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Transplantation induction therapies

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https://www.readbyqxmd.com/read/29330757/-myelodysplastic-syndrome-acute-leukemia-and-stem-cell-transplantation
#1
REVIEW
M Schmalzing, M Aringer, M Bornhäuser, J Atta
Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem cell disorders. They are characterized by inefficient hematopoiesis leading to peripheral cytopenia of one or more lineages and a variable risk of transformation into acute myeloid leukemia. They may either arise de novo as well as following exposition to environmental toxins, previous radiotherapy or chemotherapy or in the context of autoinflammatory diseases and related therapy. Characteristic cytogenetic abnormalities, along with the numbers of hematopoietic lineages affected and bone marrow blasts, enable an assessment of the risk of leukemic transformation...
October 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/29330746/risk-stratified-therapy-for-children-with-flt3-itd-positive-acute-myeloid-leukemia-results-from-the-jplsg-aml-05-study
#2
Akira Shimada, Yuka Iijima-Yamashita, Akio Tawa, Daisuke Tomizawa, Miho Yamada, Shiba Norio, Tomoyuki Watanabe, Takashi Taga, Shotaro Iwamoto, Kiminori Terui, Hiroshi Moritake, Akitoshi Kinoshita, Hiroyuki Takahashi, Hideki Nakayama, Katsuyoshi Koh, Hiroaki Goto, Yoshiyuki Kosaka, Akiko Moriya Saito, Nobutaka Kiyokawa, Keizo Horibe, Yusuke Hara, Kentaro Oki, Yasuhide Hayashi, Shiro Tanaka, Souichi Adachi
Acute myeloid leukemia harboring internal tandem duplication of FMS-like tyrosine kinase 3 (AMLFLT3-ITD) is associated with poor prognosis. We evaluated the results of the AML-05 study, in which all AMLFLT3-ITD patients were assigned to receive hematopoietic stem cell transplantation (HSCT) in the first remission (1CR). We also investigated the effects of additional genetic alterations on FLT3-ITD. The 5-year overall survival (OS) and event-free survival (EFS) rates among the 47 AMLFLT3-ITD patients were 42...
January 12, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29330112/macrochimerism-and-clinical-transplant-tolerance
#3
REVIEW
John D Scandling, Stephan Busque, Robert Lowsky, Judith Shizuru, Asha Shori, Edgar Engleman, Kent Jensen, Samuel Strober
Current theory holds that macrochimerism is essential to the development of transplant tolerance. Hematopoietic cell transplantation from the solid organ donor is necessary to achieve macrochimerism. Over the last 10 to 20 years, trials of tolerance induction with combined kidney and hematopoietic cell transplantation have moved from the preclinical to the clinical arena. The achievement of macrochimerism in the clinical setting is challenging, and potentially toxic due to the conditioning regimen necessary to hematopoietic cell transplantation and due to the risk of graft-versus-host disease...
January 9, 2018: Human Immunology
https://www.readbyqxmd.com/read/29326196/young-adults-perspectives-on-living-with-kidney-failure-a-systematic-review-and-thematic-synthesis-of-qualitative-studies
#4
Phillippa K Bailey, Alexander J Hamilton, Rhian L Clissold, Carol D Inward, Fergus J Caskey, Yoav Ben-Shlomo, Amanda Owen-Smith
INTRODUCTION: Young adults fare worse than younger adolescents or older adults on a broad range of health indicators. Those with a chronic illness such as renal failure are a particularly vulnerable group, who experience poor outcomes compared with both children and older adults. Understanding how being in receipt of renal replacement therapy (RRT) affects the lives of young adults might help us to better prepare and support these individuals for and on RRT, and improve outcomes. This study aimed to synthesise research describing young adults' experiences of the psychosocial impact of kidney failure and RRT...
