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Leo luznik

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https://www.readbyqxmd.com/read/28254742/pirfenidone-ameliorates-murine-chronic-gvhd-through-inhibition-of-macrophage-infiltration-and-tgf-%C3%AE-production
#1
Jing Du, Katelyn Paz, Ryan Flynn, Ante Vulic, Tara M Robinson, Katie E Lineburg, Kylie A Alexander, Jingjing Meng, Sabita Roy, Angela Panoskaltsis-Mortari, Michael Loschi, Geoffrey R Hill, Jonathan S Serody, Ivan Maillard, David Miklos, John Koreth, Corey S Cutler, Joseph H Antin, Jerome Ritz, Kelli P MacDonald, Timothy W Schacker, Leo Luznik, Bruce R Blazar
Allogeneic hematopoietic stem cell transplantation is hampered by chronic graft-versus-host disease (cGVHD) resulting in multi-organ fibrosis and diminished function. Fibrosis in lung and skin leads to progressive bronchiolitis obliterans (BO) and scleroderma, respectively, for which new treatments are needed. We evaluated pirfenidone, a FDA approved drug for idiopathic pulmonary fibrosis, for its therapeutic effect in cGVHD mouse models with distinct pathophysiology. In a full MHC-mismatched, multi-organ system model with BO, donor T cell responses that support pathogenic antibody production are required for cGVHD development...
March 2, 2017: Blood
https://www.readbyqxmd.com/read/28126963/plasma-derived-proteomic-biomarkers-in-hla-haploidentical-or-hla-matched-bone-marrow-transplantation-using-post-transplantation-cyclophosphamide
#2
Christopher G Kanakry, Giorgos Bakoyannis, Susan M Perkins, Shannon R McCurdy, Ante Vulic, Edus H Warren, Etienne Daguindau, Taylor Olmsted, Christen Mumaw, Andrea M H Towlerton, Kenneth R Cooke, Paul V O'Donnell, Heather J Symons, Sophie Paczesny, Leo Luznik
Recent studies have suggested that plasma-derived proteins may be potential biomarkers relevant for graft-versus-host disease and/or non-relapse mortality occurring after allogeneic blood or marrow transplantation. However, none of these putative biomarkers have been assessed in patients treated either with HLA-haploidentical blood or marrow transplantation or with post-transplantation cyclophosphamide, which has been repeatedly associated with low rates of severe acute graft-versus-host disease, chronic graft-versus-host disease, and non-relapse mortality...
January 25, 2017: Haematologica
https://www.readbyqxmd.com/read/28062216/post-transplantation-cyclophosphamide-after-bone-marrow-transplantation-is-not-associated-with-an-increased-risk-of-donor-derived-malignancy
#3
Robbie G Majzner, Huzefa Mogri, Ravi Varadhan, Patrick Brown, Kenneth R Cooke, Javier Bolaños-Meade, Lode Swinnen, Jennifer Kanakry, Leo Luznik, Richard J Jones, Ephraim Fuchs, Rich Ambinder, Yvette Kasamon, Heather J Symons
Post-transplantation cyclophosphamide (PTCy) can be used for graft-versus-host disease (GVHD) prophylaxis alone or in combination with other agents and is associated with excellent rates of engraftment and acute and chronic GVHD, as well as absence of post-transplantation lymphoproliferative disease. No study has previously evaluated the risk for developing donor-derived malignancy (DDM) in patients who receive PTCy. Giving chemotherapy in the immediate post-transplantation period carries with it a theoretic risk of disturbing the graft at a time of increased hematopoietic stress and causing or accelerating the development of malignancy...
