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Kun-Yin Qiu, Xiong-Yu Liao, Jian-Pei Fang, Hong-Gui Xu, Yang Li, Ke Huang, Dun-Hua Zhou
BACKGROUND: Invasive fungal disease(IFD) has a poor prognosis in children with hematological disorders after hematopoietic stem cell transplantation(HSCT). We assessed if drug combinations with different targets may improve the outcome. METHODS: Retrospective study to assess the outcome of combination antifungal therapy(CAT) for proven-probable IFD(PP-IFD) in children with hematological disorders after HSCT from January 2008 to June 2018. RESULTS: Over the 10-year period, 95 PP-IFD were diagnosed in paediatric recipients, median age of 5...
March 12, 2019: Transplant Infectious Disease: An Official Journal of the Transplantation Society
D H Lee, R A Zuckerman
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention and management of HSV in the pre- and post-transplant period. A majority of transplant recipients are seropositive for HSV-1 or 2. Compared with immunocompetent persons, SOT recipients shed HSV more frequently, have more severe clinical manifestations, and are slower to respond to therapy. Most HSV infection is diagnosed on clinical grounds, but patients may present with atypical lesions and/or other clinical manifestations...
March 12, 2019: Clinical Transplantation
Ravindra K Gupta, Sultan Abdul-Jawad, Laura E McCoy, Hoi Ping Mok, Dimitra Peppa, Maria Salgado, Javier Martinez-Picado, Monique Nijhuis, Annemarie M J Wensing, Helen Lee, Paul Grant, Eleni Nastouli, Jonathan Lambert, Matthew Pace, Fanny Salasc, Christopher Monit, Andrew Innes, Luke Muir, Laura Waters, John Frater, Andrew M L Lever, S G Edwards, Ian H Gabriel, Eduardo Olavarria
HIV-1 cure remains elusive with only one reported case a decade ago1,2 . Termed the 'Berlin patient', the individual underwent two allogeneic haematopoietic stem-cell transplantation (allo-HSCT) procedures using a donor with a homozygous mutation in the HIV coreceptor CCR5 (CCR5Δ32/Δ32) to treat his acute myeloid leukaemia. Total body irradiation was given with each HSCT. Critically, it is unclear which treatment or patient parameters contributed to this only documented case of long-term HIV remission. Here we show that HIV-1 remission may be possible with a less aggressive and toxic approach...
March 5, 2019: Nature
Nicolaus Kröger, Diderik-Jan Eikema, Linda Köster, Dietrich Beelen, Liesbeth C de Wreede, Jürgen Finke, Christian Koenecke, Dietger Niederwieser, Martin Bornhäuser, Stefan Schoenland, Victoria Potter, Christine Wolschke, Johan Maertens, Matthias Theobald, Guido Kobbe, Maija Itälä-Remes, Gerald Wulf, Peter Kahls, Edouard Forcade, Hildegard Greinix, Tamás Masszi, Ibrahim Yakoub-Agha, Yves Chalandon, Marie Robin
Myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and chronic myelomonocytic leukaemia (CMML) can progress to secondary acute myeloid leukaemia (sAML). We compared the outcome of 4214 sAML patients who received allogeneic haematopoietic stem cell transplantation (allo-HSCT) from an unrelated (62%) or human leucocyte antigen (HLA)-identical sibling donor (38%) according the underlying disease: MDS (n = 3541), CMML (n = 251) or MPN (n = 422). After a median follow up of 46·5 months, the estimated 3-year progression-free (PFS) and overall survival (OS) for the entire group was 36% (34-37%) and 41% (40-43%), respectively...