January 10, 2018: BMJ Open
https://www.readbyqxmd.com/read/29325898/treatment-of-mantle-cell-lymphoma-in-older-adults
#5
REVIEW
Daniel F Pease, Vicki A Morrison
Mantle cell lymphoma (MCL) predominantly affects older adults, with a median age at diagnosis of 70years. A frequently aggressive yet incurable lymphoma, the goal of therapy for MCL is to turn a potentially life-threatening illness into a chronic disease with prolonged periods of remission. Large randomized trial data supports the standard treatment in younger patients of cytarabine-based induction followed by autologous stem cell transplant. Most patients will not be eligible for this intensive approach based on older age, comorbidities, and functional status, making the geriatric assessment an essential step in choosing the appropriate strategy...
January 8, 2018: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/29321554/mutations-in-dnmt3a-u2af1-and-ezh2-identify-intermediate-risk-acute-myeloid-leukemia-patients-with-poor-outcome-after-cr1
#6
Caner Saygin, Cassandra Hirsch, Bartlomiej Przychodzen, Mikkael A Sekeres, Betty K Hamilton, Matt Kalaycio, Hetty E Carraway, Aaron T Gerds, Sudipto Mukherjee, Aziz Nazha, Ronald Sobecks, Christopher Goebel, Donna Abounader, Jaroslaw P Maciejewski, Anjali S Advani
Intermediate-risk acute myeloid leukemia (IR-AML) is a clinically heterogeneous disease, for which optimal post-remission therapy is debated. The utility of next-generation sequencing information in decision making for IR-AML has yet to be elucidated. We retrospectively studied 100 IR-AML patients, defined by European Leukemia Net classification, who had mutational information at diagnosis, received intensive chemotherapy and achieved complete remission (CR) at Cleveland Clinic (CC). The Cancer Genome Atlas (TCGA) data were used for validation...
January 10, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29312561/therapeutic-effects-of-adipose-derived-mesenchymal-stem-cells-against-brain-death-induced-remote-organ-damage-and-post-heart-transplant-acute-rejection
#7
Hon-Kan Yip, Mel S Lee, Cheuk-Kwan Sun, Kuan-Hung Chen, Han-Tan Chai, Pei-Hsun Sung, Kun-Chen Lin, Sheung-Fat Ko, Chun-Man Yuen, Chu-Feng Liu, Pei-Lin Shao, Fan-Yen Lee
We tested the hypothesis that allogenic adipose-derived mesenchymal stem cells (ADMSCs) alleviated brain death (BD)-induced remote organ damage and events of post heart-transplant acute rejection. To determine the impact of BD on remote organ damage, adult-male F344 rats (n=24) were categorized sham-control (SC), BD and BDMSC (allogenic ADMSC/1.2 × 106 cells/derived from F344 by intravenous transfusion 3 h after BD procedure). To determine the protective effect of allogenic ADMSCs, animals (n=8/each group in F344/Lewis) were categorized into groups BD-T(F344 heart transplanted into Lewis by 6h after BD), BD-TMSC(D1/3) (BD induction for 6h then heart transplantation, and allogenic ADMSCs transfusion at days 1 and 5 after heart transplantation), BD-TMSC(3h) (BD + ADMSC/1...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29304833/a-phase-i-study-of-selinexor-in-combination-with-high-dose-cytarabine-and-mitoxantrone-for-remission-induction-in-patients-with-acute-myeloid-leukemia
#8
Amy Y Wang, Howard Weiner, Margaret Green, Hua Chang, Noreen Fulton, Richard A Larson, Olatoyosi Odenike, Andrew S Artz, Michael R Bishop, Lucy A Godley, Michael J Thirman, Satyajit Kosuri, Jane E Churpek, Emily Curran, Kristen Pettit, Wendy Stock, Hongtao Liu
BACKGROUND: Novel therapies for patients with acute myeloid leukemia (AML) are imperative, particularly for those with high-risk features. Selinexor, an exportin 1 (XPO1/CRM1) inhibitor, has demonstrated anti-leukemia activity as a single agent, as well as in combination with anthracyclines and/or DNA-damaging agents. METHODS: We report the findings of a phase I dose escalation trial with cohort expansion in 20 patients with newly diagnosed or relapsed/refractory AML that combined selinexor with age-adjusted high-dose cytarabine and mitoxantrone (HiDAC/Mito)...