January 3, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28049637/low-immunosuppressive-burden-after-hla-matched-related-or-unrelated-bmt-using-posttransplantation-cyclophosphamide
#4
Christopher G Kanakry, Javier Bolaños-Meade, Yvette L Kasamon, Marianna Zahurak, Nadira Durakovic, Terry Furlong, Marco Mielcarek, Marta Medeot, Ivana Gojo, B Douglas Smith, Jennifer A Kanakry, Ivan M Borrello, Robert A Brodsky, Douglas E Gladstone, Carol Ann Huff, William H Matsui, Lode J Swinnen, Kenneth R Cooke, Richard F Ambinder, Ephraim J Fuchs, Marcos J de Lima, Borje S Andersson, Ravi Varadhan, Paul V O'Donnell, Richard J Jones, Leo Luznik
The intensive and prolonged immunosuppressive therapy required to prevent or treat graft-versus-host disease (GVHD) after allogeneic blood or marrow transplantation (alloBMT) puts patients at substantial risk for life-threatening infections, organ toxicity, and disease relapse. Posttransplantation cyclophosphamide (PTCy) can function as single-agent GVHD prophylaxis after myeloablative, HLA-matched related (MRD), or HLA-matched unrelated (MUD) donor T-cell-replete bone marrow allografting, obviating the need for additional prophylactic immunosuppression...
March 9, 2017: Blood
https://www.readbyqxmd.com/read/27888014/nonmyeloablative-haploidentical-bone-marrow-transplantation-with-post-transplantation-cyclophosphamide-for-pediatric-and-young-adult-patients-with-high-risk-hematologic-malignancies
#5
Orly R Klein, Jessica Buddenbaum, Noah Tucker, Allen R Chen, Christopher J Gamper, David Loeb, Elias Zambidis, Nicolas J Llosa, Jeffrey S Huo, Nancy Robey, Mary Jo Holuba, Yvette L Kasamon, Shannon R McCurdy, Richard Ambinder, Javier Bolaños-Meade, Leo Luznik, Ephraim J Fuchs, Richard J Jones, Kenneth R Cooke, Heather J Symons
Lower-intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious for adult patients with hematologic malignancies. We report data for pediatric/young adult patients with high-risk hematologic malignancies (n = 40) treated with nonmyeloablative haploidentical BMT with post-transplantation cyclophosphamide from 2003 to 2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplantation immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus...
February 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27861294/induction-of-major-histocompatibility-complex-mismatched-mouse-lung-allograft-acceptance-with-combined-donor-bone-marrow-lung-transplant-using-a-12-hour-nonmyeloablative-conditioning-regimen
#6
Jeffrey M Dodd-O, Sudipto Ganguly, Ante Vulic, Angela Panoskaltsis-Mortari, John F McDyer, Leo Luznik
BACKGROUND: Despite broad and intense conventional immunosuppression, long-term survival after lung transplantation lags behind that for other solid organ transplants, primarily because of allograft rejection. Therefore, new strategies to promote lung allograft acceptance are urgently needed. The purpose of the present study was to induce allograft tolerance with a protocol compatible with deceased donor organ utilization. METHODS: Using the major histocompatibility complex-mismatched mouse orthotopic lung transplant model, we investigated a conditioning regimen consisting of pretransplant T cell depletion, low-dose total body irradiation and posttransplant (donor) bone marrow, and splenocyte infusion followed by posttransplantation cyclophosphamide...
December 2016: Transplantation
https://www.readbyqxmd.com/read/27846611/comparable-composite-endpoints-after-hla-matched-and-hla-haploidentical-transplantation-with-post-transplantation-cyclophosphamide
#7
Shannon R McCurdy, Yvette L Kasamon, Christopher G Kanakry, Javier Bolaños-Meade, Hua-Ling Tsai, Margaret M Showel, Jennifer A Kanakry, Heather J Symons, Ivana Gojo, B Douglas Smith, Maria P Bettinotti, William H Matsui, Amy E Dezern, Carol Ann Huff, Ivan Borrello, Keith W Pratz, Douglas E Gladstone, Lode J Swinnen, Robert A Brodsky, Mark J Levis, Richard F Ambinder, Ephraim J Fuchs, Gary L Rosner, Richard J Jones, Leo Luznik
Composite endpoints that not only encompass mortality and relapse, but other critical post-transplant events such as graft-versus-host disease, are being increasingly utilized to quantify survival without significant morbidity after allogeneic blood or marrow transplantation. High-dose, post-transplantation cyclophosphamide reduces severe graft-versus-host disease with allogeneic marrow transplantation, making composite endpoints after this management particularly interesting. We retrospectively analyzed 684 adults with hematologic malignancies who received T-cell-replete bone marrow grafts and cyclophosphamide after myeloablative HLA-matched related (n=192) or unrelated (n=120), or non-myeloablative HLA-haploidentical (n=372) donor transplantation...
