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https://www.readbyqxmd.com/read/28229282/clinical-studies-in-hematologic-microtransplantation
#1
REVIEW
Kevin A David, Dennis Cooper, Roger Strair
The anti-tumor effects of allogeneic hematopoietic stem cell transplantation depend upon engraftment of donor cells followed by a graft-versus-tumor (GVT) effect. However, pre-clinical and clinical studies have established that under certain circumstances, anti-tumor responses can occur despite the absence of high levels of durable donor cell engraftment. Tumor response with little or no donor engraftment has been termed "microtransplantation." It has been hard to define conditions leading to tumor responses without donor cell persistence in humans because the degree of engraftment depends very heavily upon many patient-specific factors, including immune status and degree of prior therapy...
February 22, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28064242/cyclin-dependent-kinase-5-activity-is-required-for-allogeneic-t-cell-responses-after-hematopoietic-cell-transplantation-in-mice
#2
David Askew, Tej K Pareek, Saada Eid, Sudipto Ganguly, Megan Tyler, Alex Y Huang, John J Letterio, Kenneth R Cooke
Molecular intermediates in T-cell activation pathways are crucial targets for the therapy and prevention of graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (allo-HCT). We recently identified an essential role for cyclin-dependent kinase 5 (Cdk5) in T-cell activation and effector function, but the contribution of Cdk5 activity to the development of GVHD has not been explored. Using an established, preclinical, murine, GVHD model, we reveal that Cdk5 activity is increased in key target organs early after allo-HCT...
January 12, 2017: Blood
https://www.readbyqxmd.com/read/28058217/review-of-allogeneic-hematopoietic-stem-cell-transplantation-with-reduced-intensity-conditioning-in-solid-tumors-excluding-breast-cancer
#3
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/28012219/incorporation-of-high-dose-131-i-metaiodobenzylguanidine-treatment-into-killer-immunoglobulin-like-receptor-hla-ligand-mismatched-haploidentical-stem-cell-transplantation-for-children-with-neuroblastoma-who-failed-tandem-autologous-stem-cell-transplantation
#4
Ji Won Lee, Eun-Suk Kang, Ki Woong Sung, Eunsang Yi, Soo Hyun Lee, Keon Hee Yoo, Hong Hoe Koo
BACKGROUND: We performed a pilot study (NCT 00793351) to evaluate the effectiveness and feasibility of a strategy incorporating high-dose (131) I-metaiodobenzylguanidine (HD-MIBG) treatment into killer immunoglobulin-like receptor (KIR)/HLA-ligand mismatched haploidentical stem cell transplantation (haplo-SCT) in improving the survival of children with neuroblastoma who failed previous tandem autologous SCT. PROCEDURE: If the patient remained progression free with salvage treatment, HD-MIBG treatment (18 mCi/kg) was given prior to reduced-intensity conditioning (cyclophosphamide + fludarabine + antithymocyte globulin)...
December 24, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27997582/-gt-n-repeat-polymorphism-in-heme-oxygenase-1-ho-1-correlates-with-clinical-outcome-after-myeloablative-or-nonmyeloablative-allogeneic-hematopoietic-cell-transplantation
#5
Tania Køllgaard, Brian Kornblit, Jesper Petersen, Tobias Wirenfeldt Klausen, Bo Kok Mortensen, Peter Brændstrup, Henrik Sengeløv, Estrid Høgdall, Klaus Müller, Lars Vindeløv, Mads Hald Andersen, Per Thor Straten
Allogeneic hematopoietic cell transplantation (HCT) is a treatment for various hematologic diseases where efficacy of treatment is in part based on the graft versus tumour (GVT) activity of cells in the transplant. The cytoprotective enzyme heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme degradation and it has been shown to exert anti-inflammatory functions. In humans a (GT)n repeat polymorphism regulates the expression of HO-1. We conducted fragment length analyses of the (GT)n repeat in the promotor region of the gene for HO-1 in DNA from donors and recipients receiving allogeneic myeloablative- (MA) (n = 110) or nonmyeloablative- (NMA-) (n = 250) HCT...
