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https://www.readbyqxmd.com/read/28729337/raising-the-bar-for-chronic-gvhd-trials
#1
Nicolaus Kröger
No abstract text is available yet for this article.
July 20, 2017: Blood
https://www.readbyqxmd.com/read/28729148/clinical-grade-expanded-tregs-prevent-gvhd-while-allowing-a-powerful-t-cell-dependent-gvl-effect-in-murine-models
#2
B Del Papa, L Ruggeri, E Urbani, S Baldoni, D Cecchini, T Zei, R Iacucci Ostini, B Crescenzi, A Carotti, A Pierini, P Sportoletti, P Di Bartolomeo, F Falzetti, C Mecucci, A Velardi, M F Martelli, M Di Ianni
We developed a GMP-compatible expansion protocol, to improve number and purity of Tregs available for clinical trials. Six clinical grade separation procedures were performed, followed by expansion with high-dose interleukin (IL)-2, anti-CD3/anti-CD28 TCR stimulation and rapamycin for 19 days achieving a median of 8.5 fold (6.25-13.7) expansion. FOXP3 expression was stably maintained over the culture period, while the percentage of CD127 was significantly reduced. The in vitro suppression assay showed a strong MLR inhibition...
July 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28729147/adult-umbilical-cord-blood-transplantation-using-myeloablative-thiotepa-total-body-irradiation-and-fludarabine-conditioning
#3
Sarah Anand, Samantha Thomas, Kelly Corbet, Cristina Gasparetto, Gwynn D Long, Richard Lopez, Ashley K Morris, David A Rizzieri, Keith M Sullivan, Anthony D Sung, Stefanie Sarantopoulos, Nelson J Chao, Mitchell E Horwitz
Treatment related mortality (TRM) remains elevated in adult patients undergoing umbilical cord blood (UCB) transplantation, including an early rise in TRM suggestive of excessive toxicity associated with the standard myeloablative total body irradiation (TBI), fludarabine, and cyclophosphamide regimen. In an attempt to reduce regimen-related toxicity, we previously studied a modified myeloablative regimen with total body irradiation (1350 cGy) and fludarabine (160 mg/m(2)); TRM was decreased but neutrophil engraftment was suboptimal...
July 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28725044/cord-blood-nk-cells-engineered-to-express-il-15-and-a-cd19-targeted-car-show-long-term-persistence-and-potent-anti-tumor-activity
#4
E Liu, Y Tong, G Dotti, H Shaim, B Savoldo, M Mukherjee, J Orange, X Wan, X Lu, A Reynolds, M Gagea, P Banerjee, R Cai, M H Bdaiwi, R Basar, M Muftuoglu, L Li, D Marin, W Wierda, M Keating, R Champlin, E Shpall, K Rezvani
Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T-cells against leukemia and lymphoma with promising clinical results.(1-3) Extending this approach to allogeneic T-cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy...
July 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28724800/siglec-g-represses-damp-mediated-effects-on-t-cells
#5
Tomomi Toubai, Corinne Rossi, Katherine Oravecz-Wilson, Cynthia Zajac, Chen Liu, Thomas Braun, Hideaki Fujiwara, Julia Wu, Yaping Sun, Stuart Brabbs, Hiroya Tamaki, John Magenau, Pang Zheng, Yang Liu, Pavan Reddy
The role of negative regulators or suppressors of the damage-associated molecular pattern-mediated (DAMP-mediated) stimulation of innate immune responses is being increasingly appreciated. However, the presence and function of suppressors of DAMP-mediated effects on T cells, and whether they can be targeted to mitigate T cell-dependent immunopathology remain unknown. Sialic acid-binding immunoglobulin-like lectin G (Siglec-G) is a negative regulator of DAMP-mediated responses in innate immune cells, but its T cell-autonomous role is unknown...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28724796/host-interleukin-6-production-regulates-inflammation-but-not-tryptophan-metabolism-in-the-brain-during-murine-gvhd
#6
Ludovic Belle, Vivian Zhou, Kara L Stuhr, Margaret Beatka, Emily M Siebers, Jennifer M Knight, Michael W Lawlor, Casey Weaver, Misato Hashizume, Cecilia J Hillard, William R Drobyski
Graft-versus-host disease (GVHD) induces pathological damage in peripheral target organs leading to well-characterized, organ-specific clinical manifestations. Patients with GVHD, however, can also have behavioral alterations that affect overall cognitive function, but the extent to which GVHD alters inflammatory and biochemical pathways in the brain remain poorly understood. In the current study, we employed complementary murine GVHD models to demonstrate that alloreactive donor T cells accumulate in the brain and affect a proinflammatory cytokine milieu that is associated with specific behavioral abnormalities...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28721499/treg-protected-donor-lymphocyte-infusions-a-new-tool-to-address-the-graft-versus-leukemia-effect-in-the-absence-of-graft-versus-host-disease-in-patients-relapsed-after-hsct
#7
Mauro Di Ianni, Paola Olioso, Raffaella Giancola, Stella Santarone, Annalisa Natale, Gabriele Papalinetti, Ida Villanova, Stefano Baldoni, Ambra Di Tommaso, Tiziana Bonfini, Patrizia Accorsi, Paolo Di Bartolomeo
In high-risk acute leukemia patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT), adoptive immunotherapy with T regulatory cells (Tregs) and T conventional cells (Tcons) prevented acute and chronic graft-versus-host disease (GvHD), favored post-transplant immunological reconstitution and was associated with a powerful graft-versus-leukemia (GvL) effect. With a particularly innovative approach, we developed a treatment with a Treg-protected donor lymphocyte infusion (DLI) for patients with early relapse after HSCT and we report here the results obtained in the first patient with APL (M3v) relapsed after a second matched allogeneic HSCT (15% blasts and 75% of donor cells in bone marrow)...