February 28, 2019: British Journal of Haematology
José Luis Piñana, Estela Giménez, María Dolores Gómez, Ariadna Pérez, Eva María González, Víctor Vinuesa, Juan Carlos Hernández-Boluda, Juan Montoro, Miguel Salavert, Mar Tormo, Paula Amat, Paula Moles, Carlos Carretero, Aitana Balaguer-Roselló, Jaime Sanz, Guillermo Sanz, Carlos Solano, David Navarro
OBJECTIVES: To date no definitive cut-off value for cytomegalovirus (CMV) DNA load in bronchoalveolar lavage (BAL) fluid specimens has been established to discriminate between CMV pneumonia and pulmonary CMV DNA shedding in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. METHODS: The current retrospective study is aimed at assessing the range of CMV DNA loads quantified in BAL fluid specimens from allo-HSCT patients with pneumonia in which different microorganisms were causally involved RESULTS: A total of 144 BAL specimens from 123 patients were included...
February 21, 2019: Journal of Infection
Amandine Fayard, Elisabeth Daguenet, Didier Blaise, Patrice Chevallier, Hélène Labussière, Ana Berceanu, Ibrahim Yakoub-Agha, Gérard Socié, Amandine Charbonnier, Felipe Suarez, Anne Huynh, Mélanie Mercier, Claude-Eric Bulabois, Bruno Lioure, Sylvain Chantepie, Yves Beguin, Jean-Henri Bourhis, Jean-Valère Malfuson, Laurence Clément, Régis Peffault de la Tour, Jérôme Cornillon
Several approaches have been developed to overcome historical barriers associated with poor outcomes in the setting of HLA-haploidentical allogeneic transplantation (HaploSCT). Here, we examine the outcome of patients with various hematological disorders undergoing HaploSCT with high-dose, post-transplantation cyclophosphamide. We performed a retrospective study on 381 patients from 30 centers between January 2013 and December 2015. At the last follow-up, a total of 1058 infectious episodes were diagnosed, affecting 90...
February 15, 2019: Bone Marrow Transplantation
Cláudia F Campos, Luís Leite, Paulo Pereira, Carlos Pinho Vaz, Rosa Branca, Fernando Campilho, Fátima Freitas, Dário Ligeiro, António Marques, Egídio Torrado, Ricardo Silvestre, João F Lacerda, António Campos, Cristina Cunha, Agostinho Carvalho
Background: Reactivation of latent human cytomegalovirus (CMV) in patients undergoing allogeneic stem-cell transplantation (HSCT) predisposes to several clinical complications and is therefore a major cause of morbidity and mortality. Although pentraxin-3 (PTX3) has been previously described to bind both human and murine CMV and mediate several host antiviral mechanisms, whether genetic variation in the PTX3 locus influences the risk of CMV infection is currently unknown. Methods: To dissect the contribution of genetic variation within PTX3 to the development of CMV infection, we analyzed described loss-of-function variants at the PTX3 locus in 394 recipients of HSCT and their corresponding donors and assessed the associated risk of CMV reactivation...
2019: Frontiers in Immunology
Takuto Takahashi, Maria A Pereda, Natasha Bala, Sairaman Nagarajan
BACKGROUND: Hematopoietic stem cell transplant (HSCT) can cure or alleviate a wide range of nonmalignant childhood conditions. However, few studies have examined longitudinal national trends of frequency or short-term complications of HSCT before 2006 when an HSCT became a reportable procedure by US law. By using a US nationally representative database, we conducted nationwide longitudinal analyses on demographics, in-hospital mortality, and short-term complications in nonmalignant HSCT from 2000 to 2012...
February 10, 2019: Pediatric Blood & Cancer
Alberto Talaya, Estela Giménez, José Luis Piñana, Eliseo Albert, Juan Carlos Hernández-Boluda, Ariadna Pérez, Ignacio Torres, Carlos Solano, David Navarro
It has been reported that low plasma cytomegalovirus (CMV) DNA loads are associated with an increased risk of overall mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Utilizing a conservative strategy for initiation of preemptive antiviral therapy (PET) (>1,500 IU/ml), we characterized the virological features of spontaneously-resolving episodes of CMV DNAemia and assessed their impact on mortality through the first year after transplantation. We reviewed the CMV DNA PCR results and clinical charts of 230 consecutive adult patients who underwent T-cell replete allo-HSCT at our center...
