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https://www.readbyqxmd.com/read/28097534/successful-treatment-with-low-dose-nivolumab-in-refractory-hodgkin-lymphoma-after-allogeneic-stem-cell-transplantation
#1
Makoto Onizuka, Minoru Kojima, Keiko Matsui, Shinichiro Machida, Masako Toyosaki, Yasuyuki Aoyama, Hidetsugu Kawai, Jun Amaki, Ryujiro Hara, Akifumi Ichiki, Yoshiaki Ogawa, Hiroshi Kawada, Naoya Nakamura, Kiyoshi Ando
Previous studies have reported that an antibody that blocks programmed cell death 1 (PD-1) has therapeutic activity in patients with refractory/relapsed Hodgkin lymphoma (HL). However, the safety and efficacy of these agents in the post-allogeneic stem cell transplantation (allo-SCT) setting are not well known. Here, we describe a patient who was diagnosed as classical HL and treated with five regimens of chemotherapies with autologous SCT. Complete remission (CR) was not achieved following this initial treatment, so we performed allo-SCT from an HLA-matched sibling donor...
January 17, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28096512/papers-of-note-in-science-translational-medicine-9-372
#2
Leslie K Ferrarelli
This week's papers describe new therapeutic avenues to kill tumor-initiating cells in breast, ovarian, and lung cancer patients; mitigate graft-versus-host disease after hematopoietic cell transplants in leukemia patients; and stimulate bone healing in diabetic patients.
January 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/28096093/lymphangiogenesis-is-a-feature-of-acute-gvhd-and-vegfr-3-inhibition-protects-against-experimental-gvhd
#3
Sarah Mertlitz, Yu Shi, Martina Kalupa, Carsten Grötzinger, Jörg Mengwasser, Katarina Riesner, Steffen Cordes, Sefer Elezkurtaj, Olaf Penack
Lymph vessels play a crucial role for immune reactions in health and disease. In oncology the inhibition of lymphangiogenesis is an established therapeutic concept to reduce metastatic spreading of tumor cells. During allogeneic tissue transplantation the inhibition of lymphangiogenesis has been successfully used to attenuate graft rejection. Despite its critical importance for tumor growth, allo-immune responses and inflammation, the role of lymphangiogenesis has not been investigated during allogeneic hematopoietic stem cell transplantation (allo-HSCT)...
January 17, 2017: Blood
https://www.readbyqxmd.com/read/28096092/initiation-of-acute-graft-versus-host-disease-by-angiogenesis
#4
Katarina Riesner, Yu Shi, Angela Jacobi, Martin Kraeter, Martina Kalupa, Aleixandria McGearey, Sarah Mertlitz, Steffen Cordes, Jens-Florian Schrezenmeier, Jörg Mengwasser, Sabine Westphal, Daniel Perez-Hernandez, Clemens Schmitt, Gunnar Dittmar, Jochen Guck, Olaf Penack
The inhibition of inflammation-associated angiogenesis ameliorates inflammatory diseases by reducing the recruitment of tissue infiltrating leukocytes. However, it is not known if angiogenesis has an active role during the initiation of inflammation or if it is merely a secondary effect occurring in response to stimuli by tissue infiltrating leukocytes. Here we show that angiogenesis precedes leukocyte infiltration in experimental models of inflammatory bowel disease and acute graft-versus-host disease (GVHD)...
January 17, 2017: Blood
https://www.readbyqxmd.com/read/28096088/how-i-treat-acquired-aplastic-anemia
#5
Andrea Bacigalupo
Acquired severe aplastic anemia (SAA) is a rare hematologic disease associated with significant morbidity and mortality. Immune destruction of hemopoietic stem cells, plays an important role in the pathogenesis, as shown by successful treatment with immunosuppressive agents (IST), leading to transfusion independence, or complete recovery of peripheral blood counts, in a proportion of patients. Growth factors, can be combined with IST, and may improve response rates, as recently shown with thrombopoietin analogs...