July 18, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28716402/the-role-of-low-dose-anti-thymocyte-globulin-as-standard-prophylaxis-in-mismatched-and-matched-unrelated-hematopoietic-peripheral-stem-cell-transplantation-for-hematologic-malignancies
#8
Ioanna Sakellari, Ioannis Batsis, Zoi Bousiou, Despina Mallouri, Varnavas Constantinou, Eleni Gavriilaki, Christos Smias, Evangelia Yannaki, Panayotis Kaloyannidis, Giorgos Papaioannou, Niki Stavroyianni, Antonia Syrigou, Damianos Sotiropoulos, Asimina Fylaktou, Aliki Tsompanakou, Riad Saloum, Achilles Anagnostopoulos
INTRODUCTION: Anti-thymocyte globulin (ATG)-based immunosuppressive therapy is often used in allogeneic hematopoietic cell transplantation to reduce incidence and severity of graft-versus-host disease (GVHD). PATIENTS AND METHODS: In our observational study, ATG (rabbit, Thymoglobulin; Sanofi, 5 mg/kg) was administered as a standardized part of the conditioning in 97 patients with a median age of 34 years (range, 14-58 years), allotransplanted for hematologic malignancies from matched (8/8; n = 52) and allele or antigen mismatched (7/8; n = 43 and 6/8; n = 2) unrelated donors...
June 29, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28714944/impact-of-the-presence-of-hla-1-locus-mismatch-and-the-use-of-low-dose-antithymocyte-globulin-in-unrelated-bone-marrow-transplantation
#9
K Kawamura, J Kanda, S Fuji, M Murata, K Ikegame, K Yoshioka, T Fukuda, Y Ozawa, N Uchida, K Iwato, T Sakura, M Hidaka, H Hashimoto, T Ichinohe, Y Atsuta, Y Kanda
HLA 1-locus-mismatched unrelated donors (1MMUD) have been used in allogeneic hematopoietic stem cell transplantation (allo-HCT) for patients who lack an HLA-matched donor. We retrospectively analyzed 3313 patients with acute leukemia or myelodysplastic syndrome who underwent bone marrow transplantation from an HLA allele-matched unrelated donor (MUD) or 1MMUD between 2009 and 2014. We compared the outcomes of MUD (n=2089) and 1MMUD with antithymocyte globulin (ATG) (1MM-ATG(+); n=109) with those of 1MMUD without ATG (1MM-ATG(-); n=1115)...