February 8, 2019: Journal of Medical Virology
Lucas C M Arruda, Ahmed Gaballa, Michael Uhlin
Although the impact of donor graft composition on clinical outcomes after hematopoietic stem cell transplantation (HSCT) has been studied, little is known about the role of intragraft γδ TCR repertoire on clinical outcomes following HSCT. Using a high-throughput sequencing platform, we sought to analyze the TCR γ-chain (TRG) repertoire of γδ T cells within donor stem cell grafts and address its potential impact on clinical response in the corresponding patients. A total of 20 peripheral blood stem cell grafts were analyzed, and donors were classified as CMV+/- The respective acute myeloid leukemia recipients were followed for disease relapse and acute graft-versus-host disease (aGvHD) development post-HSCT...
March 15, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
D A Shasheleva, A A Maschan, L N Shelikhova, U N Petrova, E E Kurnikova, O I Illarionova, E V Boyakova, G A Novichkova, M A Maschan
AIM: The main goal is to optimize hematopoietic stem cell transplantation (HSCT) approach among adolescents and young adults with paroxysmal nocturnal hemoglobinuria (PNH) by means of Graft-versus-host disease (GVHD) and post-transplant complications risk lowering. MATERIALS AND METHODS: We report our experience of HSCT from HLA-matched unrelated donors using TCR alfa/beta and CD19 depletion in 5 pts (1M/4F) with PNH, developed after successful immunosuppressive therapy (IST) of acquired aplastic anemia (AA)...
August 17, 2018: Terapevticheskiĭ Arkhiv
Jocelyne Piret, Guy Boivin
The prevention and treatment of human cytomegalovirus (HCMV) infections is based on the use of antiviral agents that currently target the viral DNA polymerase and that may cause serious side effects. The search for novel inhibitors against HCMV infection led to the discovery of new molecular targets, the viral terminase complex and the viral pUL97 kinase. The most advanced compounds consist of letermovir (LMV) and maribavir (MBV). LMV inhibits the cleavage of viral DNA and its packaging into capsids by targeting the HCMV terminase complex...
January 25, 2019: Antiviral Research
Qiuyu Li, Kai Wang, Wei Guo, Ming Lu
RATIONALE: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment for hematological malignancies. Common complications are opportunistic infections and graft-versus-host disease (GVHD). Cytomegalovirus (CMV) is one of the most common causes of opportunistic infections. PATIENT CONCERNS: A 30-year-old male was diagnosed with T-cell lymphoma after persistent cough and lymphadenopathy. Fever, abdominal pain, diarrhea, rash, and dyspnea occurred after HSCT...
January 2019: Medicine (Baltimore)
Tang-Her Jaing, Tsung-Yen Chang, Shih-Hsiang Chen, Yu-Chuan Wen, Ting-Jiuan Yu, Ching-Fen Lee, Chao-Ping Yang, Pei-Kwei Tsay
While preemptive therapy with ganciclovir (GCV) for cytomegalovirus (CMV) infection is used following allogeneic hematopoietic stem-cell transplantation (HSCT), risk factors for CMV infection in children undergoing HSCT are poorly understood.We studied CMV reactivation following allogeneic HSCT by retrospectively analyzing pediatric patients who received allogeneic HSCT and preemptive GCV therapy between 1998 and 2016. The level of viremia requiring preemptive GCV therapy was >1 CMV antigen-positive cells per 5 × 10 leukocytes during the antigenemia assay era and >1000 copies/mL in the polymerase chain reaction era...
January 2019: Medicine (Baltimore)
Jochen J Frietsch, Detlef Michel, Thomas Stamminger, Friederike Hunstig, Sebastian Birndt, Ulf Schnetzke, Sebastian Scholl, Andreas Hochhaus, Inken Hilgendorf
CMV associated tissue-invasive disease is associated with a considerable risk of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Recently, the terminase inhibitor letermovir (LMV) has been approved for prophylaxis of CMV infection in HSCT. We hereby report a 60-year-old female experiencing CMV reactivation after HSCT in a CMV seronegative donor-constellation. Due to ongoing elevated CMV viral load and drug-associated myelosuppression, which prevented ganciclovir therapy, treatment was replaced by foscarnet...