February 2017: Haematologica
https://www.readbyqxmd.com/read/27713092/the-biology-of-chronic-graft-versus-host-disease-a-task-force-report-from-the-national-institutes-of-health-consensus-development-project-on-criteria-for-clinical-trials-in-chronic-graft-versus-host-disease
#8
REVIEW
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, nonrelapse mortality and disability in allogeneic hematopoietic cell transplantation recipients and a major obstacle to improving outcomes. The biology of chronic GVHD 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: This document is intended as a review of our understanding of chronic GVHD biology and therapies resulting from preclinical studies, and as a platform for developing innovative clinical strategies to prevent and treat chronic GVHD...
February 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27638363/for-whom-the-bell-tolls-programmed-death-1-as-a-marker-of-post-transplantation-mortality
#9
Tara M Robinson, Leo Luznik
No abstract text is available yet for this article.
September 13, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27385791/therapeutic-regulatory-t-cell-adoptive-transfer-ameliorates-established-murine-chronic-gvhd-in-a-cxcr5-dependent-manner
#10
Cameron McDonald-Hyman, Ryan Flynn, Angela Panoskaltsis-Mortari, Nicholas Peterson, Kelli P A MacDonald, Geoffrey R Hill, Leo Luznik, Jonathan S Serody, William J Murphy, Ivan Maillard, David H Munn, Laurence A Turka, John Koreth, Corey S Cutler, Robert J Soiffer, Joseph H Antin, Jerome Ritz, Bruce R Blazar
Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation. In cGVHD, alloreactive T cells and germinal center (GC) B cells often participate in GC reactions to produce pathogenic antibodies. Although regulatory T cells (Tregs) can inhibit GC reactions, Treg numbers are reduced in cGVHD, contributing to cGVHD pathogenesis. Here, we explored 2 means to increase Tregs in cGVHD: interleukin-2/monoclonal antibody (IL-2/mAb) complexes and donor Treg infusions...
August 18, 2016: Blood
https://www.readbyqxmd.com/read/27213183/origin-and-evolution-of-the-t-cell-repertoire-after-posttransplantation-cyclophosphamide
#11
Christopher G Kanakry, David G Coffey, Andrea M H Towlerton, Ante Vulic, Barry E Storer, Jeffrey Chou, Cecilia C S Yeung, Christopher D Gocke, Harlan S Robins, Paul V O'Donnell, Leo Luznik, Edus H Warren
Posttransplantation cyclophosphamide (PTCy) effectively prevents graft-versus-host disease (GVHD), but its immunologic impact is poorly understood. We assessed lymphocyte reconstitution via flow cytometry (n = 74) and antigen receptor sequencing (n = 35) in recipients of myeloablative, HLA-matched allogeneic BM transplantation using PTCy. Recovering T cells were primarily phenotypically effector memory with lower T cell receptor β (TRB) repertoire diversity than input donor repertoires. Recovering B cells were predominantly naive with immunoglobulin heavy chain locus (IGH) repertoire diversity similar to donors...
2016: JCI Insight
https://www.readbyqxmd.com/read/27071449/how-do-we-choose-the-best-donor-for-t-cell-replete-hla-haploidentical-transplantation
#12
REVIEW
Ying-Jun Chang, Leo Luznik, Ephraim J Fuchs, Xiao-Jun Huang
In haploidentical stem cell transplantations (haplo-SCT), nearly all patients have more than one donor. A key issue in the haplo-SCT setting is the search for the best donor, because donor selection can significantly impact the incidences of acute and chronic graft-versus-host disease, transplant-related mortality, and relapse, in addition to overall survival. In this review, we focused on factors associated with transplant outcomes following unmanipulated haplo-SCT with anti-thymocyte globulin (ATG) or after T-cell-replete haplo-SCT with post-transplantation cyclophosphamide (PT/Cy)...
