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Graft-versus-leukemia

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https://www.readbyqxmd.com/read/28067665/selective-graft-versus-leukemia-depends-on-magnitude-and-diversity-of-the-alloreactive-t-cell-response
#1
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/28058217/review-of-allogeneic-hematopoietic-stem-cell-transplantation-with-reduced-intensity-conditioning-in-solid-tumors-excluding-breast-cancer
#2
REVIEW
Nuri Karadurmus, Ugur Sahin, Bilgin Bahadir Basgoz, Fikret Arpaci, Taner Demirer
Solid tumors in adults constitute a heterogeneous group of malignancy originating from various organ systems. Solid tumors are not completely curable by chemotherapy, even though some subgroups are very chemo-sensitive. Recently, oncologists have focused on the use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced intensity conditioning (RIC) for the treatment of some refractory solid tumors. After the demonstration of allogeneic graft-versus-leukemia effect in patients with hematological malignancies who received allo-HSCT, investigators evaluated this effect in patients with refractory metastatic solid tumors...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28027963/donor-lymphocyte-infusions-in-aml-and-mds-enhancing-the-graft-versus-leukemia-effect
#3
REVIEW
G Orti, P Barba, L Fox, O Salamero, F Bosch, D Valcarcel
No abstract text is available yet for this article.
December 24, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/28008806/role-of-il-26-cd26-cd4-t-cells-in-pulmonary-chronic-graft-versus-host-disease-and-treatment-with-caveolin-1-ig-fc-conjugate
#4
Kei Ohnuma, Ryo Hatano, Takumi Itoh, Noriaki Iwao, Nam H Dang, Chikao Morimoto
Obliterative bronchiolitis is the primary noninfectious pulmonary complication after allogeneic hematopoietic cell transplantation and the only pathognomonic manifestation of pulmonary chronic graft-versus-host disease (cGVHD). In our recent study, we identified a novel effect of IL-26, which is absent in rodents, on transplant related-obliterative bronchiolitis. Sublethally irradiated NOD/Shi-scidIL2rγnull mice transplanted with human umbilical cord blood gradually exhibited obliterative bronchiolitis with increased collagen deposition and predominant infiltration with human IL-26+CD26+CD4 T cells...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27982314/immunotherapy-with-natural-killer-cells-a-possible-approach-for-the-treatment-of-acute-myeloid-leukemia-also-in-brazil
#5
Lúcia Silla
The allogeneic hematopoietic stem cell transplantation (HSCT) can cure intermediate and high-risk acute myeloid leukemia. Even with the development of strategies to reduce HSCT toxicity, this is still a complex treatment with high morbidity and mortality. Knowledge of the graft versus leukemia effect of HSCT has prepared the way for the development of Adoptive Immunotherapy or in vitro expansion of activated lymphocytes without alloreactivity, with subsequent intravenous infusion. The infusion of genetically modified T lymphocytes and haploidentical natural killer cells has been tested as an alternative to HSCT with very interesting results worldwide and in Brazil, as we not only have the technology of in vitro expansion of clinical grade lymphocytes available, but also do it according to the Good Manufacturing Practices that have been determined internationally...
October 2016: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/27932143/report-from-the-first-and-second-spanish-killer-immunoglobulin-like-receptor-genotyping-workshops-external-quality-control-for-natural-killer-alloreactive-donor-selection-in-haploidentical-stem-cell-transplantation
#6
D Planelles, C Vilches, F González-Escribano, M Muro, R González-Fernández, F Sánchez, J Gonzalo Ocejo, A Eiras, J L Caro, E Palou, J A Campillo, M D de Juan, O Montes, A Balas, L Marín, A Torío, M Fernández-Arquero, C González-Roiz, A López-Vázquez, E Cisneros, C Abad-Molina, R López, M L Abad-Alastruey, C Serra, A M García-Alonso, J L Vicario
An important factor affecting the success in the setting of related haploidentical hematopoietic stem cell transplantation (HSCT) is the graft-versus-leukemia effect mediated by natural killer (NK) cells when the donor displays NK alloreactivity versus the recipient. NK cell function is regulated by killer immunoglobulin-like receptors (KIR) and it has been described that donor KIR genotype influences transplantation outcome. This has led to a requirement of laboratories to have a quality assurance program for validation and control of their KIR genotyping methods...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27927772/anti-thymocyte-globulin-as-graft-versus-host-disease-prevention-in-the-setting-of-allogeneic-peripheral-blood-stem-cell-transplantation-a-review-from-the-acute-leukemia-working-party-of-the-european-society-for-blood-and-marrow-transplantation
#7
Frédéric Baron, Mohamad Mohty, Didier Blaise, Gérard Socié, Myriam Labopin, Jordi Esteve, Fabio Ciceri, Sebastian Giebel, Norbert Claude Gorin, Bipin N Savani, Christoph Schmid, Arnon Nagler
Allogeneic hematopoietic stem cell transplantation is increasingly used as treatment for patients with life threatening blood diseases. Their curative potential is largely based on immune-mediated graft-versus-leukemia effects caused by donor T cells contained in the graft. Unfortunately, donor T cells are also the cause of graft-versus-host disease. The vast majority of HLA-matched allogeneic hematopoietic stem cell transplantations are nowadays carried out with peripheral blood stem cells (PBSC) as stem cell source...
December 7, 2016: Haematologica
https://www.readbyqxmd.com/read/27927647/gvhd-prevents-nk-cell-dependent-leukemia-and-virus-specific-innate-immunity
#8
Mark D Bunting, Antiopi Varelias, Fernando Souza-Fonseca-Guimaraes, Iona S Schuster, Katie E Lineburg, Rachel D Kuns, Peter Fleming, Kelly R Locke, Nicholas D Huntington, Bruce R Blazar, Steven W Lane, Siok-Keen Tey, Kelli P A MacDonald, Mark J Smyth, Mariapia A Degli-Esposti, Geoffrey R Hill
Allogeneic bone marrow transplantation (allo-BMT) is a curative therapy for hematological malignancies, but is associated with significant complications, principally graft-versus-host disease (GVHD) and opportunistic infections. Natural killer (NK) cells mediate important innate immunity that provides a temporal bridge until the reconstruction of adaptive immunity. Here we show that the development of GVHD after allo-BMT prevented NK-cell reconstitution, particularly within the maturing M1 and M2 NK-cell subsets in association with exaggerated activation, apoptosis and autophagy...
December 7, 2016: Blood
https://www.readbyqxmd.com/read/27890260/the-role-of-second-transplants-for-leukemia
#9
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
#10
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
#11
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
#12
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 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 transplant (HCT) 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...
December 22, 2016: Blood
https://www.readbyqxmd.com/read/27788764/haploidentical-cord-transplantation-the-best-of-both-worlds
#13
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
#14
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
#15
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
#16
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 Society for Blood and Marrow Transplantation centers...
January 2017: 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
#17
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...
January 2017: 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
#18
REVIEW
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
#19
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
#20
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
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