January 17, 2017: Blood
https://www.readbyqxmd.com/read/28095351/level-of-granzyme-b-positive-t-regulatory-cells-is-a-strong-predictor-biomarker-of-acute-graft-versus-host-disease-after-day-30-after-allo-hsct
#6
Mikhail Y Drokov, Julia O Davydova, Larisa A Kuzmina, Irina V Galtseva, Nikolay M Kapranov, Vera A Vasilyeva, Darya S Dubnyak, Olga M Koroleva, Ekaterina D Mikhalcova, Natalia N Popova, Elena N Parovichnikova, Valery G Savchenko
Acute Graft-versus-host-disease (aGVHD), the major complication and one of the main causes of poor outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nowadays there are no widely accepted cell, plasma or another biomarker that can be used for aGVHD prediction. We hypothesized that a level of Granzyme B-positive T regulatory (GZMB-positive Treg) cells on day+30 after allo-HSCT could be the measure of immune response suppression and could predict aGVHD development after day +30. We applied a widespread and easy-to-perform method of multicolor flow cytometry to measure level of GZMB-positive Treg cells...
January 10, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28094847/increased-regulatory-t-cell-graft-content-is-associated-with-improved-outcome-in-haematopoietic-stem-cell-transplantation-a-systematic-review
#7
Sheila A Fisher, Abigail Lamikanra, Carolyn Dorée, Betty Gration, Pat Tsang, Robert D Danby, David J Roberts
Allogeneic haematopoietic stem cell transplant (HSCT) recipients are at increased risk of morbidity and mortality, often due to the development of acute or chronic graft-versus-host disease (GVHD). Low numbers or proportions of regulatory T cells (Tregs) have been reported in patients who develop GVHD. We undertook a systematic review of studies that reported the Treg composition of HSCT grafts in patients with haematological malignancies. Fourteen eligible studies were identified, eight of which stratified patients by Tregs (absolute dose or ratio to CD3+ or CD4+ cells)...
January 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28091736/salvage-therapy-for-acute-chemorefractory-leukemia-by-allogeneic-stem-cell-transplantation-the-korean-experience
#8
Shin Hye Yoo, Youngil Koh, Dae-Young Kim, Jung-Hee Lee, Je-Hwan Lee, Kyoo-Hyung Lee, Sung-Soo Yoon, Seonyang Park, Sung-Kyu Park, Dae-Sik Hong, Hyeon Gyu Yi, Chul-Soo Kim, Ji Eun Jang, June-Won Cheong, Joonho Moon, Yoo Hong Min, Sang Kyun Sohn, Inho Kim
Little is known about the characteristics that make patients with acute leukemia suitable for undergoing salvage therapy by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we analyzed the clinical outcomes of 223 patients with acute leukemia who underwent allo-HSCT while not in complete remission (CR). The primary end points were overall survival (OS) and CR rate. CR was achieved in 79.8% of patients after allo-HSCT. Acute graft-versus-host disease (GVHD) was significantly associated with CR (P = 0...
January 16, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28089075/conjunctival-impression-cytology-evaluation-of-patients-with-dry-eye-disease-using-scleral-contact-lenses
#9
Sarah La Porta Weber, Rossen Mihaylov Hazarbassanov, Alex Nasaré, José Álvaro Pereira Gomes, Ana Luisa Hofling-Lima
PURPOSE: To evaluate conjunctival impression cytology and HLADR expression changes after wearing scleral contact lenses (ScCLs) for moderate to severe dry eye disease (DED). DESIGN: Prospective interventional case series. METHODS: Forty-one eyes from 25 patients with moderate to severe DED were evaluated for Esclera ScCL treatment. Best-corrected visual acuity (BCVA) and slit-lamp findings were assessed. Impression cytology specimens were obtained from DED patients at the baseline and after wearing ScCLs for 12 months...
