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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
OBJECTIVES: Platelet-derived growth factor receptor-alpha (PDGFRa) is a critical receptor for CMV entry into cells, leading to subsequent infection. This trial tested whether PDGFRa inhibition by nilotinib could prevent CMV infection in patients after allo-HSCT. METHODS: Nilotinib (200 mg/day) was given continuously after engraftment, and plasma CMV DNA levels were monitored weekly. The primary endpoint was successful prophylaxis of cytomegalovirus 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 16, 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 23, 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...
June 29, 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 (PBPK) 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)...
May 29, 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
Jan M Middeke, Frederike Kollinger, Henning Baldauf, Friedrich Stölzel, Martin Wermke, Malte von Bonin, Katja Sockel, Cornelia S Link, Raphael Teipel, Christoph Röllig, Christian Thiede, Uwe Platzbecker, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig
Despite recent advances, allogeneic hematopoietic stem cell transplantation (allo-HSCT) continues to be accompanied by a high rate of morbidity and mortality. Several scores have been developed to predict outcome after allo-HSCT. The recently revised Pretransplant Assessment of Mortality (PAM) score is based on patient age, donor type, disease risk, cytomegalovirus (CMV) serostatus of patient and donor, and forced expiratory volume in 1 second (FEV1 ). The aim of this study was to analyze the predictive power of the PAM score in an independent large cohort of patients with acute myelogenous leukemia (AML)...
May 21, 2018: Biology of Blood and Marrow Transplantation
Y Q Sun, X J Huang, L P Xu, X H Zhang, C H Yan, K Y Liu, Y Wang
Objective: To investigate the impact of mycophenolate mofetil (MMF) prophylaxis duration on acute graft-versus-host disease (aGVHD) after haploidentical stem cell transplantation (haplo-HSCT) using 'Beijing Protocol'. Methods: Adult patients (≥14 years) received haplo-HSCT in Peking University Institute of Hematology from Sep, 2016 to Mar, 2017 were retrospectively reviewed if they fulfilled the criterias: ①diagnosed with hematological maligancies; ②standard-risk status at haplo-HSCT. A total of 237 patients [including 102 patients with long MMF duration (defined as started on day -9 with 100 mg/d, adjusted to 500 mg/d from day +30 and discontinued on day +45 to +60 or occurrence of CMV/EBV reactivation or late-onset hemorrhagic cytitis), and 135 patients with short MMF duration (defined as started on day -9 with 500 mg/d and discontinued on the day achieved neutrophil engraftment)] were reviewed...
April 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Bilio Paouri, Alexandra Soldatou, Eftihia Petrakou, Maria Theodosaki, Charalampos Tsentidis, Katerina Kaisari, Christina Oikonomopoulou, Minos Matsas, Eugenios Goussetis
Pediatric HSCT recipients are at high risk for CMV reactivation due to their immature immune system and therapy following transplantation. Reconstitution of CMV-specific T-cell immunity is associated with control and protection against CMV. The clinical utility of monitoring CMV-specific CMI to predict CMV viremia in pediatric HSCT patients using the Quantiferon-CMV (QIAGEN® ) test was investigated prospectively. Thirty-seven pediatric allogeneic HSCT recipients were enrolled from 3/2010-6/2012. CMV viremia was detected via weekly real-time PCR...
August 2018: Pediatric Transplantation
Jean-Hugues Dalle, Adriana Balduzzi, Peter Bader, Arjan Lankester, Isaac Yaniv, Jacek Wachowiak, Anna Pieczonka, Marc Bierings, Akif Yesilipek, Petr Sedlaçek, Marianne Ifversen, Sabina Sufliarska, Jacek Toporski, Evgenia Glogova, Ulrike Poetschger, Christina Peters
Allogeneic hematopoietic stem cell transplantation (HSCT) is beneficial for pediatric patients with relapsed or (very) high-risk acute lymphoblastic leukemia (ALL) in remission. A total of 1115 consecutive patients were included in the ALL SCT 2003 BFM study and the ALL SCT 2007 I-BFM study and were stratified according to relapse risk (standard versus high versus very high risk of relapse) and donor type (matched sibling versus matched donor versus mismatched donor). A total of 148 patients (60% boys; median age, 8...
May 14, 2018: Biology of Blood and Marrow Transplantation
Jeff K Davies, Lisa L Brennan, John R Wingard, Christopher R Cogle, Neena Kapoor, Ami J Shah, Bimalangshu R Dey, Thomas R Spitzer, Marcos de Lima, Laurence J Cooper, Peter F Thall, Richard E Champlin, Lee M Nadler, Eva C Guinan
Purpose: Allogeneic hematopoietic stem-cell transplantation (HSCT) is a curative treatment for many hematologic cancers. Use of haploidentical (mismatched) donors increases HSCT availability but is limited by severe graft-versus-host disease (GvHD) and delayed immune reconstitution. Alloanergization of donor T cells is a simple approach to rebuild immunity while limiting GvHD after haploidentical HSCT, but the optimal T-cell dose and impact on immune reconstitution remain unknown. Experimental Design: We performed a multicenter phase I trial of alloanergized donor lymphocyte infusion (aDLI) after CD34-selected myeloablative haploidentical HSCT...
May 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Kara Robertson, Stephen Couban, Desmond Leddin, Imran Ahmad, Lori Connors
Background: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency characterized by recurrent life-threatening bacterial and fungal infections, granuloma formation and intestinal disease. This disease is caused by defects in NADPH oxidase, which result in the inability of phagocytes (neutrophils, monocytes and macrophages) to destroy certain microbes. The only established curative therapy for CGD is hematopoietic stem cell transplantation. Case presentation: A 23-year-old Caucasian male with X-linked chronic granulomatous disease underwent a reduced-intensity conditioning, matched unrelated donor peripheral blood stem cell transplant, after which he was started on tacrolimus and mycophenolate for graft-versus-host disease prophylaxis...
2018: Allergy, Asthma, and Clinical Immunology
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