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https://www.readbyqxmd.com/read/29317998/new-and-emerging-therapies-for-acute-and-chronic-graft-versus-host-disease
#1
REVIEW
LaQuisa Hill, Amin Alousi, Partow Kebriaei, Rohtesh Mehta, Katayoun Rezvani, Elizabeth Shpall
Graft versus host disease (GVHD) remains a major cause of morbidity and mortality following allogeneic hematopoietic stem-cell transplantation (HSCT). Despite the use of prophylactic GVHD regimens, a significant proportion of transplant recipients will develop acute or chronic GVHD following HSCT. Corticosteroids are standard first-line therapy, but are only effective in roughly half of all cases with ~50% of patients going on to develop steroid-refractory disease, which increases the risk of nonrelapse mortality...
January 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29301771/off-the-shelf-tcr-for-graft-versus-leukemia-without-gvhd
#2
Frederick L Locke, Claudio Anasetti
No abstract text is available yet for this article.
January 4, 2018: Blood
https://www.readbyqxmd.com/read/29296800/the-number-of-cd56dim-nk-cells-in-the-graft-has-a-major-impact-on-risk-of-disease-relapse-following-allo-hsct
#3
Luke Maggs, Francesca Kinsella, Y L Tracey Chan, Suzy Eldershaw, Duncan Murray, Jane Nunnick, Joanne Bird, Charles Craddock, Jianmin Zuo, Ram Malladi, Paul Moss
The graft-versus-leukemia (GVL) effect of allogeneic hemopoietic stem cell transplantation (allo-HSCT) is mediated by the donor immune system and acts to decrease the rate of disease relapse. Although studies of posttransplant immune reconstitution have identified correlates of clinical outcome, the number and profile of mature immune cells infused with the stem cell graft is also likely to be an important determinant and has been relatively poorly studied. We characterized immune cells within the stem cell graft of 107 patients who underwent T-cell-depleted allo-HSCT and related this to clinical outcome...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/29289756/the-role-of-janus-kinase-signaling-in-graft-versus-host-disease-and-graft-versus-leukemia
#4
REVIEW
Mark A Schroeder, Jaebok Choi, Karl Staser, John F DiPersio
For patients with hematologic malignancies, allogeneic hematopoietic cell transplantation (alloHCT) offers a potential curative treatment option, primarily due to an allogeneic immune response against recipient tumor cells (ie, graft-versus-leukemia [GVL] activity). However, many recipients of alloHCT develop graft-versus-host disease (GVHD), in which allogeneic immune responses lead to the damage of healthy tissue. GVHD is a leading cause of nonrelapse mortality and a key contributor to morbidity among patients undergoing alloHCT...
December 28, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29283907/when-should-patients-receive-consolidation-chemotherapy-before-allogeneic-hematopoietic-cell-transplantation-for-acute-myeloid-leukemia-in-first-complete-remission
#5
Moshe Yeshurun, Ofir Wolach
PURPOSE OF REVIEW: Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative therapy for patients with acute myeloid leukemia. Despite the associated graft-versus-leukemia effect, leukemia relapse remains the most common cause of treatment failure after alloHCT. Here, we review the available data on whether there is an advantage in providing pretransplant consolidation chemotherapy prior to alloHCT. RECENT FINDINGS: Randomized controlled studies are lacking...
December 27, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29282719/il-12-il-18-preactivated-donor-nk-cells-enhance-gvl-effects-and-mitigate-gvhd-after-allogeneic-hematopoietic-stem-cell-transplantation
#6
Yuan Song, Bo Hu, Yonghao Liu, Ziqi Jin, Yinsheng Zhang, Dandan Lin, Ying Zhu, Lei Lei, Huanle Gong, Yu Mei, Huey Yee Teo, Depei Wu, Haiyan Liu
Adoptive transfer of donor NK cells has the potential of mediating graft-versus-leukemia (GVL) effect while suppressing acute graft-versus-host-disease (aGVHD) during allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, these beneficial effects are limited by the transient function of adoptively transferred NK cells. Previous studies demonstrate that cytokine-induced memory-like NK cells that are preactivated by IL-12, IL-15, and IL-18 have enhanced effector functions and long life span in vivo...