2019: Mediterranean Journal of Hematology and Infectious Diseases
Masahiro Ayano, Hiroshi Tsukamoto, Hiroki Mitoma, Yasutaka Kimoto, Mitsuteru Akahoshi, Yojiro Arinobu, Toshihiro Miyamoto, Takahiko Horiuchi, Hiroaki Niiro, Koji Nagafuji, Mine Harada, Koichi Akashi
BACKGROUND: The effectiveness of autologous haematopoietic stem cell transplantation (auto-HSCT) in treating severe systemic sclerosis (SSc) is established; however, the necessity of purified CD34+ cell grafts and the appropriate conditioning regimen remain unclear. This study aimed to compare the efficacy and safety of CD34-selected auto-HSCT with unmanipulated auto-HSCT to treat severe SSc. METHODS: This study was a post hoc analysis of a phase I/II clinical trial conducted in Japan...
January 22, 2019: Arthritis Research & Therapy
Yu-Lin Zhang, Yan Zhu, Qing Xiao, Li Wang, Lin Liu, Xiao-Hua Luo
Cytomegalovirus (CMV) infection and primary disease relapse remain challenging problems after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We sought to assess the association between CMV infection and disease relapse after transplantation. PubMed, EMBASE, the Cochrane Library, SCI, and Chinese Biomedicine Databases were searched up to July 1, 2018, for all studies that investigate pre-transplant CMV serostatus, CMV replication, and primary disease relapse in allo-HSCT patients with hematologic malignancies...
January 21, 2019: Annals of Hematology
Mizuki Watanabe, Junya Kanda, Masakatsu Hishizawa, Tadakazu Kondo, Kouhei Yamashita, Akifumi Takaori-Kondo
BACKGROUND: Systemic steroid is used to treat various transplant-related complications after allogenic hematopoietic stem cell transplantation (allo-HSCT). However, measures to evaluate its impact on infections are still limited. Hence, we examined the cumulative steroid dose used within 30 days after transplant as a predictor of future risk of infections. METHODS: This study included 226 patients who underwent their first allo-HSCT at Kyoto University Hospital between 2005 and 2015...
January 17, 2019: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Sam Van Hecke, Bas Calcoen, Katrien Lagrou, Johan Maertens
Cytomegalovirus (CMV) manifestations remain important complications after allogeneic hematopoietic stem cell transplantation (HSCT), even in the current era. Unfortunately, available anti-CMV agents, mainly viral polymerase inhibitors, have a substantial risk of myelosuppression and nephrotoxicity. Letermovir, a novel anti-CMV drug that targets the viral terminase complex, has recently been approved for the prevention of clinically significant CMV infection in adult CMV seropositive hematopoietic stem cell transplantation recipients...
January 15, 2019: Future Microbiology
Beatriz Guglieri-Lopez, Alejandro Perez-Pitarch, Irene Garcia-Cadenas, Estela Gimenez, Pere Barba, Nuria Rabella, Juan Carlos Hernandez-Boluda, Laura Fox, David Valcarcel, Albert Esquirol, Rafael Ferriols-Lisart, Jorge Sierra, Carlos Solano, David Navarro, Rodrigo Martino, José Luis Piñana
The current study evaluates the clinical effect of sirolimus exposure on the occurrence of cytomegalovirus (CMV) DNAemia necessitating preemptive antiviral therapy. A total of 167 consecutive recipients of reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) who received sirolimus- and tacrolimus-based graft-versus-host disease (GVHD) prophylaxis and whose CMV serostatus was positive for donors and/or recipients were included in this multicenter retrospective study...
January 10, 2019: Biology of Blood and Marrow Transplantation
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