January 5, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29304724/treatment-patterns-healthcare-resource-utilization-and-costs-in-patients-with-acute-myeloid-leukemia-in-commercially-insured-and-medicare-populations
#9
Eytan M Stein, Gaetano Bonifacio, Dominick Latremouille-Viau, Annie Guerin, Sherry Shi, Patrick Gagnon-Sanschagrin, Owanate Briggs, George J Joseph
OBJECTIVE: To describe the setting, duration, and costs of induction and consolidation chemotherapy for adults with newly diagnosed acute myeloid leukemia (AML), who are candidates for standard induction chemotherapy, in the United States. METHODS: Adults newly diagnosed with AML who received standard induction chemotherapy in an inpatient setting were identified from the Truven Health Analytics MarketScan (2006-2015) and SEER-Medicare (2007-2011) databases. Patients were observed from induction therapy start to the first of hematopoietic stem cell transplant, 180 days after induction discharge, health plan enrollment/data availability end, or death...
January 5, 2018: Journal of Medical Economics
https://www.readbyqxmd.com/read/29303612/the-effect-of-induction-therapy-on-established-cmv-specific-t-cell-immunity-in-living-donor-kidney-transplantation
#10
L Stranavova, P Hruba, E Girmanova, I Tycova, A Slavcev, J Fronek, J Slatinska, P Reinke, H-D Volk, O Viklicky
Cytomegalovirus (CMV) infection influences both short and long term outcomes in immunosuppressed organ transplant recipients. The aim of this study was to evaluate the effect of different induction immunosuppression regimens on CMV specific T cell response in patients with already established CMV immunity. In 24 seropositive living donor kidney recipients, the frequency of CMV specific T cells was determined by ELISPOT (Enzyme-Linked ImmunoSpot) assay prior and 6 months after transplantation. Recipients' peripheral blood mononuclear cells were stimulated with immediate-early (IE1) and phosphoprotein 65 (pp65) CMV-derived peptide pools and the number of cells producing interferon gamma (IFN-gamma) was assessed...
January 5, 2018: Physiological Research
https://www.readbyqxmd.com/read/29303357/the-synergy-of-two-factors-on-insulin-expression
#11
Ying Luo, Yao Xu, Zhen-Yu Wang, Xi Li, Wei-Bing Xing, Tong-Cun Zhang
As a potential cure for diabetes, more and more attentions have been paid to organ transplants to replace insulin therapy. As a result, many researchers have explored out many programs to get insulin-producing cells (IPCs) to replace the defective β cells. Currently, more and more new induction methods are being proposed, and at the same time, more and more possible induction molecular mechanisms are being revealed. The purpose of this study was to explore whether and how the two factors pdx-1 and myocardin affected the differentiation of rat mesenchymal stem cells (rMSCs) into IPCs...
January 5, 2018: Cellular Reprogramming
https://www.readbyqxmd.com/read/29302684/autologous-transplantation-for-newly-diagnosed-multiple-myeloma-in-the-era-of-novel-agent-induction-a-systematic-review-and-meta-analysis
#12
Binod Dhakal, Aniko Szabo, Saurabh Chhabra, Mehdi Hamadani, Anita D'Souza, Saad Z Usmani, Rita Sieracki, Bishal Gyawali, Jeffrey L Jackson, Fotis Asimakopoulos, Parameswaran N Hari
Importance: The role of high-dose therapy with melphalan followed by autologous stem cell transplant (HDT/ASCT) in patients with multiple myeloma continues to be debated in the context of novel agent induction. Objective: To perform a systematic review, conventional meta-analysis, and network meta-analysis of all phase 3 randomized clinical trials (RCTs) evaluating the role of HDT/ASCT. Data Sources: We performed a systematic literature search of Cochrane Central, MEDLINE, and Scopus from January 2000 through April 2017 and relevant annual meeting abstracts from January 2014 to December 2016...