April 12, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27000732/haploidentical-bone-marrow-and-stem-cell-transplantation-experience-with-post-transplantation-cyclophosphamide
#13
REVIEW
Tara M Robinson, Paul V O'Donnell, Ephraim J Fuchs, Leo Luznik
Allogeneic blood or bone marrow transplantation (BMT) is a potentially curative therapy for high-risk hematologic malignancies not curable by standard chemotherapy, but the procedure is limited by the availability of human leukocyte antigen-matched donors for many patients, as well as toxicities including graft-versus-host disease (GVHD). Our group has developed the use of high-dose post-transplantation cyclophosphamide (PTCy) to selectively remove alloreactive T cells without compromising engraftment. This protocol has allowed for successful transplantation of human leukocyte antigen (HLA)-haploidentical (haplo) grafts, thus expanding the donor pool for the many patients who would not otherwise be a candidate for this life-saving procedure...
April 2016: Seminars in Hematology
https://www.readbyqxmd.com/read/26983850/targeted-rho-associated-kinase-2-inhibition-suppresses-murine-and-human-chronic-gvhd-through-a-stat3-dependent-mechanism
#14
Ryan Flynn, Katelyn Paz, Jing Du, Dawn K Reichenbach, Patricia A Taylor, Angela Panoskaltsis-Mortari, Ante Vulic, Leo Luznik, Kelli K P MacDonald, Geoffrey R Hill, Melanie S Nyuydzefe, Jonathan M Weiss, Wei Chen, Alissa Trzeciak, Jon S Serody, Ethan G Aguilar, William J Murphy, Ivan Maillard, David Munn, John Koreth, Corey S Cutler, Joseph H Antin, Jerome Ritz, Samuel D Waksal, Alexandra Zanin-Zhorov, Bruce R Blazar
Chronic graft-versus-host disease (cGVHD) remains a major complication following allogeneic bone marrow transplantation (BMT). The discovery of novel therapeutics is dependent on assessment in preclinical murine models of cGVHD. Rho-associated kinase 2 (ROCK2) recently was shown to be implicated in regulation of interleukin-21 (IL-21) and IL-17 secretion in mice and humans. Here, we report that the selective ROCK2 inhibitor KD025 effectively ameliorates cGVHD in multiple models: a full major histocompatibility complex (MHC) mismatch model of multiorgan system cGVHD with bronchiolitis obliterans syndrome and a minor MHC mismatch model of sclerodermatous GVHD...
April 28, 2016: Blood
https://www.readbyqxmd.com/read/26893397/might-haplo-be-the-better-match
#15
COMMENT
Jennifer A Kanakry, Leo Luznik
No abstract text is available yet for this article.
February 18, 2016: Blood
https://www.readbyqxmd.com/read/26806585/proceedings-from-the-second-haploidentical-stem-cell-transplantation-symposium-haplo2014-san-francisco-california-december-4-2014
#16
Monzr M Al Malki, Mary Horowitz, Rupert Handgretinger, Wing Leung, Denis-Claude Roy, Xiao-Jun Huang, Ephraim Fuchs, Franco Locatelli, Didier Blaise, Shin Mineishi, Massimo Martelli, Jeffrey Miller, Carl June, Hui-Sheng Ai, Leo Luznik, Domenico Mavilio, Enrico Lugli, Marcel R M van den Brink, Richard E Champlin, Stefan O Ciurea
Significant progress has been made over the past decade in haploidentical transplantation, with the development of novel methods to control intense alloreactive reactions generated in the major HLA-mismatched setting. Application of post-transplantation cyclophosphamide has gained worldwide acceptance as an effective and low-cost way to perform this type of transplantation, with outcomes now similar to those from HLA-matched unrelated donors. These advances have resulted in improved treatment-related mortality, whereas disease relapse has emerged as the most common cause of treatment failure...
