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Chronic graft versus host

Anke Theil, Carmen Wilhelm, Matthias Kuhn, Andreas Petzold, Sebastian Tuve, Uta Oelschlägel, Andreas Dahl, Martin Bornhäuser, Ezio Bonifacio, Anne Eugster
T regulatory cell (Treg) therapy has been exploited in autoimmune disease, solid organ transplantation and in efforts to prevent or treat graft-versus-host disease (GvHD). However, our knowledge on in vivo persistence of transfused Treg is limited. Whether Treg transfusion leads to notable changes in the overall Treg repertoire and or whether longevity of Treg in the periphery is restricted to certain clones is unknown. Here we use T cell receptor alpha chain sequencing (TCRα-NGS) to monitor changes in the repertoire of Treg upon polyclonal expansion and after subsequent adoptive transfer...
October 24, 2016: Clinical and Experimental Immunology
Changcheng Zheng, Baolin Tang, Xiaoyu Zhu, Xuhan Zhang, Lei Zhang, Liangquan Geng, Huilan Liu, Zimin Sun
The aim of this study is to investigate the impact of pre-engraftment bloodstream infections (BSIs) on the outcomes in acute leukemia patients undergoing myeloablative cord blood transplantation (CBT). A total of 226 acute leukemia patients who received unrelated CBT were enrolled in this study, and all these patients received an intensified myeloablative conditioning without ATG. Pre-engraftment BSIs occurred in 72 patients (31.9 %), and the median time of onset was 4.5 days after cord blood infusion, BSIs of gram-negative bacilli, and gram-positive cocci comprised of 63...
October 22, 2016: Annals of Hematology
Paul J Martin, Wenhong Fan, Barry E Storer, David M Levine, Lue Ping Zhao, Edus H Warren, Mary E D Flowers, Stephanie J Lee, Paul A Carpenter, Michael Boeckh, Sangeeta Hingorani, Li Yan, Qiang Hu, Leah Preus, Song Liu, Stephen Spellman, Xiaochun Zhu, Marcelo Pasquini, Philip McCarthy, Daniel Stram, Xin Sheng, Loreall Pooler, Christopher A Haiman, Lara Sucheston-Campbell, Theresa Hahn, John A Hansen
Previous studies have identified single-nucleotide polymorphisms (SNPs) associated with the risk of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). The current study determined whether these associations could be replicated in large cohorts of donors and recipients. Each SNP was tested with cohorts of patients having the same donor type (HLA-matched related, unrelated or both) reported in the original publication, and testing was limited to the same genome (recipient or donor) and genetic model (dominant, recessive or allelic) reported in the original study...
October 6, 2016: Blood
Annalisa Ruggeri, Yuqian Sun, Myriam Labopin, Andrea Bacigalupo, Francesca Lorentino, William Arcese, Stella Santarone, Zafar Gülbas, Didier Blaise, Giuseppe Messina, Ardeshi Ghavamzadeh, Florent Malard, Benedetto Bruno, Jose Luis Diez-Martin, Yener Koc, Fabio Ciceri, Mohamad Mohty, Arnon Nagler
Severe graft-versus-host-disease is a major barrier for non T-cell-depleted haploidentical stem cell transplantation and there is no consensus on the optimal GVHD prophylaxis. This study compared the two most commonly used graft-versus-host-disease prophylaxis regimens (post-transplant-cyclophosphamide-based (PTCY) versus the anti-thymocyte-globulin-based (ATG)) in adults with acute myeloid leukemia reported to the european society for blood and bone marrow transplantation. 308 patients were analyzed, 193 received PTCY and 115 ATG as anti- graft-versus-host-disease prophylaxis...
October 6, 2016: Haematologica
Jeremy Woodward, Effrossyni Gkrania-Klotsas, Dinakantha Kumararatne
Chronic infection with Norovirus is emerging as a significant risk for patients with immunodeficiency - either primary or secondary to therapeutic immunosuppression. Patients with primary immunodeficiency present a range of pathological responses to Norovirus infection. Asymptomatic infections occur and differentiating viral carriage or prolonged viral shedding after self-limiting infection from infection causing protracted diarrhoea can be challenging due to relatively mild pathological changes that may mimic other causes of diarrhoea in such patients (for instance pathogenic bacteria or parasites or graft-versus-host disease)...