January 4, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29302022/effect-of-immunosuppression-on-target-blood-immune-cells-within-1-year-after-lung-transplantation-influence-of-age-on-t-lymphocytes
#13
Benjamin Coiffard, Matthieu Pelardy, Anderson D Loundou, Corine Nicolino-Brunet, Pascal Alexandre Thomas, Laurent Papazian, Françoise Dignat-George, Martine Reynaud-Gaubert
BACKGROUND Lymphocytes are targeted by immunosuppressive therapy in solid organ transplantation and they influence allograft outcome. MATERIAL AND METHODS Peripheral blood lymphocyte subsets (PBLS) determined by flow cytometry during the first year post-transplant from patients who underwent a first lung transplantation in a French University Hospital between December 2011 and July 2013 were retrospectively analyzed according to recipient characteristics and allograft outcome. RESULTS Fifty-seven recipients were enrolled and 890 PBLS were collected...
January 5, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/29296864/immune-tolerance-induction-by-nonmyeloablative-haploidentical-hsct-combining-t-cell-depletion-and-posttransplant-cyclophosphamide
#14
Franco Aversa, Esther Bachar-Lustig, Noga Or-Geva, Lucia Prezioso, Sabrina Bonomini, Ilenia Manfra, Alessandro Monti, Chiara Schifano, Yael Zlotnikov-Klionsky, Massimo F Martelli, Gabriella Sammarelli, Maria Sassi, Maurizio Soli, Silvia Giuliodori, Magda Benecchi, Nicola Giuliani, Frank Lohr, Silvia Pratissoli, Yair Reisner
The establishment of safe approaches to attain durable donor-type chimerism and immune tolerance toward donor antigens represents a major challenge in transplantation biology. Haploidentical hematopoietic stem cell transplantation (HSCT) is currently used for cancer therapy either as a T-cell-depleted megadose HSCT following myeloablative conditioning or with T-cell-replete HSCT following nonmyeloablative conditioning (NMAC) and high-dose posttransplant cyclophosphamide (PTCY). The latter approach suffers from a significant rate of chronic graft-versus-host disease (GVHD), despite prolonged immunosuppression...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288697/mesenchymal-stromal-cells-for-tolerance-induction-in-organ-transplantation
#15
REVIEW
Federica Casiraghi, Norberto Perico, Giuseppe Remuzzi
The primary challenge in organ transplantation continues to be the need to suppress the host immune system long-term to ensure prolonged allograft survival. Long-term non-specific immunosuppression can, however, result in life-threatening complications. Thus, efforts have been pursued to explore novel strategies that would allow minimization of maintenance immunosuppression, eventually leading to transplant tolerance. In this scenario, bone marrow-derived mesenchymal stromal cells (MSC), given their given unique immunomodulatory properties to skew the balance between regulatory and memory T cells, have emerged as potential candidates for cell-based therapy to promote immune tolerance...
December 27, 2017: Human Immunology
https://www.readbyqxmd.com/read/29288671/prolonged-skin-grafts-survival-time-by-ifn-%C3%AE-in-allogeneic-skin-transplantation-model-during-acute-rejection-through-ifn-%C3%AE-stat3-ido-pathway-in-epidermal-layer
#16
Yijie Zhang, Yunchuan Wang, Gaofeng Wu, Wei Zhang, Xujie Wang, Weixia Cai, Julei Zhang, Shichao Han, Yan Li, Xiaozhi Bai, Jihong Shi, Linlin Su, Dahai Hu
Allogeneic skin transplantation is the life-saving therapy for multiple diseases, including extensive burn, large-scale trauma and certain post-surgical complications. However, acute rejection impedes clinical application of allogeneic skin transplantation. Although a lot of novel immunosuppressant drugs have been developed, there is still great need for ideal therapy with less complication and more therapeutic effects. Here, we found interferon gamma (IFN-γ) as an immunomodulatory cytokine prolonged the survival time of allografts from (8...
