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T-cells, hematopoietic cell transplant

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https://www.readbyqxmd.com/read/27933342/prediction-of-nk-cell-licensing-level-in-selection-of-hematopoietic-stem-cell-donor-initial-results
#1
Marta Rogatko-Koroś, Renata Mika-Witkowska, Katarzyna Bogunia-Kubik, Barbara Wysoczańska, Emilia Jaskuła, Katarzyna Kościńska, Klaudia Nestorowicz, Joanna Dziopa, Urszula Szlendak, Sławomir Gwozdowicz, Elżbieta Graczyk-Pol, Andrzej Lange, Jacek Nowak
Natural killer (NK) cell licensing status depends on clonal expression of inhibitory killer cell immunoglobulin-like receptors (iKIR) and short term HLA environment. Licensed NK cells are more efficient in tumor killing than unlicensed NK cells. Cognate KIR-HLA pairs in hematopoietic stem cell transplant (HSCT) donor and recipient are decisive for the possible change in the NK cell licensing status after HSCT. We assessed clinical outcomes in 297 patients with lymphoproliferative or myeloproliferative malignancies, or myelodysplastic syndrome in a model with upward licensing, downward resetting, and unchanged licensing genetics status after T cell replate HSCT from unrelated donors...
December 8, 2016: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/27933316/systemic-therapy-with-oncolytic-myxoma-virus-cures-established-residual-multiple-myeloma-in-mice
#2
Eric Bartee, Mee Y Bartee, Bjarne Bogen, Xue-Zhong Yu
Multiple myeloma is an incurable malignancy of plasma B-cells. Traditional chemotherapeutic regimes often induce initial tumor regression; however, virtually all patients eventually succumb to relapse caused by either reintroduction of disease during autologous transplant or expansion of chemotherapy resistant minimal residual disease. It has been previously demonstrated that an oncolytic virus known as myxoma can completely prevent myeloma relapse caused by reintroduction of malignant cells during autologous transplant...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27932187/successful-t-cell-replete-hematopoietic-stem-cell-boost-without-conditioning-for-late-graft-failure
#3
Y Tsutsumi, T Tateno, S Ito, S Shiratori, T Teshima
Late graft failure is a rare but significant complication after allogeneic stem cell transplantation, which is often complicated by severe infections. We report a case of late graft failure, which was successfully treated with a T-cell replete hematopoietic stem cell boost without conditioning that induced rapid engraftment and relieved the patient of infection. Discontinuation of immunosuppressants and nilotinib administration suppressed the host cells. Achieving full donor chimerism allowed us to administer a peripheral blood stem cell boost without conditioning...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27932175/first-attempt-of-sequential-living-donor-liver-and-hematopoietic-stem-cell-transplantation-in-a-child-with-advanced-hepatocellular-carcinoma-case-report
#4
J A Picoraro, N Ovchinsky, M Martinez, S J Lobritto, P Satwani, R Ramphal, M S Cairo, T Kato
Effective therapeutic options for advanced hepatocellular carcinoma are limited. Hematopoietic stem cell transplantation may offer a graft-versus-tumor effect. Combined liver and hematopoietic stem cell transplantation from the same donor with preparatory conditioning may promote tolerogenicity to the liver allograft and offers the potential for immunosuppression withdrawal. We report our experience with the use of this approach in a pediatric patient with invasive hepatocellular carcinoma and pulmonary metastases who underwent a living-donor liver transplantation followed by reduced-toxicity myeloablative conditioning and hematopoietic stem cell transplant from the same parental donor...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27931534/advances-in-clinical-immunology-in-2015
#5
REVIEW
Javier Chinen, Luigi D Notarangelo, William T Shearer
Advances in clinical immunology in the past year included the report of practice parameters for the diagnosis and management of primary immunodeficiencies to guide the clinician in the approach to these relatively uncommon disorders. We have learned of new gene defects causing immunodeficiency and of new phenotypes expanding the spectrum of conditions caused by genetic mutations such as a specific regulator of telomere elongation (RTEL1) mutation causing isolated natural killer cell deficiency and mutations in ras-associated RAB (RAB27) resulting in immunodeficiency without albinism...
December 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27931306/idiopathic-cd4-lymphocytopenia
#6
Joel P Brooks, Gisoo Ghaffari
BACKGROUND: Idiopathic CD4 lymphocytopenia (ICL) is a rare disorder of unknown etiology. Diagnostic criteria include a persistent CD4 T-cell lymphopenia with no underlying primary or secondary immune deficiencies and a CD4 T-cell count of 300 cells/mL or 20% total lymphocyte on multiple occasions. OBJECTIVE: To increase awareness of ICL and to provide a review of the clinical characteristics, diagnosis, and management of this disease process. Presently, many of these patients receive prophylactic treatment similar to other T-cell deficient conditions, most notably patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome; however, the same indications may not necessarily apply to this patient population because the T cells are not affected by a virus as in HIV...