December 27, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29251415/specific-t-cell-responses-against-minor-histocompatibility-antigens-cannot-generally-be-explained-by-absence-of-their-allelic-counterparts-on-the-cell-surface
#7
Helena Maria Bijen, Chopie Hassan, Michel G D Kester, George M C Janssen, Pleun Hombrink, Arnoud H de Ru, Jan Wouter Drijfhout, Hugo D Meiring, Ad P de Jong, J H Frederik Falkenburg, Connie R Jimenez, Mirjam H M Heemskerk, Peter A van Veelen
Allogeneic stem cell transplantation has emerged as immunotherapy in the treatment of a variety of hematological malignancies. Its efficacy depends on induction of graft versus leukemia by donor lymphocytes. Both graft versus leukemia and graft versus host disease are induced by T-cells reactive against polymorphic peptides, called minor histocompatibility antigens (MiHA), which differ between patient and donor and are presented in the context of self-HLA. The allelic counterpart (AC) of the MiHA is generally considered to be absent at the cell surface, based on the absence of immune responses directed against the AC...
December 18, 2017: Proteomics
https://www.readbyqxmd.com/read/29232687/photochemotherapy-and-graft-versus-leukemia-reaction-in-acute-leukemia-tumor-immunity-and-survival-are-dependent-on-timing-of-photochemotherapy-of-the-skin
#8
Nicolas Feldreich, Olle Ringden, Lennart Emtestam
BACKGROUND: Cure of acute leukemia after transplantation is mediated by the grafted cells. We investigated the graft-versus-leukemia effect (GVL) in patients with cutaneous acute graft-versus-host disease (GVHD) treated with photochemotherapy (psoralen and ultraviolet light type A). METHOD: Forty-seven patients with acute leukemia were followed 5,000 days after transplantation to assess survival and GVL by multivariate analysis. The primary predictor was time to treatment of cutaneous acute GVHD by photochemotherapy separated into treatment start during the first week of acute GVHD versus after the first week of acute GVHD...
December 13, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/29212976/-congenital-leukemia-showing-lineage-switch-following-induction-chemotherapy-and-attaining-long-term-remission-after-hla-haploidentical-stem-cell-transplantation
#9
Kazuki Furudate, Yuri Okimoto, Kumiko Ando, Yuichi Taneyama, Hidemasa Ochiai, Harumi Kakuda
Congenital leukemia is a rare subgroup of childhood leukemia. Lineage switches in leukemic cells are relatively rare events, which have been occasionally reported in congenital leukemia. To the best of our knowledge, the survival of congenital leukemia patients with lineage switch has not been previously documented. This lack of documentation may be attributable to extremely poor prognosis of these patients. We describe a case of a newborn female with initial diagnosis of MLL-AF4 positive B-precursor acute lymphoblastic leukemia, who developed lineage switch to acute monocytic leukemia following the induction therapy...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29209333/inhibition-of-acute-graft-versus-host-disease-with-retention-of-graft-versus-tumor-effects-by-dimethyl-fumarate
#10
Jingjing Han, Shoubao Ma, Huanle Gong, Shuangzhu Liu, Lei Lei, Bo Hu, Yang Xu, Haiyan Liu, Depei Wu
Acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF), an activator of Nrf2, has been shown to have anti-inflammatory and immunomodulatory properties without significant immunosuppression. We therefore hypothesized that DMF could be potentially harnessed for the treatment of aGVHD with retention of graft-versus-tumor effect. In this study, we showed that DMF significantly inhibited alloreactive T cell responses in vitro in mixed lymphocyte reaction assay...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29197675/homozygous-hla-c1-is-associated-with-reduced-risk-of-relapse-after-hla-matched-transplantation-in-patients-with-myeloid-leukemia
#11
Nobuyoshi Arima, Junya Kanda, Junji Tanaka, Toshio Yabe, Yasuo Morishima, Sung-Won Kim, Yuho Najima, Yukiyasu Ozawa, Tetsuya Eto, Heiwa Kanamori, Takehiko Mori, Naoki Kobayashi, Tadakazu Kondo, Hirohisa Nakamae, Naoyuki Uchida, Masami Inoue, Takahiro Fukuda, Tatsuo Ichinohe, Yoshiko Atsuta, Yoshinobu Kanda
Natural killer (NK) cells assume graft-versus-leukemia alloreactivity after hematopoietic stem cell transplantation (HSCT) through their inhibitory killer cell immunoglobulin-like receptors (KIRs). KIR2D family members recognize HLA-C alleles with Asn80 (HLA-C1) or Lys80 (HLA-C2). The predominance of HLA-C1 over HLA-C2 and the frequent presence of KIR2DL1 are characteristic of Japanese people. We compared clinical outcomes among homozygous HLA-C1 (HLA-C1/C1) patients and heterozygous HLA-C1/C2 patients who underwent HLA-matched HSCT for hematologic malignancies by assessing the data of 10,638 patients from the Japanese national registry...
