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https://www.readbyqxmd.com/read/27890260/the-role-of-second-transplants-for-leukemia
#1
REVIEW
Daniel Weisdorf
Management of relapsed leukemia following allogeneic transplantation is challenging. Intensive chemotherapy, donor lymphocyte infusions (DLI), or second transplantation have some value, but most reported series describe only a limited number of patients surviving beyond 2 or 3 years following relapse. Additionally, understandable selection-bias of reports describing the outcomes of intensive management approaches for relapsed leukemia confound generalizability to a broader population. However numerous reports suggest that second allogeneic transplantation for relapsed leukemia following an initial transplant may produce extended disease control and survival for patients with favorable performance status, remission at the time of second transplant, and most importantly a long interval between initial transplant and relapse...
December 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27890259/how-important-is-nk-alloreactivity-and-kir-in-allogeneic-transplantation
#2
REVIEW
Brian C Shaffer, Katharine C Hsu
Relapse of acute myelogenous leukemia (AML) after allogeneic hematopoietic cell transplantation (allo HCT) is a major cause of death in transplant recipients. Efforts to control relapse by promoting donor T-cell alloreactivity, such as withdrawal of immune suppression or donor lymphocyte infusions, are limited by the propensity to induce graft versus host disease (GVHD) and by inadequate efficacy. Therefore, options for AML patients who have relapsed AML after allo HCT are few and outcomes are poor. Similar to T-cells, natural killer (NK) cells have potent anti-leukemia effector capacity, and yet unlike T-cells, NK cells do not mediate GVHD...
December 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27881982/milestones-of-hematopoietic-stem-cell-transplantation-from-first-human-studies-to-current-developments
#3
REVIEW
Mateja Kralj Juric, Sakhila Ghimire, Justyna Ogonek, Eva M Weissinger, Ernst Holler, Jon J van Rood, Machteld Oudshoorn, Anne Dickinson, Hildegard T Greinix
Since the early beginnings, in the 1950s, hematopoietic stem cell transplantation (HSCT) has become an established curative treatment for an increasing number of patients with life-threatening hematological, oncological, hereditary, and immunological diseases. This has become possible due to worldwide efforts of preclinical and clinical research focusing on issues of transplant immunology, reduction of transplant-associated morbidity, and mortality and efficient malignant disease eradication. The latter has been accomplished by potent graft-versus-leukemia (GvL) effector cells contained in the stem cell graft...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27802969/ibrutinib-efficacy-and-tolerability-in-patients-with-relapsed-chronic-lymphocytic-leukemia-following-allogeneic-hct
#4
Christine E Ryan, Bita Sahaf, Aaron C Logan, Susan O'Brien, John C Byrd, Peter Hillmen, Jennifer R Brown, Martin J S Dyer, Anthony R Mato, Michael J Keating, Samantha Jaglowski, Fong Clow, Andrew R Rezvani, Lori Styles, Steven E Coutre, David B Miklos
Ibrutinib, a potent and irreversible small molecule inhibitor of both Bruton's tyrosine kinase (BTK) and interleukin-2 inducible kinase (ITK), has been used to treat relapsed/refractory chronic lymphocytic leukemia (CLL) with prolongation of progression-free and overall survival. Here we present 27 patients with relapsed CLL following allogeneic hematopoietic cell transplantation who subsequently received ibrutinib salvage therapy. Sixteen of these patients were part of multi-institutional clinical trials and achieved an overall response rate of 87...
November 1, 2016: Blood
https://www.readbyqxmd.com/read/27788764/haploidentical-cord-transplantation-the-best-of-both-worlds
#5
REVIEW
Koen van Besien, Richard Childs
Haploidentical (haplo)-cord transplantation combines infusion of an umbilical cord blood (UCB) unit with CD34-selected cells usually from human leukocyte antigen (HLA) mismatched donors. Initial rapid count recovery from the haplo-hematopoietic progenitors, is gradually replaced by durable engraftment from UCB progenitors. UCB grafts used for haplo-cord are smaller, but better matched than those required for single or double UCB stem cell transplant (SCT). More than 200 patients with hematological malignancies have been transplanted...
October 2016: Seminars in Hematology
https://www.readbyqxmd.com/read/27788763/haploidentical-transplants-using-ex-vivo-t-cell-depletion
#6
REVIEW
Massimo F Martelli, Franco Aversa
Allogeneic hematopoietic stem cell transplantation (HSCT) is the best post-remission therapy for patients with acute leukemia (AL) at high risk of relapse. Advantages of having a family member as donor include: no undue delay in obtaining the graft; choice of best donor with regards to natural killer (NK) alloreactivity and cytomegalovirus (CMV) status from a panel of candidate family members; easy access to post-transplant cellular therapies like donor lymphocyte infusions and opportunity for a second graft from the original donor, or another family member in case of graft failure...