2016: PloS One
https://www.readbyqxmd.com/read/27980780/hsp90-inhibition-ameliorates-cd4-t-cell-mediated-acute-graft-versus-host-disease-in-mice
#6
Carsten Berges, Thomas Kerkau, Sandra Werner, Nelli Wolf, Nadine Winter, Thomas Hünig, Hermann Einsele, Max S Topp, Niklas Beyersdorf
INTRODUCTION: For many patients with leukemia only allogeneic bone marrow transplantion provides a chance of cure. Co-transplanted mature donor T cells mediate the desired Graft versus Tumor (GvT) effect required to destroy residual leukemic cells. The donor T cells very often, however, also attack healthy tissue of the patient inducing acute Graft versus Host Disease (aGvHD)-a potentially life-threatening complication. METHODS: Therefore, we used the well established C57BL/6 into BALB/c mouse aGvHD model to evaluate whether pharmacological inhibition of heat shock protein 90 (Hsp90) would protect the mice from aGvHD...
December 2016: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/27941492/effects-of-a-modified-german-volume-training-program-on-muscular-hypertrophy-and-strength
#7
Theban Amirthalingam, Yorgi Mavros, Guy C Wilson, Jillian L Clarke, Lachlan Mitchell, Daniel A Hackett
German Volume Training (GVT), or the 10 sets method, has been used for decades by weightlifters to increase muscle mass. To date, no study has directly examined the training adaptations following GVT. The purpose of this study was to investigate the effect of a modified GVT intervention on muscular hypertrophy and strength. Nineteen healthy males were randomly assign to 6 weeks of 10 or 5 sets of 10 repetitions for specific compound resistance exercises included in a split-routine performed 3 times per week...
November 25, 2016: Journal of Strength and Conditioning Research
https://www.readbyqxmd.com/read/27872095/t-cells-redirected-to-a-minor-histocompatibility-antigen-instruct-intratumoral-tnf%C3%AE-expression-and-empower-adoptive-cell-therapy-for-solid-tumors
#8
Teresa Manzo, Tabea Sturmheit, Veronica Basso, Elisabetta Petrozziello, Rodrigo Hess Michelini, Michela Riba, Massimo Freschi, Angela R Elia, Matteo Grioni, Flavio Curnis, Maria Pia Protti, Ton N Schumacher, Reno Debets, Melody A Swartz, Angelo Corti, Matteo Bellone, Anna Mondino
Donor-derived allogeneic T cells evoke potent graft versus tumor (GVT) effects likely due to the simultaneous recognition of tumor-specific and host-restricted minor histocompatibility (H) antigens. Here we investigated whether such effects could be reproduced in autologous settings by TCR gene-engineered lymphocytes. We report that T cells redirected either to a broadly expressed Y-encoded minor H antigen or to a tumor-associated antigen, although poorly effective if individually transferred, when simultaneously administered enabled acute autochthonous tumor debulking and resulted in durable clinical remission...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27815049/therapeutic-effects-of-a-nedd8-activating-enzyme-inhibitor-pevonedistat-on-sclerodermatous-graft-versus-host-disease-in-mice
#9
Chien-Chun Steven Pai, Lam T Khuat, Mingyi Chen, William J Murphy, Mehrdad Abedi
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole treatment option for highly malignant hematologic disease; however, the major complication-graft-versus-host disease (GVHD)-still hinders its clinical application. In addition, chronic GVHD remains the major cause of long-term morbidity and mortality after allo-HSCT. Previously we showed that bortezomib, a proteasome inhibitor, can ameliorate the sclerodermatous GVHD response while maintaining graft-versus-tumor (GVT) effects. Here we report that pevonedistat (MLN4924), an inhibitor of the Nedd8-activating enzyme, which functions upstream of the proteasome in the ubiquitin-proteasome pathway, can also show similar protective effects...
January 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27774524/granzyme-b-contributes-to-the-optimal-graft-versus-tumor-effect-mediated-by-conventional-cd4-t-cells
#10
Wei Du, Nicholas D Leigh, Guanglin Bian, Emad Alqassim, Rachel E O'Neill, Lin Mei, Jingxin Qiu, Hong Liu, Philip L McCarthy, Xuefang Cao
Granzyme B (GzmB) is a key cytotoxic molecule utilized by T cells to kill pathogen-infected cells or transformed tumor cells. Previous studies using allogeneic hematopoietic cell transplantation (allo-HCT) murine models showed that GzmB is required for CD8(+) T cells to cause graft-versus-host disease (GVHD). However, our recent study demonstrated that GzmB-mediated damage of CD8(+) T cells diminished their graft-versus-tumor (GVT) activity. In this study, we examined the role of GzmB in GVT effect mediated by conventional CD4(+)CD25(-) T cells (CD4(+) Tcon)...