December 27, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29156205/which-factors-influence-the-development-of-gvhd-in-hla-matched-or-mismatched-transplants
#12
REVIEW
Effie W Petersdorf
The sheer diversity of HLA alleles makes the probability of finding matched unrelated donors for patients requiring hematopoietic cell transplantation (HCT) a complex situation. New evidence suggests that mismatching at certain HLA loci may provide a greater benefit in terms of graft-versus-leukemia effect than other mismatches when HLA-matched donors are not available. This review summarizes the current understanding of HLA matching requirements for unrelated donor HCT.
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29156204/autologous-hematopoietic-cell-transplantation-for-adult-acute-myeloid-leukemia-an-obsolete-or-resurfacing-concept
#13
REVIEW
Hillard M Lazarus, Najla El Jurdi
Improving long-term outcomes of adult acute myeloid leukemia (AML) patients remains a challenge. Major scientific and clinical advances have led to a better understanding of the disease biology, and the majority of patients achieve a complete remission (CR) after induction therapy. Relapse risk, however, remains considerable and is the leading cause of death in this patient population. Significant efforts to improve outcomes emphasize use of post-remission therapies such as hematopoietic cell transplantation (HCT), an increasingly utilized modality...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29061569/aml-specific-cytotoxic-antibodies-in-patients-with-durable-graft-versus-leukemia-responses
#14
Marijn A Gillissen, Martijn Kedde, Greta de Jong, Gemma Moiset, Etsuko Yasuda, Sophie E Levie, Arjen Q Bakker, Yvonne B Claassen, Koen Wagner, Martino Böhne, Paul J Hensbergen, Dave Speijer, Pauline M van Helden, Tim Beaumont, Hergen Spits, Mette D Hazenberg
Most acute myeloid leukemia (AML) patients can only be cured when an allogeneic hematopoietic stem cell transplantation (HSCT) induces a graft versus leukemia immune response (GvL). While the role of T cells and NK cells in tumor immunology has been established, less is known about the contribution of B cells. From B cells of high-risk AML patients with potent and lasting GvL responses we isolated monoclonal antibodies directed against antigens expressed on the cell surface of AML cells but not on normal hematopoietic and non-hematopoietic cells...
October 23, 2017: Blood
https://www.readbyqxmd.com/read/29038366/specifically-differentiated-t-cell-subset-promotes-tumor-immunity-over-fatal-immunity
#15
Abdulraouf Ramadan, Brad Griesenauer, Djamilatou Adom, Reuben Kapur, Helmut Hanenberg, Chen Liu, Mark H Kaplan, Sophie Paczesny
Allogeneic immune cells, particularly T cells in donor grafts, recognize and eliminate leukemic cells via graft-versus-leukemia (GVL) reactivity, and transfer of these cells is often used for high-risk hematological malignancies, including acute myeloid leukemia. Unfortunately, these cells also attack host normal tissues through the often fatal graft-versus-host disease (GVHD). Full separation of GVL activity from GVHD has yet to be achieved. Here, we show that, in mice and humans, a population of interleukin-9 (IL-9)-producing T cells activated via the ST2-IL-33 pathway (T9IL-33 cells) increases GVL while decreasing GVHD through two opposing mechanisms: protection from fatal immunity by amphiregulin expression and augmentation of antileukemic activity compared with T9, T1, and unmanipulated T cells through CD8α expression...