October 2016: Seminars in Hematology
https://www.readbyqxmd.com/read/27784742/allogeneic-stem-cell-transplantation-a-historical-and-scientific-overview
#7
REVIEW
Anurag K Singh, Joseph P McGuirk
The field of hematopoietic stem cell transplant (HSCT) has made ground-breaking progress in the treatment of many malignant and nonmalignant conditions. It has also pioneered the concepts of stem cell therapy and immunotherapy as a tool against cancer. The success of transplant for hematologic malignancies derives both from the ability to treat patients with intensive chemoradiotherapy and from potent graft-versus-leukemia (GVL) effects mediated by donor immunity. Additionally, HSCT has been a curative therapy for several nonmalignant hematologic disorders through the provision of donor-derived hematopoiesis and immunity...
October 26, 2016: Cancer Research
https://www.readbyqxmd.com/read/27777140/unrelated-cord-blood-transplantation-for-acute-leukemia-diagnosed-in-the-first-year-of-life-outcomes-and-risk-factor-analysis
#8
Annalisa Ruggeri, Fernanda Volt, Franco Locatelli, Gerard Michel, Cristina Diaz de Heredia, Manuel Abecasis, Marco Zecca, Ajay Vora, Karima Yakouben, Tracey A O'Brien, Stefano Giardino, Jacqueline Cornish, Vanderson Rocha, Christina Peters, Peter Bader, Eliane Gluckman, Jean Hugues Dalle
Infant acute leukemia still has a poor prognosis, and allogeneic hematopoietic stem cell transplantation is indicated in selected patients. Umbilical cord blood (UCB) is an attractive cell source for this population because of the low risk of chronic graft-versus-host disease (GVHD), the strong graft-versus-leukemia effect, and prompt donor availability. This retrospective, registry-based study reported UCB transplantation (UCBT) outcomes in 252 children with acute lymphoblastic leukemia (ALL; n = 157) or acute myelogenous leukemia (AML; n = 95) diagnosed before 1 year of age who received a single-unit UCBT after myeloablative conditioning between 1996 and 2012 in European Group for Blood and Marrow Transplantation centers...
October 21, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27746218/recipient-hla-c-haplotypes-and-microrna-148a-b-binding-sites-have-no-impact-on-allogeneic-hematopoietic-cell-transplantation-outcomes
#9
Gretchen A Hoff, Johannes C Fischer, Katharine Hsu, Sarah Cooley, Jeffrey S Miller, Tao Wang, Michael Haagenson, Stephen Spellman, Stephanie J Lee, Markus Uhrberg, Jeffrey M Venstrom, Michael R Verneris
Natural killer cells are important in graft-versus-leukemia responses after hematopoietic cell transplantation (HCT). A variety of surface receptors dictates natural killer cell function, including killer cell immunoglobulin-like receptor recognition of HLA-C. Previous single-center studies show that HLA-C epitopes, designated C1 and C2, were associated with allogeneic HCT outcomes; specifically, recipients homozygous for the C1 epitope (C1/C1) experienced a survival benefit. Additionally, mismatching at HLA-C was beneficial in recipients possessing at least 1 C2 allele, whereas the opposite was true for homozygous C1 (C1/C1) recipients where HLA-C mismatching resulted in worse outcomes...
October 13, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27727179/t-cell-receptor-excision-circle-trec-monitoring-after-allogeneic-stem-cell-transplantation-a-predictive-marker-for-complications-and-clinical-outcome
#10
Ahmed Gaballa, Mikael Sundin, Arwen Stikvoort, Muhamed Abumaree, Mehmet Uzunel, Darius Sairafi, Michael Uhlin
Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established treatment modality for a variety of malignant diseases as well as for inborn errors of the metabolism or immune system. Regardless of disease origin, good clinical effects are dependent on proper immune reconstitution. T cells are responsible for both the beneficial graft-versus-leukemia (GVL) effect against malignant cells and protection against infections. The immune recovery of T cells relies initially on peripheral expansion of mature cells from the graft and later on the differentiation and maturation from donor-derived hematopoietic stem cells...