November 2016: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/27930389/therapy-related-myeloid-neoplasms
#7
Arnold Ganser, Michael Heuser
PURPOSE OF REVIEW: Advances in the genetic characterization of patients with therapy-related myeloid neoplasms (t-MNs) have changed our understanding of the pathogenesis of these diseases. In addition, extensive sequencing studies have identified recurrent mutations with diagnostic and prognostic impact. Thus, the revised version of the WHO classification combines therapy-related myelodysplastic syndromes (t-MDS) and therapy-related acute myeloid leukemia (t-AML) in the one entity of t-MNs because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis...
December 7, 2016: Current Opinion in Hematology
https://www.readbyqxmd.com/read/27928093/imported-disease-screening-prior-to-chemotherapy-and-bone-marrow-transplantation-for-oncohematological-malignancies
#8
Adrián Sánchez-Montalvá, Fernando Salvador, Isabel Ruiz-Camps, Pere Barba, David Valcárcel, Elena Sulleiro, Enrique Sanz-García, Israel Molina
Reactivation of latent imported infections has been periodically reported in migrant patients undergoing immunosuppression. We performed a prospective study at Vall d'Hebron University Hospital (Barcelona, Spain). Migrant patients over 16 years with the diagnosis of any oncohematologic disease were included. Patients were tested for soil-transmitted helminths, hepatitis virus, and human immunodeficiency virus, Treponema pallidum, human T-cell lymphotropic virus, latent tuberculosis infection, Toxoplasma spp...
December 7, 2016: American Journal of Tropical Medicine and Hygiene
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
#9
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/27923824/human-dendritic-cells-mitigate-nk-cell-dysfunction-mediated-by-nonselective-jak1-2-blockade
#10
Shane A Curran, Justin A Shyer, Erin T St Angelo, Lillian R Talbot, Sneh Sharma, David J Chung, Glenn Heller, Katharine C Hsu, Brian C Betts, James W Young
Janus kinase (JAK) inhibitors have achieved positive responses in myeloproliferative neoplasms, but at the expense of decreased natural killer (NK) cell numbers and compromised function. Selective JAK2 inhibition may also have a role in preventing and treating graft-vs-host disease after allogeneic hematopoietic stem cell transplantation. Although JAK inhibitors can impair monocyte-derived dendritic cell (moDC) activation and function and suppress effector T-cell responses, the effects on NK cells and the relevant mechanisms remain undefined...
6, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27917176/graft-immune-cell-composition-associates-with-clinical-outcome-of-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-aml
#11
Ulla Impola, Antti Larjo, Urpu Salmenniemi, Mervi Putkonen, Maija Itälä-Remes, Jukka Partanen
Complications of allogeneic hematopoietic stem cell transplantation (HSCT) have been attributed to immune cells transferred into the patient with the graft. However, a detailed immune cell composition of the graft is usually not evaluated. In the present study, we determined the level of variation in the composition of immune cells between clinical HSCT grafts and whether this variation is associated with clinical outcome. Sizes of major immune cell populations in 50 clinical grafts from a single HSCT Centre were analyzed using flow cytometry...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27916847/aortic-root-dilatation-in-mucopolysaccharidosis-i-vii
#12
Meena Bolourchi, Pierangelo Renella, Raymond Y Wang
The prevalence of aortic root dilatation (ARD) in mucopolysaccharidosis (MPS) is not well documented. We investigated aortic root measurements in 34 MPS patients at the Children's Hospital of Orange County (CHOC). The diagnosis, treatment status, age, gender, height, weight and aortic root parameters (aortic valve annulus (AVA), sinuses of Valsalva (SoV), and sinotubular junction (STJ)) were extracted by retrospective chart review and echocardiographic measurements. Descriptive statistics, ANOVA, and paired post-hoc t-tests were used to summarize the aortic dimensions...