October 18, 2016: Clinical and Experimental Immunology
Aline Clavert, Zinaida Peric, Eolia Brissot, Florent Malard, Thierry Guillaume, Jacques Delaunay, Viviane Dubruille, Steven Le Gouill, Beatrice Mahe, Thomas Gastinne, Nicolas Blin, Jean-Luc Harousseau, Philippe Moreau, Noel Milpied, Mohamad Mohty, Patrice Chevallier
Late complications (LC) and quality of life (QOL) were analyzed in 110 adult patients who underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) and were alive for more than two years after allo-SCT. Overall survival of these patients was 93% (95%CI, 88-99%) and 81% (95%CI, 71-94%) at 5 and ten years, respectively. The primary cause of death was a recurrence of primary malignancy. With a median follow-up of 4.6 years (range, 2-12.1), chronic graft versus host disease (cGVHD) was the most prevalent late effect with a cumulative incidence (CI) of 66% (95%CI, 57-74) at ten years...
October 14, 2016: Biology of Blood and Marrow Transplantation
J Kanda, Y Morishima, S Terakura, A Wake, N Uchida, S Takahashi, Y Ono, Y Onishi, H Kanamori, N Aotsuka, Y Ozawa, H Ogawa, T Sakura, K Ohashi, T Ichinohe, K Kato, Y Atsuta, T Teshima, M Murata
The effect of graft-versus-host disease (GVHD) on transplant outcomes after unrelated cord blood transplantation (UCBT) has not been fully elucidated. We analyzed the impact of acute and chronic GVHD on outcomes in adult patients with acute leukemia or myelodysplastic syndrome who underwent their first UCBT (n=2558). The effect of GVHD on outcomes was analyzed after adjusting for other significant variables. The occurrence of GVHD was treated as a time-dependent covariate. The occurrence of grade 1-2 or 3-4 acute GVHD was significantly associated with a lower relapse rate...
October 17, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Imke H Bartelink, Arief Lalmohamed, Elisabeth M L van Reij, Christopher C Dvorak, Rada M Savic, Juliette Zwaveling, Robbert G M Bredius, Antoine C G Egberts, Marc Bierings, Morris Kletzel, Peter J Shaw, Christa E Nath, George Hempel, Marc Ansari, Maja Krajinovic, Yves Théorêt, Michel Duval, Ron J Keizer, Henrique Bittencourt, Moustapha Hassan, Tayfun Güngör, Robert F Wynn, Paul Veys, Geoff D E Cuvelier, Sarah Marktel, Robert Chiesa, Morton J Cowan, Mary A Slatter, Melisa K Stricherz, Cathryn Jennissen, Janel R Long-Boyle, Jaap Jan Boelens
BACKGROUND: Intravenous busulfan combined with therapeutic drug monitoring to guide dosing improves outcomes after allogeneic haemopoietic cell transplantation (HCT). The best method to estimate busulfan exposure and optimum exposure in children or young adults remains unclear. We therefore assessed three approaches to estimate intravenous busulfan exposure (expressed as cumulative area under the curve [AUC]) and associated busulfan AUC with clinical outcomes in children or young adults undergoing allogeneic HCT...
October 13, 2016: Lancet Haematology
Gloria B Chiu, Christos Theophanous, John A Irvine
PURPOSE: To report a case of persistent epithelial defects in a patient with ocular chronic graft-versus-host disease that required coordinated modulation of systemic immunosuppressive treatment and overnight wear of Prosthetic Replacement of the Ocular Surface Ecosystem (BostonSight PROSE, Needham, MA) devices to achieve ocular surface healing. CASE REPORT: The case of a 38-year-old male patient who presented with a 2-year history of ocular chronic graft-versus-host disease, ocular burning, pain, light sensitivity, and a 3-week history of bilateral corneal epithelial defects is presented...
October 12, 2016: Optometry and Vision Science: Official Publication of the American Academy of Optometry
Satoshi Iyama, Tsutomu Sato, Hirofumi Ohnishi, Yuji Kanisawa, Shuichi Ohta, Takeshi Kondo, Akio Mori, Yutaka Tsutsumi, Hiroyuki Kuroda, Yasutaka Kakinoki, Satoshi Yamamoto, Tohru Takahashi, Motohiro Shindo, Yoshihiro Torimoto, Kazuya Sato, Hiroshi Iwasaki, Yoshihito Haseyama, Kyuhei Kohda, Yasuhiro Nagamachi, Yasuo Hirayama, Hajime Sakai, Yasuji Hirata, Takashi Fukuhara, Hiroshi Ikeda, Masayoshi Kobune, Junji Kato, Mitsutoshi Kurosawa
BACKGROUND: Mogamulizumab, a defucosylated humanized monoclonal antibody targeting C-C chemokine receptor 4, recently became available for the treatment of adult T-cell leukemia/lymphoma (ATL). We conducted a multicenter retrospective study of the efficacy of mogamulizumab in ATL treatment in patients on Hokkaido Island, Japan. MATERIALS AND METHODS: A total of 125 patients with ATL treated from January 2010 to December 2014 in 20 hospitals affiliated with the Hokkaido Hematology Study Group were enrolled in the present retrospective study...