October 11, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27722210/regulatory-t-cell-therapy-for-graft-versus-host-disease
#11
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: Journal of Immunology Research and Therapy
https://www.readbyqxmd.com/read/27707998/g-csf-induced-suppressor-il-10-neutrophils-promote-regulatory-t-cells-that-inhibit-graft-versus-host-disease-in-a-long-lasting-and-specific-way
#12
Suelen Martins Perobelli, Ana Carolina Terra Mercadante, Rômulo Gonçalves Galvani, Triciana Gonçalves-Silva, Ana Paula Gregório Alves, Antonio Pereira-Neves, Marlene Benchimol, Alberto Nóbrega, Adriana Bonomo
Acute graft-versus-host disease (aGVHD) is the main complication of allogeneic hematopoietic stem cell transplantation, and many efforts have been made to overcome this important limitation. We showed previously that G-CSF treatment generates low-density splenic granulocytes that inhibit experimental aGVHD. In this article, we show that aGVHD protection relies on incoming IL-10(+) neutrophils from G-CSF-treated donor spleen (G-Neutrophils). These G-Neutrophils have high phagocytic capacity, high peroxide production, low myeloperoxidase activity, and low cytoplasmic granule content, which accounts for their low density...
October 5, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27671676/modulation-of-immune-checkpoints-and-graft-versus-leukemia-in-allogeneic-transplants-by-antagonizing-vasoactive-intestinal-peptide-signaling
#13
Jian-Ming Li, Christopher T Petersen, Jing-Xia Li, Reema Panjwani, Daniel J Chandra, Cynthia R Giver, Bruce R Blazar, Edmund K Waller
The goal of allogeneic bone marrow transplantation (allo-BMT) is elimination of leukemia cells through the graft-versus-leukemia (GvL) activity of donor cells, while limiting graft-versus-host disease (GvHD). Immune checkpoint pathways regulate GvL and GvHD activities, but blocking antibodies or genetic inactivation of these pathways can cause lethal GVHD. Vasoactive intestinal peptide (VIP) is an immunosuppressive neuropeptide that regulates coinhibitory pathways; its role in allo-BMT has not been studied...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27634018/induction-of-immune-response-after-allogeneic-wilms-tumor-1-dendritic-cell-vaccination-and-donor-lymphocyte-infusion-in-patients-with-hematologic-malignancies-and-post-transplantation-relapse
#14
Nirali N Shah, David M Loeb, Hahn Khuu, David Stroncek, Tolu Ariyo, Mark Raffeld, Cindy Delbrook, Crystal L Mackall, Alan S Wayne, Terry J Fry
Relapse of hematologic malignancies is the primary cause of treatment failure after allogeneic hematopoietic stem cell transplantation (HCT). Treatment for post-HCT relapse using donor lymphocyte infusion (DLI) has limited utility, particularly in the setting of acute leukemia, and can result in the development of graft-versus-host disease (GVHD). The Wilms' tumor 1 (WT1) gene product is a tumor-associated antigen that is expressed in acute leukemia and other hematologic malignancies, with limited expression in normal tissues...
September 12, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27618144/ponatinib-induces-a-persistent-molecular-response-and-graft-versus-host-disease-graft-versus-leukemia-effect-in-a-patient-with-philadelphia-positive-acute-lymphoblastic-leukemia-with-a-t315i-mutation-following-early-relapse-after-allogeneic-transplant
#15
Daniela Renzi, Francesco Marchesi, Gottardo De Angelis, Loredana Elia, Emanuela Salvatorelli, Svitlana Gumenyuk, Francesca Palombi, Francesco Pisani, Atelda Romano, Antonio Spadea, Elena Papa, Marco Canfora, William Arcese, Andrea Mengarelli
We describe the case of a patient with a Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with dasatinib plus steroids as the first-line therapy who achieved a molecular complete remission and then underwent a matched, unrelated donor allogeneic transplant. Five months after the transplant, he experienced a disease relapse with an T315I mutation, which was resistant to salvage chemotherapy. Once the details of the T315I mutation were acquired, we initiated ponatinib treatment at a standard dosage and observed a rapid decrease of minimal residual disease (MRD) at molecular assessment...