January 6, 2017: Contact Lens & Anterior Eye: the Journal of the British Contact Lens Association
https://www.readbyqxmd.com/read/28088653/immune-stimulation-during-chemotherapy-increases-incidence-of-acute-graft-versus-host-disease-in-acute-myeloid-leukemia-a-study-on-behalf-of-sfgm-tc-and-alfa
#10
Lining Wang, Emmanuel Raffoux, Xavier Thomas, Ibrahim Yakoub-Agha, Jean-Henri Bouhris, Stéphane de Botton, Mauricette Michallet, Stéphanie Nguyen Quoc, Xavier Troussard, Eric Deconinck, Denis Caillot, Pascal Turlure, Stéphane Vigouroux, Arnaud Pigneux, Anne Huynh, Jean-Valère Malfuson, Michael Loschi, Gerard Socie, Hervé Dombret, Régis Peffault de la Tour, Thomas Cluzeau
60-70% of AML patients have an indication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) during their treatment. Graft versus host disease (GvHD), the major cause of mortality and comorbidities post-transplantation, develops by immunological mechanism and decides greatly prognosis and quality of life (QoL) of graft recipient. Current GvHD prophylaxis is not personalized. Infections, toxicities and leukemic infiltration complicate the first chemotherapy phases prior to allo-HSCT. They, to certain extent, induce local immune stimulation...
January 5, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28087457/t-cell-replete-peripheral-blood-haploidentical-hematopoietic-cell-transplantation-with-post-transplant-cyclophosphamide-results-in-outcomes-similar-to-traditionally-matched-donors-in-active-disease-acute-myeloid-leukemia
#11
Joan How, Michael Slade, Khoan Vu, John F DiPersio, Peter Westervelt, Geoffrey L Uy, Camille N Abboud, Ravi Vij, Mark A Schroeder, Todd A Fehniger, Rizwan Romee
Outcomes for acute myeloid leukemia (AML) patients who fail to achieve complete remission remain poor. Hematopoietic cell transplantation (HCT) has been shown to induce long-term survival in AML patients with active disease. HCT is largely performed with HLA-matched unrelated or HLA-matched related donors. Recently, HCT with HLA-haploidentical related donors has been identified as a feasible option when HLA-matched donors are not immediately available. However, there is little data comparing outcomes of AML patients with active disease who receive haploidentical versus traditionally matched HCT...
January 10, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28077684/targeting-aurora-kinase-a-and-jak2-prevents-gvhd-while-maintaining-treg-and-antitumor-ctl-function
#12
Brian C Betts, Anandharaman Veerapathran, Joseph Pidala, Hua Yang, Pedro Horna, Kelly Walton, Christopher L Cubitt, Steven Gunawan, Harshani R Lawrence, Nicholas J Lawrence, Said M Sebti, Claudio Anasetti
Graft-versus-host disease (GVHD) is a leading cause of nonrelapse mortality after allogeneic hematopoietic cell transplantation. T cell costimulation by CD28 contributes to GVHD, but prevention is incomplete when targeting CD28, downstream mammalian target of rapamycin (mTOR), or Aurora A. Likewise, interleukin-6 (IL-6)-mediated Janus kinase 2 (JAK2) signaling promotes alloreactivity, yet JAK2 inhibition does not eliminate GVHD. We provide evidence that blocking Aurora A and JAK2 in human T cells is synergistic in vitro, prevents xenogeneic GVHD, and maintains antitumor responses by cytotoxic T lymphocytes (CTLs)...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28073814/donor-derived-mycosis-fungoides-following-reduced-intensity-haematopoietic-stem-cell-transplantation-from-a-matched-unrelated-donor
#13
Francesca A M Kinsella, Mohammad Rasoul Amel Kashipaz, Julia Scarisbrick, Ram Malladi
A 46-year-old woman with a history of dasatinib-resistant chronic myeloid leukaemia, clonal evolution and monosomy 7 underwent reduced intensity conditioned in vivo T-cell-depleted allogeneic haematopoietic stem cell transplantation (HSCT) from a matched unrelated donor. Following the transplantation, she developed recurrent cutaneous graft versus host disease (GvHD), which required treatment with systemic immunosuppression and electrocorporeal photophoresis. Concurrently, she developed a lichenoid rash with granulomatous features suggestive of cutaneous sarcoidosis...