2016: Journal of Immunology Research and Therapy
https://www.readbyqxmd.com/read/27699218/the-mek-inhibitor-trametinib-separates-murine-graft-versus-host-disease-from-graft-versus-tumor-effects
#11
Hidekazu Itamura, Takero Shindo, Isao Tawara, Yasushi Kubota, Ryusho Kariya, Seiji Okada, Krishna V Komanduri, Shinya Kimura
The efficacy of allogeneic hematopoietic stem cell transplantation for hematologic malignancies is limited by the difficulty in suppressing graft-versus-host disease (GVHD) without compromising graft-versus-tumor (GVT) effects. We previously showed that RAS/MEK/ERK signaling depends on memory differentiation in human T cells, which confers susceptibility to selective inhibition of naive T cells. Actually, antineoplastic MEK inhibitors selectively suppress alloreactive T cells, sparing virus-specific T cells in vitro...
July 7, 2016: JCI Insight
https://www.readbyqxmd.com/read/27587310/safety-and-efficacy-of-transplantation-with-allogeneic-skin-tumors-to-treat-chemically-induced-skin-tumors-in-mice
#12
Zhiwei Zhang, Hua Sun, Jianhua Zhang, Chunlei Ge, Suwei Dong, Zhen Li, Ruilei Li, Xiaodan Chen, Mei Li, Yun Chen, Yingying Zou, Zhongyi Qian, Lei Yang, Jinyan Yang, Zhitao Zhu, Zhimin Liu, Xin Song
BACKGROUND Transplantation with allogeneic cells has become a promising modality for cancer therapy, which can induce graft-versus-tumor (GVT) effect. This study was aimed at assessing the safety, efficacy, and tissue type GVT (tGVT) response of transplantation with allogeneic skin tumors to treat chemically-induced skin tumors in mice. MATERIAL AND METHODS FVB/N and ICR mice were exposed topically to chemicals to induce skin tumors. Healthy ICR mice were transplanted with allogeneic skin tumors from FVB/N mice to test the safety...
September 2, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27447780/recombinant-il-7-hgf%C3%AE-hybrid-cytokine-separates-acute-graft-versus-host-disease-from-graft-versus-tumour-activity-by-altering-donor-t-cell-trafficking
#13
Rong Hu, Yalan Liu, Yinhong Song, Min Su, Xiuling Lu, Debra Rood, Laijun Lai
Given that donor T cells from a transplant contribute both the desired graft-versus-tumour (GVT) effect and detrimental graft-versus-host disease (GVHD), strategies to separate GVHD and GVT activity are a major clinical goal. We have previously demonstrated that in vivo administration of a recombinant (r)IL-7/HGFβ hybrid cytokine, consisting of interleukin-7 (IL-7, IL7) and the β-chain of hepatocyte growth factor (HGFβ), significantly inhibits the growth of cancer cells in murine tumour models. The antit-umour effect of rIL-7/HGFβ is related to a marked infiltration T cells in the tumour tissues...
July 22, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27319051/pgp-potential-abiotic-stress-tolerance-and-antifungal-activity-of-azotobacter-strains-isolated-from-paddy-soils
#14
G Chennappa, M K Naik, C R Adkar-Purushothama, Y S Amaresh, M Y Sreenivasa
Azotobacter strains were isolated by serial dilution method and colonies were viscous, smooth, glistening, and brown to black colour on Jenson's N-free agar. Morphological and biochemical tests showed characteristic features of Azotobacter. Further, molecular analyses revealed the presence of different Azotobacter species viz., A. armeniacus, A. chroococcum, A. salinestris, A. tropicalis and A. vinelandii. The isolates were tested for their ability of nitrogen fixation, indole acetic acid (IAA), gibberllic acid production and phosphate solubilization...
May 2016: Indian Journal of Experimental Biology
https://www.readbyqxmd.com/read/27118383/ctla-4-polymorphisms-and-haplotype-correlate-with-survival-in-all-after-allogeneic-stem-cell-transplantation-from-related-hla-haplotype-mismatched-donor
#15
X-Y Qin, Y Wang, G-X Li, Y-Z Qin, F-R Wang, L-P Xu, H Chen, W Han, J-Z Wang, X-H Zhang, Y-J Chang, K-Y Liu, Z-F Jiang, X-J Huang
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been established as an effective treatment for patients with hematological malignancies. Disease relapse remains a major cause of transplant failure. T cell homeostasis is critical to determine the potency of the GVT effect. Recent studies have shown the association of the CTLA-4 polymorphisms with the outcome after HLA-identical sibling allogeneic HSCT. METHODS: In this study, we focused on four CTLA-4 polymorphisms, and analyzed the impact of donor genotypes and haplotypes on the conditions of 152 acute leukemia patients (ALL 83) after related HLA-haplotype- mismatched transplantation...