April 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/26576864/anti-cd45-radioimmunotherapy-without-tbi-before-transplantation-facilitates-persistent-haploidentical-donor-engraftment
#17
Johnnie J Orozco, Aimee Kenoyer, Ethan R Balkin, Ted A Gooley, Donald K Hamlin, D Scott Wilbur, Mark D Hylarides, Sofia H L Frost, Raya Mawad, Paul O'Donnell, Brenda M Sandmaier, Ephraim J Fuchs, Leo Luznik, Damian J Green, Ajay K Gopal, Oliver W Press, John M Pagel
Many patients with hematologic malignancies cannot tolerate hematopoietic cell transplantation (HCT), whereas others may not have a compatible human leukocyte antigen-matched donor. To overcome these limitations, we optimized a conditioning regimen employing anti-CD45 radioimmunotherapy (RIT) replacing total body irradiation (TBI) before haploidentical HCT in a murine model. Mice received 200 to 400 μCi (90)Y-anti-CD45 antibody (30F11), with or without fludarabine (5 days starting day -8), with cyclophosphamide (CY; days -2 and +2) for graft-versus-host disease prophylaxis, and 1...
January 21, 2016: Blood
https://www.readbyqxmd.com/read/26343947/single-agent-post-transplantation-cyclophosphamide-as-graft-versus-host-disease-prophylaxis-after-human-leukocyte-antigen-matched-related-bone-marrow-transplantation-for-pediatric-and-young-adult-patients-with-hematologic-malignancies
#18
Elad Jacoby, Allen Chen, David M Loeb, Christopher J Gamper, Elias Zambidis, Nicolas J Llosa, Jeffrey Huo, Kenneth R Cooke, Rick Jones, Ephraim Fuchs, Leo Luznik, Heather J Symons
High-dose cyclophosphamide given after HLA-matched related and unrelated allogeneic bone marrow transplantation (BMT) for patients with hematologic malignancies is effective single-agent graft-versus-host disease (GVHD) prophylaxis in adults. Data describing outcomes for pediatric and young adult patients have not been reported. Between the years 2007 and 2013, 29 pediatric and young adult patients ages ≤21 years of age treated at our institution for high-risk hematologic malignancies underwent myeloablative HLA-matched related T cell-replete BMT...
January 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/26305035/modern-approaches-to-hla-haploidentical-blood-or-marrow-transplantation
#19
REVIEW
Christopher G Kanakry, Ephraim J Fuchs, Leo Luznik
Allogeneic blood or bone-marrow transplantation (alloBMT) is a potentially curative treatment for a variety of haematological malignancies and nonmalignant diseases. Historically, human leukocyte antigen (HLA)-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with alloBMT using other donors. Although only approximately one-third of patients have an HLA-matched sibling, nearly all patients have HLA-haploidentical related donors. Early studies using HLA-haploidentical alloBMT resulted in unacceptably high rates of graft rejection and graft-versus-host disease (GVHD), leading to high nonrelapse mortality and consequently poor survival...
January 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/26292764/therapeutic-drug-monitoring-for-either-oral-or-intravenous-busulfan-when-combined-with-pre-and-post-transplantation-cyclophosphamide
#20
Lindsey R Lombardi, Christopher G Kanakry, Marianna Zahurak, Nadira Durakovic, Javier Bolaños-Meade, Yvette L Kasamon, Douglas E Gladstone, William Matsui, Ivan Borrello, Carol Ann Huff, Lode J Swinnen, Robert A Brodsky, Richard F Ambinder, Ephraim J Fuchs, Gary L Rosner, Richard J Jones, Leo Luznik
Busulfan (Bu)/cyclophosphamide (Cy) is a standard conditioning platform for allogeneic transplantation. We developed a strategy separating the Cy into two pre/post-transplantation doses (PTCy), providing myeloablative conditioning and single-agent graft-versus-host disease (GVHD) prophylaxis. We investigated the impact of Bu route on treatment-related toxicity for 131 consecutive adult patients. Busulfan was administered in four daily divided doses either orally (n = 72) or intravenously (n = 59) with pharmacokinetics on the first-dose and as necessary on subsequent doses to achieve a target area-under-the-concentration-curve (AUC) of 800-1400 μmol*min/L per dose...
2016: Leukemia & Lymphoma
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