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Hidekazu Nishikii, Byung-Su Kim, Yasuhisa Yokoyama, Yan Chen, Jeanette Baker, Antonio Pierini, Maite Alvarez, Melissa Mavers, Kristina Maas-Bauer, Yuqiong Pan, Shigeru Chiba, Robert S Negrin
CD4(+)Foxp3(+) regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft versus host disease (GVHD) in murine models of allogeneic hematopoietic stem cell transplantation (HCT). We recently demonstrated that a single treatment of the agonistic antibody to DR3 (Death receptor 3, αDR3) to donor mice resulted in the expansion of donor derived Treg and prevented acute GVHD, although the precise role of DR3 signaling in GVHD has not been elucidated...
October 19, 2016: Blood
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
Scott N Furlan, Benjamin Watkins, Victor Tkachev, Sarah Cooley, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, Daniel J Hunt, John B Schell, Katie Zeleski, Alison Yu, Cindy Giver, Edmund Waller, Jeffrey S Miller, Bruce R Blazar, Leslie S Kean
One of the central challenges of transplantation is the development of alloreactivity despite the use of multi-agent immunoprophylaxis. Effective control of this immune-suppression-resistant T cell activation represents one of the key unmet needs in the fields of both solid organ and hematopoietic stem cell transplant (HCT). To address this unmet need, we have used a highly-translational non-human primate model to interrogate the transcriptional signature of T cells during Breakthrough Acute GVHD that occurs in the setting of clinically-relevant immune suppression and compared this to the Hyperacute GVHD, that develops in unprophylaxed or sub-optimally prophylaxed transplant recipients...
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
Juan Gea-Banacloche, Krishna Komanduri, Paul Carpenter, Sophie Paczesny, Stefanie Sarantopoulos, Jo-Anne Young, Nahed El Kassar, Robert Q Le, Kirk Schultz, Linda M Griffith, Bipin Savani, John R Wingard
Immune reconstitution following hematopoietic stem cell transplantation (HCT) beyond one year is not completely understood. Many transplant recipients who are free of graft versus host disease (GVHD) and not receiving any immunosuppression more than a year after transplant seem to be able to mount appropriate immune responses to common pathogens and respond adequately to immunizations. However, two large registry studies over the last two decades seem to indicate that infection is a significant cause of late mortality in some patients, even in the absence of concomitant GVHD...
October 14, 2016: Biology of Blood and Marrow Transplantation
Raziyeh Tootoonchian, Fatemeh Pak, Ali M Ardekani, Nasrin Sehati, Manuchehr Abedi-Valugerdi, Parviz Kokhaei
The present study tried to explain CD56+ lymphocyte cells activities and possible prognostic role of these cells in Graft-Versus-Host-Disease (GVHD). The role of IL-12 activation and function is of interest in this study. Peripheral blood samples of 51 Hematopoietic Stem Cell Transplantation (HSCT) recipients collected at before (day -8) and after (days 7 and 14). PBMC were collected by Ficoll separation and analyzed by Flow Cytometry using triple antibody (CD45-PerCP, CD56-FITC, and CD69-PE staining and control antibody...
October 14, 2016: Transplant Immunology
Yifeng Cai, Shoubao Ma, Yuejun Liu, Huanle Gong, Qiao Cheng, Bo Hu, Yan Wu, Xiao Yu, Chen Dong, Kai Sun, Depei Wu, Haiyan Liu
The role of IL-17 and IL-17-producing CD4(+) T cells in acute graft-versus-host disease (GVHD) has been controversial in recent mouse and human studies. We carried out studies in a murine acute GVHD model of fully major histocompatibility complex-mismatched myeloablative bone marrow transplantation. We showed that donor wild-type CD4(+) T cells exacerbated acute GVHD compared with IL-17(-/-) CD4(+) T cells, while IL-17 reduced the severity of acute GVHD. The augmentation of acute GVHD by transferred donor IL-17-producing CD4(+) T cells was associated with increased Th1 responses, while IL-17 decreased the percentages of Th1 cells in the GVHD target organs...
October 17, 2016: Cellular & Molecular Immunology
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
Bruno Sangiorgi, Rodrigo Alexandre Panepucci
In the last decade, the immunomodulatory properties of mesenchymal stromal cells (MSCs) have attracted a lot of attention, due to their potential applicability in the treatment of graft-versus-host disease (GVHD), a condition frequently associated with opportunistic infections. The present review addresses how Pathogen-Associated Molecular Patterns (PAMPS) modulate the immunosuppressive phenotype of human MSCs by signaling through Toll-like receptors (TLRs). Overall, we observed that regardless of the source tissue, human MSCs express TLR2, TLR3, TLR4, and TLR9...