September 17, 2016: Clinical Lymphoma, Myeloma & Leukemia
Ryo Ishida, Akira Shimizu, Takashi Kitani, Mayumi Nakata, Noriyoshi Ota, Hiroshi Kado, Yayoi Shiotsu, Mami Ishida, Keiichi Tamagaki
A 30-year-old woman with myelodysplastic syndrome underwent allogeneic hematopoietic stem cell transplantation (HSCT) derived from her HLA-matched sister six years previously. She received preconditioning total body irradiation with renal shielding and was subsequently administered cyclosporin A (CyA) as prophylaxis against graft-versus-host disease (GVHD). Four months after HSCT, asymptomatic proteinuria and glomerular hematuria developed during CyA tapering without obvious extrarenal involvements of GVHD, and persisted for six years...
2016: Internal Medicine
Leylagul Kaynar, Koray Demir, Esra Ermiş Turak, Çiğdem Pala Öztürk, Gökmen Zararsız, Zeynep Burçin Gönen, Selma Gökahmetoğlu, Serdar Şıvgın, Bülent Eser, Yavuz Köker, Musa Solmaz, Ali Ünal, Mustafa Çetin
INTRODUCTION: The use of αβ+ T-cell-depleted grafts is a novel approach to prevent graft failure, graft-versus-host disease (GVHD), and non-relapse mortality (NRM) in patients undergoing haploidentical hematopoietic stem cell transplantation. PATIENT AND METHOD: Thirty-four patients with acute leukemia and lacking a match donor were treated with αβ T-cell-depleted allografts from haploidentical family donors. A total of 24 patients had acute myeloid leukemia (AML) and 10 had acute lymphoblastic leukemia...
October 10, 2016: Hematology (Amsterdam, Netherlands)
William Nigel Patton, Ian Nivison-Smith, Peter Bardy, Anthony Dodds, David Ma, Peter John Shaw, John Kwan, Leonie Wilcox, Andrew Butler, John M Carter, Hilary Blacklock, Jeffrey Szer
A previous study found that platelet recovery and mortality were worse in recipients of myeloablative bone marrow transplants where graft transit times were longer than 20 hours. This retrospective study of unrelated myeloablative allogeneic transplantation performed within Australia and NZ analysed transplant outcomes according to graft transit times. Of evaluable cases (n=233), 76 (33%) grafts were sourced from bone marrow (BM) and 157 (67%) from peripheral blood. Grafts sourced from Australia and NZ (47% of total) were associated with a median transit time of 6 hours versus 32 hours for overseas sourced grafts (53% of total)...
October 4, 2016: Biology of Blood and Marrow Transplantation
Hong-Hua Li, Fei Li, Chun-Ji Gao, Wen-Rong Huang, Jian Bo, Li-Ping Dou, Li-Li Wang, Yu Jing, Lu Wang, Wen-Jun Li, Li Yu, Dai-Hong Liu
The features of graft-versus-host disease (GVHD) were compared between patients who underwent myeloablative conditioning and received a peripheral blood stem cell transplant (PBSCT) from either a haploidentical donor (HID) or a matched sibling donor (MSD) during the same period of time. The HID group included more patients with advanced disease. Both groups received the same GVHD prophylaxis with the addition of antithymoglobulin (ATG) in HID group. Higher cumulative incidences (CI) of acute GVHD grade 2-4 (35·1% vs...
October 7, 2016: British Journal of Haematology
Kenneth R Cooke, Leo Luznik, Stefanie Sarantopoulos, Frances T Hakim, Madan Jagasia, Daniel H Fowler, Marcel R M van den Brink, John A Hansen, Robertson Parkman, David B Miklos, Paul J Martin, Sophie Paczesny, Georgia Vogelsang, Steven Pavletic, Jerome Ritz, Kirk R Schultz, Bruce R Blazar
Chronic graft-versus-host disease (GVHD) is the leading cause of late, non-relapse, mortality and disability in allogeneic hematopoietic cell transplantation (HCT) patients and a major obstacle to improving outcomes. Chronic GVHD biology remains enigmatic, but understanding the underpinnings of the immunologic mechanisms responsible for the initiation and progression of disease is fundamental to developing effective prevention and treatment strategies. The goals of this task force review are as follows: • Summarize the current "state-of-the-science" regarding pathogenic mechanisms of chronic GVHD and critical knowledge gaps...