April 27, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27066008/bone-marrow-gvhd-after-allogeneic-hematopoietic-stem-cell-transplantation
#16
REVIEW
Martin Szyska, Il-Kang Na
The bone marrow is the origin of all hematopoietic lineages and an important homing site for memory cells of the adaptive immune system. It has recently emerged as a graft-versus-host disease (GvHD) target organ after allogeneic stem cell transplantation (alloHSCT), marked by depletion of both hematopoietic progenitors and niche-forming cells. Serious effects on the restoration of hematopoietic function and immunological memory are common, especially in patients after myeloablative conditioning therapy. Cytopenia and durable immunodeficiency caused by the depletion of hematopoietic progenitors and destruction of bone marrow niches negatively influence the outcome of alloHSCT...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/26595077/new-strategies-of-dli-in-the-management-of-relapse-of-hematological-malignancies-after-allogeneic-hematopoietic-sct
#17
REVIEW
X Chang, X Zang, C Q Xia
DLI is an effective strategy for patients with recurrent hematological malignancies after allogeneic hematopoietic SCT (allo-HSCT). DLI has been widely applied to boost the graft vs tumor (GVT) or GVL effects. However, given the potentially severe complications associated with conventional DLI and transient GVL effect, new strategies for DLI are emerging. In this review, we have discussed the recent important studies on DLI as a prophylactic or therapeutic modality for relapsed hematological disorders after allo-HSCT...
March 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/26319093/predicted-indirectly-recognizable-hla-epitopes-class-i-promote-antileukemia-responses-after-cord-blood-transplantation-indications-for-a-potential-novel-donor-selection-tool
#18
Kirsten A Thus, Talitha A de Hoop, Roel A de Weger, Marc B Bierings, Jaap Jan Boelens, Eric Spierings
Unrelated cord blood transplantation (UCBT) provides a curative therapy for patients with hematological malignancies. The effect of HLA mismatches in UCBT is currently the subject of debate. HLA-mismatched UCBT may lead to improved leukemia control but also to graft-versus-host disease (GVHD), resulting in nonrelapse mortality (NRM). The aim of this study was to investigate whether indirect recognition of mismatched HLA provides an explanation for the graft-versus-tumor effect and risk of GVHD. The probability of indirect recognition was predicted by the Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) model...
January 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/26187863/cd34-selected-hematopoietic-stem-cell-transplants-conditioned-with-myeloablative-regimens-and-antithymocyte-globulin-for-advanced-myelodysplastic-syndrome-limited-graft-versus-host-disease-without-increased-relapse
#19
Roni Tamari, Stephen S Chung, Esperanza B Papadopoulos, Ann A Jakubowski, Patrick Hilden, Sean M Devlin, Jenna D Goldberg, Miguel-Angel Perales, Doris M Ponce, Craig S Sauter, Molly A Maloy, Dara Y Herman, Virginia Klimek, James W Young, Richard J O'Reilly, Sergio A Giralt, Hugo Castro-Malaspina
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for patients with myelodysplastic syndrome (MDS). Donor T cells are critical for the graft-versus-tumor effect but carry the risk of graft-versus-host disease (GVHD). CD34 selection with immunomagnetic beads has been an effective method of depleting alloreactive donor T cells from the peripheral blood graft and has been shown to result in significant reduction in acute and chronic GVHD. We analyzed the outcomes of 102 adults (median age, 57...
December 2015: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/26138178/fqrs-as-a-marker-of-granulomatous-disease-in-patients-presenting-with-ventricular-tachycardia-and-normal-left-ventricular-ejection-fraction
#20
Henri Roukoz, Mandar Shah, Lawrence Jesuraj Masilamani, Ajit Thachil, Prem K Jayakumar, David G Benditt, Calambur Narasimhan
BACKGROUND: Granulomatous myocarditis may present with sustained monomorphic ventricular tachycardia (SMVT) in the presence of normal left ventricular ejection fraction (LVEF), and could be mistaken for idiopathic ventricular tachycardia (IVT). The use of cardiac imaging for diagnosis can be limited by availability and high cost. ECG is readily available and inexpensive. Fragmented QRS (fQRS) on ECG has been found to be associated with myocardial scar. We hypothesized that fQRS could be useful in the diagnosis of granulomatous VT (GVT)...
May 2015: Indian Heart Journal
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