December 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29282899/analysis-of-long-term-survival-in-multiple-myeloma-after-first-line-autologous-stem-cell-transplantation-impact-of-clinical-risk-factors-and-sustained-response
#17
Nicola Lehners, Natalia Becker, Axel Benner, Maria Pritsch, Martin Löpprich, Elias Karl Mai, Jens Hillengass, Hartmut Goldschmidt, Marc-Steffen Raab
The widespread use of high-dose therapy and autologous stem cell transplantation (ASCT) as well as the introduction of novel agents have significantly improved outcomes in multiple myeloma (MM) enabling long-term survival. We here analyze factors influencing survival in 865 newly diagnosed MM patients who underwent first-line ASCT at our center between 1993 and 2014. Relative survival and conditional survival were assessed to further characterize long-term survivors. Achievement of complete response (CR) post-ASCT was associated with prolonged progression-free survival (PFS) in the whole cohort and with significantly superior overall survival (OS) in the subgroup of patients receiving novel agent-based induction therapy...
December 28, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29279741/generation-of-induced-pluripotent-stem-cells-and-neural-stem-progenitor-cells-from-newborns-with-spina-bifida-aperta
#18
Yohei Bamba, Masahiro Nonaka, Natsu Sasaki, Tomoko Shofuda, Daisuke Kanematsu, Hiroshi Suemizu, Yuichiro Higuchi, Ritsuko K Pooh, Yonehiro Kanemura, Hideyuki Okano, Mami Yamasaki
Study Design: We established induced pluripotent stem cells (iPSCs) and neural stem/progenitor cells (NSPCs) from three newborns with spina bifida aperta (SBa) using clinically practical methods. Purpose: We aimed to develop stem cell lines derived from newborns with SBa for future therapeutic use. Overview of Literature: SBa is a common congenital spinal cord abnormality that causes defects in neurological and urological functions. Stem cell transplantation therapies are predicted to provide beneficial effects for patients with SBa...
December 2017: Asian Spine Journal
https://www.readbyqxmd.com/read/29259971/alk1fc-suppresses-the-human-prostate-cancer-growth-in-in-vitro-and-in-vivo-preclinical-models
#19
Letizia Astrologo, Eugenio Zoni, Sofia Karkampouna, Peter C Gray, Irena Klima, Joël Grosjean, Marie J Goumans, Lukas J A C Hawinkels, Gabri van der Pluijm, Martin Spahn, George N Thalmann, Peter Ten Dijke, Marianna Kruithof-de Julio
Prostate cancer is the second most common cancer in men and lethality is normally associated with the consequences of metastasis rather than the primary tumor. Therefore, targeting the molecular pathways that underlie dissemination of primary tumor cells and the formation of metastases has a great clinical value. Bone morphogenetic proteins (BMPs) play a critical role in tumor progression and this study focuses on the role of BMP9- Activin receptor-Like Kinase 1 and 2 (ALK1 and ALK2) axis in prostate cancer...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29259578/t-cell-mediated-beta-cell-destruction-autoimmunity-and-alloimmunity-in-the-context-of-type-1-diabetes
#20
REVIEW
Adam L Burrack, Tijana Martinov, Brian T Fife
Type 1 diabetes (T1D) results from destruction of pancreatic beta cells by T cells of the immune system. Despite improvements in insulin analogs and continuous blood glucose level monitoring, there is no cure for T1D, and some individuals develop life-threatening complications. Pancreas and islet transplantation have been attractive therapeutic approaches; however, transplants containing insulin-producing cells are vulnerable to both recurrent autoimmunity and conventional allograft rejection. Current immune suppression treatments subdue the immune system, but not without complications...
2017: Frontiers in Endocrinology
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