September 10, 2016: Chemotherapy
https://www.readbyqxmd.com/read/27549307/matching-for-the-nonconventional-mhc-i-mica-gene-significantly-reduces-the-incidence-of-acute-and-chronic-gvhd
#16
Raphael Carapito, Nicolas Jung, Marius Kwemou, Meiggie Untrau, Sandra Michel, Angélique Pichot, Gaëlle Giacometti, Cécile Macquin, Wassila Ilias, Aurore Morlon, Irina Kotova, Petya Apostolova, Annette Schmitt-Graeff, Anne Cesbron, Katia Gagne, Machteld Oudshoorn, Bronno van der Holt, Myriam Labalette, Eric Spierings, Christophe Picard, Pascale Loiseau, Ryad Tamouza, Antoine Toubert, Anne Parissiadis, Valérie Dubois, Xavier Lafarge, Myriam Maumy-Bertrand, Frédéric Bertrand, Luca Vago, Fabio Ciceri, Catherine Paillard, Sergi Querol, Jorge Sierra, Katharina Fleischhauer, Arnon Nagler, Myriam Labopin, Hidetoshi Inoko, Peter A von dem Borne, Jürgen Kuball, Masao Ota, Yoshihiko Katsuyama, Mauricette Michallet, Bruno Lioure, Régis Peffault de Latour, Didier Blaise, Jan J Cornelissen, Ibrahim Yakoub-Agha, Frans Claas, Philippe Moreau, Noël Milpied, Dominique Charron, Mohamad Mohty, Robert Zeiser, Gérard Socié, Seiamak Bahram
Graft-versus-host disease (GVHD) is among the most challenging complications in unrelated donor hematopoietic cell transplantation (HCT). The highly polymorphic MHC class I chain-related gene A, MICA, encodes a stress-induced glycoprotein expressed primarily on epithelia. MICA interacts with the invariant activating receptor NKG2D, expressed by cytotoxic lymphocytes, and is located in the MHC, next to HLA-B Hence, MICA has the requisite attributes of a bona fide transplantation antigen. Using high-resolution sequence-based genotyping of MICA, we retrospectively analyzed the clinical effect of MICA mismatches in a multicenter cohort of 922 unrelated donor HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 10/10 allele-matched HCT pairs...
October 13, 2016: Blood
https://www.readbyqxmd.com/read/27531680/cd4-t-cell-alloreactivity-towards-mismatched-hla-class-ii-alleles-early-after-double-umbilical-cord-blood-transplantation-ducbt
#17
Cor H J Lamers, Rebecca Wijers, Cornelis A M van Bergen, Judith A E Somers, Eric Braakman, Jan Willem Gratama, Reno Debets, J H Frederik Falkenburg, Jan J Cornelissen
While double umbilical cord blood transplantation (dUCBT) in adult patients may be associated with less graft failure as compared to single UCBT, hematopoietic recovery generally originates from a single cord blood unit (CBU). CBU predominance is still incompletely understood. We recently showed that blood CD4+ T-cell numbers rapidly increase after dUCBT and early CD4+ T-cell chimerism predicts for graft predominance. Given the frequent HLA-class II allele mismatches between CBUs in dUCBT, we hypothesized that alloreactive HLA-class II-specific CD4+ T-cells from the 'winning' CBU may contribute to rejection of the 'loser' CBU...
August 16, 2016: Blood
https://www.readbyqxmd.com/read/27525074/blinatumomab-may-induce-graft-versus-host-leukemia-in-patients-with-pre-b-all-relapsing-after-hematopoietic-stem-cell-transplant
#18
Muhammad Waqas Khan, Zartash Gul
Blinatumomab, a bispecific T-cell engager monoclonal antibody used to manage Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) can be used to treat patients by inducing graft versus leukemia reaction post allogeneic hematopoietic stem cell transplantation, a feature which it was post allogeneic bone marrow transplantation, a feature which this drug was not aimed to do.
August 2016: Clinical Case Reports
https://www.readbyqxmd.com/read/27473564/longitudinal-analyses-of-leukemia-associated-antigen-specific-cd8-t%C3%A2-cells-in-patients-after-allogeneic-stem-cell-transplantation
#19
Elke Rücker-Braun, Cornelia S Link, Maria Schmiedgen, Antje Tunger, Petra Vizjak, Raphael Teipel, Rebekka Wehner, Denise Kühn, Yannik F Fuchs, Uta Oelschlägel, Lothar Germeroth, Marc Schmitz, Martin Bornhäuser, Johannes Schetelig, Falk Heidenreich
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment approach for patients with acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). Graft versus leukemia (GVL) effects, which are exerted by donor T cells directed against leukemic-associated antigens (LAAs), are considered to play a crucial role in disease eradication. Although the expansion of cytotoxic T lymphocytes (CTLs) specific for cytomegalovirus (CMV) in response to an infection has been shown in multiple studies, data on CTLs mediating GVL effects are limited...
November 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27471614/cd8-tregs-promote-gvhd-prevention-and-overcome-the-impaired-gvl-effect-mediated-by-cd4-tregs-in-mice
#20
Jessica Heinrichs, Jun Li, Hung Nguyen, Yongxia Wu, David Bastian, Anusara Daethanasanmak, M-Hanief Sofi, Steven Schutt, Chen Liu, Junfei Jin, Brian Betts, Claudio Anasetti, Xue-Zhong Yu
Adoptive natural regulatory T cell (nTreg) therapy has improved the outcome for patients suffering from graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (Allo-HCT). However, fear of broad immune suppression and subsequent dampening of beneficial graft-versus-leukemia (GVL) responses remains a challenge. To address this concern, we generated alloreactive induced Tregs (iTregs) from resting CD4(+) or CD8(+) T cells and tested their ability to suppress GVH and maintain GVL responses...
June 2016: Oncoimmunology
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