2016: Stem Cells International
Giovanna Lucchini, Andre Manfred Willasch, Julia Daniel, Jan Soerensen, Andrea Jarisch, Shahrzad Bakhtiar, Eva Rettinger, Joerg Brandt, Thomas Klingebiel, Peter Bader
CLS involves sudden loss of intravascular fluids into the interstitial spaces. CLS was described as a possible complication after SCT. Few studies report the incidence of CLS in pediatric populations. We aimed to assess CLS incidence, its risk factors, and impact on the survival. The clinical charts of patients <18 years of age transplanted at our institution between 2002 and 2012 were reviewed. CLS was defined by weight gain >3% in 24 hours and positive intake balance despite furosemide administration...
October 13, 2016: Pediatric Transplantation
E Yu, H Ueta, H Kimura, Y Kitazawa, Y Sawanobori, K Matsuno
Graft-versus-host disease (GvHD) following liver transplantation (LT) is a rare but serious complication, with no presently available animal model and no preventive measure. To develop a rat LT-GvHD model, we preconditioned hosts with sublethal irradiation plus reduction of NK cells with anti-CD8α mAb treatment, which invariably resulted in acute LT-GvHD. Compared to those in the peripheral counterpart, graft CD4(+) CD25(-) passenger T cells showed lower alloreactivities in mixed leukocyte culture. Immunohistology revealed that donor CD4(+) T cells migrated and formed clusters with host dendritic cells in secondary lymphoid organs, with early expansion and subsequent accumulation in target organs...
October 12, 2016: American Journal of Transplantation
Xinhua Chen, Xueqin Meng, Yuning Xu, Haiyang Xie, Shengyong Yin, Hongchun Li, Liming Wu, Shusen Zheng
BACKGROUND: Graft-versus-host disease (GVHD) after liver and kidney transplantation has high mortality and causes diagnostic challenges. This study aims to describe the cytokine and human leukocyte antigen (HLA) profile in the GVHD after liver and kidney transplantation. METHODS: A high-throughput detection kit was applied and altogether 18 different cytokines were tested simultaneously. GVHD patients included 23 post-liver transplantation patients; 22 post-renal transplantation patients; The control patients include 22 hepatocellular carcinoma (HCC) patients without transplantation and 20 healthy controls...
October 12, 2016: European Journal of Medical Research
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)
Jessica Heinrichs, David Bastian, Anandharaman Veerapathran, Claudio Anasetti, Brain Betts, Xue-Zhong Yu
Graft-versus-host disease (GVHD) is a significant cause of non-relapse mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Existing strategies to prevent and treat GVHD are incomplete, where a significant portion of allo-HCT recipients developed this complication. Despite this, one such therapy has emerged involving the use of regulatory T cells (Tregs) to control GVHD. The use of natural Tregs (nTregs) yielded positive pre-clinical results and are actively under investigation to reduce GVHD...
2016: J Immunol Res Ther
A Nazha, L Rybicki, D Abounader, B Bolwell, R Dean, A T Gerds, D Jagadeesh, B K Hamilton, B T Hill, M Kalaycio, H Liu, B Pohlman, R Sobecks, M A Sekeres, N S Majhail
No abstract text is available yet for this article.
October 10, 2016: Bone Marrow Transplantation
Y Mori, K Ikeda, T Inomata, G Yoshimoto, N Fujii, H Ago, T Teshima
Jak1/2 inhibitor ruxolitinib is a promising agent for treating steroid-refractory GvHD after allogeneic hematopoietic stem cell transplantation (SCT) to produce quick and durable responses. However, optimal dose and tapering schedule of ruxolitinib remain to be determined. Discontinuation of ruxolitinib in myelofibrosis often induces 'withdrawal syndrome' characterized by acute relapse of the disease, but this issue is not well addressed in the treatment of GvHD. Four patients with GvHD (one acute and three chronic) after SCT for myelofibrosis were treated with ruxolitinib...
October 10, 2016: Bone Marrow Transplantation
Geothy Chakupurakal, María Alejandra Garcia-Marquez, Alexander Shimabukuro-Vornhagen, Sandra Kluth, Hans Schlosser, Sebastian Theurich, Christof Scheid, Michael Hallek, Udo Holtick, Michael von Bergwelt-Baildon
OBJECTIVE: The role of B-cells and the subgroup of IL-10 producing B-cells, known to have a regulatory function, in patients following a haematopoetic stem cell transplant (alloSCT) has not been clearly understood to date. METHODS: We prospectively recruited 95 patients following an alloSCT and studied the B-cell reconstitution on days 30, 90 and 150. Regulatory B10-cells could be analysed in 22 consecutively recruited patients on day 30 post transplant. RESULTS: The total B-cell percentages in transplant recipients (median 0...
September 26, 2016: European Journal of Haematology
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