum Infectious Diseases
José Luis Piñana, María Dolores Gómez, Ariadna Pérez, Silvia Madrid, Aitana Balaguer-Roselló, Estela Giménez, Juan Montoro, Eva María González, Víctor Vinuesa, Paula Moles, Juan Carlos Hernández-Boluda, Miguel Salavert, Marisa Calabuig, Guillermo Sanz, Carlos Solano, Jaime Sanz, David Navarro
Risk factors (RFs) and mortality data of community-acquired respiratory virus (CARVs) lower respiratory tract disease (LRTD) with concurrent pulmonary co-infections in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is scarce. From January 2011 to December 2017, we retrospectively compared the outcome of allo-HSCT recipients diagnosed of CARVs LRTD mono-infection (n = 52, group 1), to those with viral, bacterial, or fungal pulmonary CARVs LRTD co-infections (n = 15, group 2; n = 20, group 3, and n = 11, group 4, respectively), and with those having bacterial pneumonia mono-infection (n = 19, group 5)...
August 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Elisabetta Metafuni, Patrizia Chiusolo, Simona Sica, Luca Laurenti, Stefania Bregante, Maria Teresa Van Lint, Alida Dominietto, Emanuele Angelucci, Andrea Bacigalupo
We studied 97 patients who developed cytomegalovirus (CMV) viremia following an allogeneic hemopoietic stem cell transplant (HSCT) between 2010 and 2015, treated with foscarnet, with the aim of assessing efficacy and safety. The donor was unrelated in 30 patients (UD) and a family HLA-haploidentical donor (HAPLO) in 67 patients: the former (UD) received a prophylaxis for graft-versus-host disease (GvHD), based on antithymocyte globulin (ATG); the latter (HAPLO) received GvHD prophylaxis, based on post-transplant cyclophosphamide (PT-CY)...
May 24, 2018: Bone Marrow Transplantation
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