January 10, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28073785/safety-and-efficacy-of-allogeneic-hematopoietic-stem-cell-transplant-after-pd-1-blockade-in-relapsed-refractory-lymphoma
#14
Reid W Merryman, Haesook T Kim, Pier Luigi Zinzani, Carmelo Carlo-Stella, Stephen M Ansell, Miguel-Angel Perales, Abraham Avigdor, Ahmad S Halwani, Roch Houot, Tony Marchand, Nathalie Dhedin, Willy Lescaut, Anne Thiebaut-Bertrand, Sylvie François, Aspasia Stamatoullas-Bastard, Pierre-Simon Rohrlich, Hélène Labussière Wallet, Luca Castagna, Armando Santoro, Veronika Bachanova, Scott C Bresler, Amitabh Srivastava, Harim Kim, Emily Pesek, Marie Chammas, Carol Reynolds, Vincent T Ho, Joseph H Antin, Jerome Ritz, Robert J Soiffer, Philippe Armand
Anti-PD-1 monoclonal antibodies are being increasingly tested in patients with advanced lymphoma. Following treatment, many of those patients are likely to be candidates for allogeneic hematopoietic stem cell transplant (HSCT). However, the safety and efficacy of HSCT may be affected by prior PD-1 blockade. We conducted an international retrospective analysis of 39 patients with lymphoma who received prior treatment with a PD-1 inhibitor, at a median time of 62 days (7-260) before HSCT. After a median follow-up of 12 months, the one-year cumulative incidences of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD) were 44% and 23% respectively, while the one-year incidence of chronic GVHD was 41%...
January 10, 2017: Blood
https://www.readbyqxmd.com/read/28073648/elevated-neutrophil-elastase-in-tears-of-ocular-graft-versus-host-disease-patients
#15
Samer N Arafat, Marie-Claude Robert, Tulio Abud, Sandra Spurr-Michaud, Francisco Amparo, Claes H Dohlman, Reza Dana, Ilene K Gipson
PURPOSE: To investigate the levels of neutrophil elastase (NE), matrix metalloproteinases (MMPs) and myeloperoxidase (MPO) in tear washes of patients with ocular graft-versus-host disease (oGVHD). DESIGN: Case-control study. METHODS: Based on established criteria, oGVHD patients (n = 14; 28 eyes) and age/sex-matched healthy controls (n = 14; 28 eyes) were enrolled. Tear washes were collected and analyzed for NE using a single-analyte enzyme-linked immunosorbent assay (ELISA)...
January 7, 2017: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/28068510/current-knowledge-and-priorities-for-future-research-in-late-effects-after-hematopoietic-stem-cell-transplantation-hct-for-severe-combined-immunodeficiency-patients-a-consensus-statement-from-the-second-pediatric-blood-and-marrow-transplant-consortium-international
#16
REVIEW
Jennifer Heimall, Jennifer Puck, Rebecca Buckley, Thomas A Fleisher, Andrew R Gennery, Benedicte Neven, Mary Slatter, Elie Haddad, Luigi D Notarangelo, K Scott Baker, Andrew C Dietz, Christine Duncan, Michael A Pulsipher, Mort J Cowan
Severe combined immunodeficiency (SCID) is 1 of the most common indications for pediatric hematopoietic cell transplantation (HCT) in patients with primary immunodeficiency. Historically, SCID was diagnosed in infants who presented with opportunistic infections within the first year of life. With newborn screening (NBS) for SCID in most of the United States, the majority of infants with SCID are now diagnosed and treated in the first 3.5 months of life; however, in the rest of the world, the lack of NBS means that most infants with SCID still present with infections...