November 29, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27914462/recombinant-mhc-tetramers-for-isolation-of-virus-specific-cd8-cells-from-healthy-donors-potential-approach-for-cell-therapy-of-posttransplant-cytomegalovirus-infection
#13
A S Vdovin, S Y Filkin, P R Yefimova, S A Sheetikov, N M Kapranov, Y O Davydova, E S Egorov, E G Khamaganova, M Y Drokov, L A Kuzmina, E N Parovichnikova, G A Efimov, V G Savchenko
Patients undergoing allogeneic hematopoietic stem cell transplantation have a high risk of cytomegalovirus reactivation, which in the absence of T-cell immunity can result in the development of an acute inflammatory reaction and damage of internal organs. Transfusion of the virus-specific donor T-lymphocytes represents an alternative to a highly toxic and often ineffective antiviral therapy. Potentially promising cell therapy approach comprises transfusion of cytotoxic T-lymphocytes, specific to the viral antigens, immediately after their isolation from the donor's blood circulation without any in vitro expansion...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27913602/clonal-conversion-of-b-lymphoid-leukemia-reveals-cross-lineage-transfer-of-malignant-states
#14
Rajesh Somasundaram, Josefine Åhsberg, Kazuki Okuyama, Jonas Ungerbäck, Henrik Lilljebjörn, Thoas Fioretos, Tobias Strid, Mikael Sigvardsson
Even though leukemia is considered to be confined to one specific hematopoietic cell type, cases of acute leukemia of ambiguous lineage and patients relapsing in phenotypically altered disease suggest that a malignant state may be transferred between lineages. Because B-cell leukemia is associated with mutations in transcription factors of importance for stable preservation of lineage identity, we here investigated the potential lineage plasticity of leukemic cells. We report that primary pro-B leukemia cells from mice carrying heterozygous mutations in either or both the Pax5 and Ebf1 genes, commonly mutated in human leukemia, can be converted into T lineage leukemia cells...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27913524/cellular-and-vaccine-immunotherapy-for-multiple-myeloma
#15
Alfred L Garfall, Edward A Stadtmauer
Allogeneic hematopoietic cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies and vaccines seek to induce more specific, reliable, and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Advances in molecular biology, and basic and applied immunology, have led to promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes, vaccine primed ex vivo expanded autologous T cells, expanded marrow-infiltrating lymphocytes, and plasma cell/dendritic cell fusion vaccines...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913458/therapy-related-myeloid-neoplasms-does-knowing-the-origin-help-to-guide-treatment
#16
Michael Heuser
Therapy-related myeloid neoplasms (t-MN) combine t-MDS and therapy related acute myeloid leukemia (t-AML) patients in one entity because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis. Treatment with epipodophyllotoxins like etoposide has been associated with a short interval between treatment and development of t-AML, with fusion oncogenes like KMT2A/MLL-MLLT3 and a better prognosis. In contrast, treatment with alkylating agents has been associated with a longer latency, an initial MDS phase, adverse cytogenetics, and a poor prognosis...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27909435/immune-reconstitution-after-allogeneic-hematopoietic-stem-cell-transplantation
#17
REVIEW
Justyna Ogonek, Mateja Kralj Juric, Sakhila Ghimire, Pavankumar Reddy Varanasi, Ernst Holler, Hildegard Greinix, Eva Weissinger
The timely reconstitution and regain of function of a donor-derived immune system is of utmost importance for the recovery and long-term survival of patients after allogeneic hematopoietic stem cell transplantation (HSCT). Of note, new developments such as umbilical cord blood or haploidentical grafts were associated with prolonged immunodeficiency due to delayed immune reconstitution, raising the need for better understanding and enhancing the process of immune reconstitution and finding strategies to further optimize these transplant procedures...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27907031/in-vitro-pre-clinical-validation-of-suicide-gene-modified-anti-cd33-redirected-chimeric-antigen-receptor-t-cells-for-acute-myeloid-leukemia
#18
Kentaro Minagawa, Muhammad O Jamil, Mustafa Al-Obaidi, Larisa Pereboeva, Donna Salzman, Harry P Erba, Lawrence S Lamb, Ravi Bhatia, Shin Mineishi, Antonio Di Stasi
BACKGROUND: Approximately fifty percent of patients with acute myeloid leukemia can be cured with current therapeutic strategies which include, standard dose chemotherapy for patients at standard risk of relapse as assessed by cytogenetic and molecular analysis, or high-dose chemotherapy with allogeneic hematopoietic stem cell transplant for high-risk patients. Despite allogeneic hematopoietic stem cell transplant about 25% of patients still succumb to disease relapse, therefore, novel strategies are needed to improve the outcome of patients with acute myeloid leukemia...
2016: PloS One
https://www.readbyqxmd.com/read/27906865/management-of-post-transplant-lymphoproliferative-disorders
#19
Gabriela Llaurador, Lauren McLaughlin, Birte Wistinghausen
PURPOSE OF REVIEW: Post-transplant lymphoproliferative disease (PTLD) is a major complication of hematopoietic stem cell and solid organ transplantation. The incidence of transplantation in childhood has been steadily rising, making PTLD the most common form of lymphoproliferation in childhood. The purpose of this review is to summarize the role of the Epstein-Barr virus (EBV) in the pathophysiology and discuss the management of PTLD. RECENT FINDINGS: More than 90% of pediatric PTLD is EBV-positive...
November 30, 2016: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/27906171/combined-nifuroxazide-and-sat05f-therapy-reduces-graft-versus-host-disease-after-experimental-allogeneic-bone-marrow-transplantation
#20
Huijie Jia, Tiesuo Zhao, Yinghua Ji, Xiaolong Jia, Wenjing Ren, Chen Li, Minming Li, Yali Xiao, Hui Wang, Kailin Xu
Acute graft-versus-host disease (aGvHD) is the major barrier to the broader use of allogenetic hematopoietic stem cells. However, currently these are no highly specific and efficient drugs. Monotherapy is not sufficient and more efficient and safe therapeutic regimen are urgent need. Studies demonstrated TLR9 and Stat3 signal pathways are critical for antigen-presenting cell maturation and T-cell activation, which are important mediators in aGvHD. Specific block these two critical signal pathways using their inhibitors SAT05f and nifuroxazide may be the novel strategies for aGvHD therapy...
December 1, 2016: Cell Death & Disease
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