October 16, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29032274/assessment-of-impact-of-hla-type-on-outcomes-of-allogeneic-hematopoietic-stem-cell-transplantation-for-chronic-lymphocytic-leukemia
#16
Brian T Hill, Kwang Woo Ahn, Zhen-Huan Hu, Mahmoud Aljurf, Amer Beitinjaneh, Jean-Yves Cahn, Jan Cerny, Mohamed A Kharfan-Dabaja, Siddhartha Ganguly, Nilanjan Ghosh, Michael R Grunwald, Yoshihiro Inamoto, Tamila Kindwall-Keller, Taiga Nishihori, Richard F Olsson, Ayman Saad, Matthew Seftel, Sachiko Seo, Jeffrey Szer, Martin Tallman, Celalettin Ustun, Peter H Wiernik, Richard T Maziarz, Matt Kalaycio, Edwin Alyea, Uday Popat, Ronald Sobecks, Wael Saber
Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplantation (allo-HCT) for medically fit patients. Although the use of allo-HCT has declined since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT, the sole known curative treatment for CLL...
October 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28991134/isolated-testicular-recurrence-of-aml-in-patients-with-chronic-gvhd-1-year-following-allogeneic-stem-cell-transplant
#17
Brian N Dang, Satiro De Oliveira, LaVette Bowles, Theodore B Moore
BACKGROUND: Patients with chronic graft-versus-host disease (cGVHD) following allogeneic transplant for myeloid leukemias seem to experience a reduced risk of relapse than comparable patients without cGVHD. It is unclear to what extent extramedullary sites are impacted by a graft-versus-leukemia effect. DESIGN/METHOD: Case Series and review of the literature. RESULTS: We present 2 cases of pediatric patients with Acute Myelogenous Leukemia who developed isolated testicular relapse more than a year following hematopoietic stem cell transplantation despite having had extensive cGVHD...
November 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28977716/occurrence-of-graft-versus-host-disease-increases-mortality-after-umbilical-cord-blood-transplantation-for-acute-myeloid-leukemia-a-report-from-eurocord-and-the-alwp-of-the-ebmt
#18
Frédéric Baron, Annalisa Ruggeri, Eric Beohou, Myriam Labopin, Mohamad Mohty, Jaime Sanz, Stephane Vigouroux, Sabine Furst, Alberto Bosi, Patrice Chevallier, Jan J Cornelissen, Mauricette Michallet, Jorge Sierra, Dimitrios Karakasis, Bipin N Savani, Eliane Gluckman, Arnon Nagler
BACKGROUND: The efficacy of umbilical cord blood transplantation (UCBT) as treatment for acute myeloid leukemia (AML) relies on immune-mediated graft-versus-leukemia effects. Previous studies have suggested a strong association between graft-versus-host disease (GVHD) occurrence and graft-versus-leukemia effects after allogeneic hematopoietic cell transplantation. METHODS: Here, we evaluated the kinetics of relapse rate in correlation to GVHD occurrence after UCBT...
October 4, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28971902/mixed-phenotype-acute-leukemia-outcomes-with-allogeneic-stem-cell-transplantation-a-retrospective-study-from-the-acute-leukemia-working-party-of-the-ebmt
#19
Reinhold Munker, Myriam Labopin, Jordi Esteve, Christoph Schmid, Mohamad Mohty, Arnon Nagler
Mixed phenotype acute leukemias are infrequent and considered high-risk. The optimal treatment approach and the role of allogeneic hematopoietic stem cell transplantation are not entirely clear. In this study, we investigated 519 patients with mixed phenotype acute leukemia in first complete remission who underwent allogeneic hematopoietic stem cell transplantation between 2000 and 2014 and were reported to the Acute Leukemia Working Party of the EBMT. The median age was 38.1 years (range 18- 75), by cytogenetics, 49...
September 29, 2017: Haematologica
https://www.readbyqxmd.com/read/28959694/use-of-rapamycin-in-a-patient-with-juvenile-myelomonocytic-leukemia-a-case-report
#20
Shivani Y Upadhyay, Satiro N De Oliveira, Theodore B Moore
The relapse rate for children with juvenile myelomonocytic leukemia (JMML) status post hematopoietic stem cell transplantation (HSCT) approaches 50% within 5 years. Graft-versus-leukemia (GVL) is thought to play important role in the treatment of JMML. For this reason, careful management of immunosuppressive drugs after HSCT is crucial. This case report demonstrates that rapamycin and GVL represent a viable medical strategy for the management of pediatric patients with JMML who relapse following status post-HSCT...
July 2017: Journal of Investigative Medicine High Impact Case Reports
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