January 6, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28067900/donor-cd19-car-t-cells-exert-potent-graft-versus-lymphoma-activity-with-diminished-graft-versus-host-activity
#17
Arnab Ghosh, Melody Smith, Scott E James, Marco L Davila, Enrico Velardi, Kimon V Argyropoulos, Gertrude Gunset, Fabiana Perna, Fabiana M Kreines, Emily R Levy, Sophie Lieberman, Hillary V Jay, Andrea Z Tuckett, Johannes L Zakrzewski, Lisa Tan, Lauren F Young, Kate Takvorian, Jarrod A Dudakov, Robert R Jenq, Alan M Hanash, Ana Carolina F Motta, George F Murphy, Chen Liu, Andrea Schietinger, Michel Sadelain, Marcel R M van den Brink
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies. However, graft-versus-host disease (GVHD) and relapse after allo-HSCT remain major impediments to the success of allo-HSCT. Chimeric antigen receptors (CARs) direct tumor cell recognition of adoptively transferred T cells. CD19 is an attractive CAR target, which is expressed in most B cell malignancies, as well as in healthy B cells. Clinical trials using autologous CD19-targeted T cells have shown remarkable promise in various B cell malignancies...
January 9, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28067684/diarrhea-after-allogeneic-stem-cell-transplantation-beyond-graft-versus-host-disease
#18
Katarzyna Robak, Joanna Zambonelli, Jaroslaw Bilinski, Grzegorz W Basak
Diarrhea constitutes a frequent and often debilitating complication of allogeneic hematopoietic cell transplantation (alloHCT). Especially when accompanied by jaundice, skin rash, and symptoms of the upper gastrointestinal tract, diarrhea strongly suggests emergence of acute graft-versus-host disease (GvHD), which is a serious immune complication of the procedure, with possible fatal consequences. However, especially when diarrhea occurs as an isolated symptom, the other causes must be excluded before initiation of GvHD treatment with immune-suppressive drugs...
January 6, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28067665/selective-graft-versus-leukemia-depends-on-magnitude-and-diversity-of-the-alloreactive-t-cell-response
#19
Cornelis A M van Bergen, Simone A P van Luxemburg-Heijs, Liesbeth C de Wreede, Matthijs Eefting, Peter A von dem Borne, Peter van Balen, Mirjam H M Heemskerk, Arend Mulder, Fransiscus H J Claas, Marcelo A Navarrete, Wilhelmina M Honders, Caroline E Rutten, Hendrik Veelken, Inge Jedema, Constantijn J M Halkes, Marieke Griffioen, J H Frederik Falkenburg
Patients with leukemia who receive a T cell-depleted allogeneic stem cell graft followed by postponed donor lymphocyte infusion (DLI) can experience graft-versus-leukemia (GVL) reactivity, with a lower risk of graft-versus-host disease (GVHD). Here, we have investigated the magnitude, diversity, and specificity of alloreactive CD8 T cells in patients who developed GVL reactivity after DLI in the absence or presence of GVHD. We observed a lower magnitude and diversity of CD8 T cells for minor histocompatibility antigens (MiHAs) in patients with selective GVL reactivity without GVHD...
January 9, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28065838/current-results-and-future-research-priorities-in-late-effects-after-hematopoietic-stem-cell-transplantation-hct-for-children-with-sickle-cell-disease-and-thalassemia-a-consensus-statement-from-the-second-pediatric-blood-and-marrow-transplant-consortium-international
#20
Shalini Shenoy, Emanuele Angelucci, Staci D Arnold, K Scott Baker, Monica Bhatia, Dorine Bresters, Andrew C Dietz, Josu De La Fuente, Christine Duncan, Javid Gaziev, Allison A King, Michael A Pulsipher, Angela Smith, Mark C Walters
Sustained donor engraftment after allogeneic hematopoietic cell transplantation (HCT) converts to healthy donor hemoglobin synthesis and halts disease symptoms in patients with sickle cell disease (SCD) and thalassemia major. A disease free survival probability that exceeds 90% has been reported when HCT using an HLA-matched sibling donor is performed in young patients with low risk disease or treatment related risk factors. Alternate donor HCT and HCT in adults is performed infrequently due to a higher risk profile...
January 5, 2017: Biology of Blood and Marrow Transplantation
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