October 3, 2016: Biology of Blood and Marrow Transplantation
Yutaro Hino, Noriko Doki, Yasushi Senoo, Noritaka Sekiya, S Kurosawa, Satoshi Tsuboi, Kazuteru Ohashi
Nocardiosis is a rare bacterial infection occurring mainly in patients with deficient cell-mediated immunity. Although disseminated nocardiosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a rare complication, it is associated with high mortality. Moreover, after allo-HSCT, nocardiosis may be mistaken for other bacterial or fungal infections because clinical and radiographic findings of pulmonary, cerebral, and cutaneous nocardiosis lesions are non-specific. Here, we report a case of disseminated nocardiosis (caused by Nocardia abscessus) with skin, pulmonary, liver, lymph node, and multiple brain abscesses in a patient after allo-HSCT...
October 1, 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Stavroula Masouridi-Levrat, Federico Simonetta, Yves Chalandon
Bone marrow failure (BMF) syndromes are severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this paper, we distinguish two different entities, the graft failure (GF) and the poor graft function (PGF), and we review the current understanding of the interactions between the immune and hematopoietic compartments in these conditions. We first discuss how GF occurs as the result of classical alloreactive immune responses mediated by residual host cellular and humoral immunity persisting after conditioning and prevented by host and donor regulatory T cells...
2016: Frontiers in Immunology
Frances T Hakim, Sarfraz Memon, Ping Jin, Matin M Imanguli, Huan Wang, Najibah Rehman, Xiao-Yi Yan, Jeremy Rose, Jacqueline W Mays, Susan Dhamala, Veena Kapoor, William Telford, John Dickinson, Sean Davis, David Halverson, Haley B Naik, Kristin Baird, Daniel Fowler, David Stroncek, Edward W Cowen, Steven Z Pavletic, Ronald E Gress
Although chronic graft-versus-host disease (CGVHD) is the primary nonrelapse complication of allogeneic transplantation, understanding of its pathogenesis is limited. To identify the main operant pathways across the spectrum of CGVHD, we analyzed gene expression in circulating monocytes, chosen as in situ systemic reporter cells. Microarrays identified two interrelated pathways: 1) IFN-inducible genes, and 2) innate receptors for cellular damage. Corroborating these with multiplex RNA quantitation, we found that multiple IFN-inducible genes (affecting lymphocyte trafficking, differentiation, and Ag presentation) were concurrently upregulated in CGVHD monocytes compared with normal subjects and non-CGVHD control patients...
September 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Sarvari Velaga, Christina Alter, Ulrike Dringenberg, Christina T Thiesler, Sandra Kuhs, Sven Olek, Sya N Ukena, Anke Franzke
OBJECTIVE: Recent clinical trials have shown the high potential of regulatory T cells (Tregs) in prevention of acute and chronic graft-versus-host disease (GvHD) following hematopoietic stem cell transplantation but immune interventions require high Treg cell numbers. With respect to limited natural occurrence, development and optimization of large-scale expansion protocols of clinical-grade Tregs are essential if considered for therapeutic use. METHODS: We compared different clinical grade large-scale expansion protocols for repetitive transfer of high Treg cell numbers in clinical trials for the prevention of acute and/or chronic GvHD...
September 27, 2016: Experimental Hematology
E M Weissinger, C Human, J Metzger, L Hambach, D Wolf, H T Greinix, A M Dickinson, W Mullen, D Jonigk, Z Kuzmina, H Kreipe, P Schweier, O Böhm, I Türüchanow, D Ihlenburg-Schwarz, J Raad, A Durban, M Schiemann, C Könecke, H Diedrich, E Holler, G Beutel, J Krauter, A Ganser, M Stadler
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be curative, but is associated with significant morbidity and mortality. Chronic graft-versus-host disease (cGvHD), characterized by inflammation and fibrosis of multiple target organs, considerably contributes to the morbidity and mortality even years after allo-HSCT. Diagnosis of cGvHD is based on clinical features and histology of biopsies. Here, we report the generation of a urinary cGvHD-specific proteome-pattern (cGvHD_MS14) established by capillary electrophoresis-mass spectrometry to predict onset and severity of cGvHD as an unbiased laboratory test...
September 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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