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Leo luznik

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https://www.readbyqxmd.com/read/27888014/nonmyeloablative-haploidentical-bone-marrow-transplantation-with-post-transplant-cyclophosphamide-for-pediatric-and-young-adult-patients-with-high-risk-hematologic-malignancies
#1
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 (PT/Cy) from 2003-2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplant immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus...
November 22, 2016: 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
#2
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-posttransplantation-cyclophosphamide
#3
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 posttransplant 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, posttransplantation cyclophosphamide reduces severe graft-versus-host disease after allogeneic marrow transplantation, making its composite endpoints of particular interest. We retrospectively analyzed 684 adults with hematologic malignancies who received T-cell-replete bone marrows and posttransplantation cyclophosphamide after myeloablative HLA-matched related (n= 192) or unrelated (n=120), or nonmyeloablative HLA-haploidentical (n = 372) donor transplantation; median follow up was 4 (range 0...
October 20, 2016: 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
#4
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...
October 3, 2016: 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
#5
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
#6
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
#7
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
#8
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)...
2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27000732/haploidentical-bone-marrow-and-stem-cell-transplantation-experience-with-post-transplantation-cyclophosphamide
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
https://www.readbyqxmd.com/read/26261255/outcomes-of-nonmyeloablative-hla-haploidentical-blood-or-marrow-transplantation-with-high-dose-post-transplantation-cyclophosphamide-in-older-adults
#17
Yvette L Kasamon, Javier Bolaños-Meade, Gabrielle T Prince, Hua-Ling Tsai, Shannon R McCurdy, Jennifer A Kanakry, Gary L Rosner, Robert A Brodsky, Karlo Perica, B Douglas Smith, Douglas E Gladstone, Lode J Swinnen, Margaret M Showel, William H Matsui, Carol Ann Huff, Ivan Borrello, Keith W Pratz, Michael A McDevitt, Ivana Gojo, Amy E Dezern, Satish Shanbhag, Mark J Levis, Leo Luznik, Richard F Ambinder, Ephraim J Fuchs, Richard J Jones
PURPOSE: Recent advances in nonmyeloablative (NMA), related HLA-haploidentical blood or marrow transplantation (haplo-BMT) have expanded the donor pool. This study evaluated the effect of age on NMA haplo-BMT outcomes in patients age 50 to 75 years. PATIENTS AND METHODS: A retrospective analysis was performed of 271 consecutive patients with hematologic malignancies, age 50 to 75 years, who received NMA, T-cell-replete haplo-BMT with high-dose post-transplantation cyclophosphamide...
October 1, 2015: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/26183076/phase-ii-study-of-nonmyeloablative-allogeneic-bone-marrow-transplantation-for-b-cell-lymphoma-with-post-transplantation-rituximab-and-donor-selection-based-first-on-non-hla-factors
#18
Jennifer A Kanakry, Christopher D Gocke, Javier Bolaños-Meade, Douglas E Gladstone, Lode J Swinnen, Amanda L Blackford, Ephraim J Fuchs, Carol Ann Huff, Ivan Borrello, William H Matsui, Robert A Brodsky, Gary L Rosner, Satish Shanbhag, Leo Luznik, Richard J Jones, Richard F Ambinder, Yvette L Kasamon
Outcomes of nonmyeloablative (NMA), HLA-haploidentical (haplo), related-donor allogeneic blood or marrow transplantation (allo-BMT) with high-dose post-transplantation cyclophosphamide (PTCy) appear to be similar to those using HLA-matched donors. Thus, it may be possible to prioritize donor factors other than HLA matching that could enhance antitumor activity. The Fc receptor polymorphism FCGR3A-158VV may confer greater sensitivity to rituximab than FCGR3A-158FF. In a prospective phase II study of NMA, related-donor allo-BMT with PTCy and post-transplantation rituximab for patients with B cell lymphomas, we hypothesized that donor selection that prioritized FCGR3A-158 polymorphism over HLA matching would be feasible, safe, and improve outcomes...
December 2015: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/26130705/haploidentical-transplant-with-posttransplant-cyclophosphamide-vs-matched-unrelated-donor-transplant-for-acute-myeloid-leukemia
#19
Stefan O Ciurea, Mei-Jie Zhang, Andrea A Bacigalupo, Asad Bashey, Frederick R Appelbaum, Omar S Aljitawi, Philippe Armand, Joseph H Antin, Junfang Chen, Steven M Devine, Daniel H Fowler, Leo Luznik, Ryotaro Nakamura, Paul V O'Donnell, Miguel-Angel Perales, Sai Ravi Pingali, David L Porter, Marcie R Riches, Olle T H Ringdén, Vanderson Rocha, Ravi Vij, Daniel J Weisdorf, Richard E Champlin, Mary M Horowitz, Ephraim J Fuchs, Mary Eapen
We studied adults with acute myeloid leukemia (AML) after haploidentical (n = 192) and 8/8 HLA-matched unrelated donor (n = 1982) transplantation. Haploidentical recipients received calcineurin inhibitor (CNI), mycophenolate, and posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis; 104 patients received myeloablative and 88 received reduced intensity conditioning regimens. Matched unrelated donor transplant recipients received CNI with mycophenolate or methotrexate for GVHD prophylaxis; 1245 patients received myeloablative and 737 received reduced intensity conditioning regimens...
August 20, 2015: Blood
https://www.readbyqxmd.com/read/26111471/alternative-donor-allogeneic-hematopoietic-cell-transplantation-for-acute-myeloid-leukemia
#20
REVIEW
Christopher G Kanakry, Marcos J de Lima, Leo Luznik
Allogeneic hematopoietic cell transplantation (alloHCT) provides a potentially curative therapy for patients with high-risk or chemorefractory acute myeloid leukemia (AML). Historically, the applicability of alloHCT has been limited as only 30%-35% of patients have human leukocyte antigen (HLA)-matched siblings and outcomes using other donor types have been markedly inferior due to excess toxicity, graft failure, graft-versus-host disease (GVHD), and consequently non-relapse mortality. Advances in HLA typing, GVHD prophylactic approaches, and other transplantation techniques have successfully addressed these historical challenges...
July 2015: Seminars in Hematology
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