July 17, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28713380/targeting-the-human-t-cell-inducible-costimulator-molecule-with-a-monoclonal-antibody-prevents-graft-vs-host-disease-and-preserves-graft-vs-leukemia-in-a-xenograft-murine-model
#10
Aude Burlion, Simon Brunel, Nicolas Y Petit, Daniel Olive, Gilles Marodon
BACKGROUND: Graft-vs-host disease (GVHD) is a major complication of allogenic bone marrow transplantation (BMT). Targeting costimulatory molecules with antagonist antibodies could dampen the excessive immune response that occurs, while preserving the beneficial graft vs leukemia (GVL) of the allogeneic response. Previous studies using a mouse model of GVHD have shown that targeting the T-cell Inducible COStimulator (ICOS, CD278) molecule is beneficial, but it is unclear whether the same applies to human cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28712935/phase-ii-study-of-sequential-infusion-of-dli-and-cytokine-induced-killer-cells-for-patients-relapsed-after-allohsct
#11
Martino Introna, Federico Lussana, Alessandra Algarotti, Elisa Gotti, Rut Valgarsdottir, Caterina Micò, Anna Grassi, Chiara Pavoni, Maria Luisa Ferrari, Federica Delaini, Elisabetta Todisco, Irene Cavattoni, Sara Deola, Ettore Biagi, Adriana Balduzzi, Attilio Rovelli, Matteo Parma, Sara Napolitano, Giusy Sgroi, Emanuela Marrocco, Paolo Perseghin, Daniela Belotti, Benedetta Cabiati, Giuseppe Gaipa, Josée Golay, Andrea Biondi, Alessandro Rambaldi
Seventy-four patients relapsed after allogeneic stem cell transplantation were enrolled in a phase IIA study and treated with the sequential infusion of donor lymphocytes (DLI) followed by cytokine induced killer (CIK) cells. Seventy-three patients were available for the intention to treat analysis. At least one infusion of CIK cells was given to 59 patients, while 43 patients received the complete cell therapy planned (58%). Overall, 12 patients (16%) developed acute GvHD (aGvHD, of grade I-II in 7 cases and grade III-IV in 5)...
July 13, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28712934/donor-lymphocyte-infusions-used-to-treat-mixed-chimeric-and-high-risk-patient-populations-in-the-relapsed-and-non-relapsed-settings-after-allogeneic-transplant-for-hematologic-malignancies-are-associated-with-high-5-year-survival-if-persistent-full-donor-chimerism
#12
Lauren E Caldemeyer, Luke P Akard, John R Edwards, Anand Tandra, Dawn R Wagenknecht, Michael J Dugan
Mixed chimerism (MC), a persistent or increasing number of host cells after allogeneic hematopoietic stem cell transplant (HSCT), is a predictor of disease relapse. Donor lymphocyte infusions (DLI) have the potential to enhance the graft vs. malignancy (GvM) effect, reducing the risk of relapse in patients with MC. Hence, in addition to utilizing DLI in the relapsed setting, there is a motivation to pursue pre-emptive DLI for patients in complete remissions (CR) after HSCT. To assess the safety and efficacy of DLI, records of 86 patients who received DLI between 2003 and 2015 at a single institution were studied retrospectively...
July 13, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28712863/harnessing-the-cd1-restricted-t-cell-response-for-leukemia-adoptive-immunotherapy
#13
Michela Consonni, Claudia de Lalla, Alessandra Bigi, Paolo Dellabona, Giulia Casorati
Disease recurrence following chemotherapy and allogeneic hematopoietic cell transplantation is the major unmet clinical need of acute leukemia. Adoptive cell therapy (ACT) with allogeneic T lymphocytes can control recurrences at the cost of inducing detrimental GVHD. Targeting T cell recognition on leukemia cells is therefore needed to overcome the problem and ensure safe and durable disease remission. In this review, we discuss adoptive cells therapy based on CD1-restricted T cells specific for tumor associated self-lipid antigens...
July 8, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28711728/allogeneic-blood-or-marrow-transplantation-with-post-transplantation-cyclophosphamide-as-graft-versus-host-disease-prophylaxis-in-multiple-myeloma
#14
Nilanjan Ghosh, Xiaobu Ye, Hua-Ling Tsai, Javier Bolaños-Meade, Ephraim J Fuchs, Leo Luznik, Lode J Swinnen, Douglas E Gladstone, Richard F Ambinder, Ravi Varadhan, Satish Shanbhag, Robert A Brodsky, Ivan M Borrello, Richard J Jones, William Matsui, Carol Ann Huff
Allogeneic blood or marrow transplantation (alloBMT) may lead to long-term disease control in patients with multiple myeloma (MM). However, historically, the use of alloBMT in MM has been limited by its high non-relapse mortality (NRM) rates primarily from graft versus host disease (GVHD). We previously demonstrated that post-transplantation cyclophosphamide (PTCy) decreases the toxicities of both acute and chronic GVHD rates following alloBMT. Here we examine the impact of PTCy in MM patients undergoing alloBMT at Johns Hopkins Hospital...
July 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28711727/a-chemotherapy-only-regimen-of-busulfan-melphalan-and-fludarabine-and-rabbit-atg-followed-by-allogeneic-t-cell-depleted-hematopoietic-stem-cell-transplants-for-the-treatment-of-myeloid-malignancies
#15
Barbara Spitzer, Ann A Jakubowski, Esperanza B Papadopoulos, Kirsten Fuller, Patrick D Hilden, James W Young, Juliet Barker, Guenther Koehne, Miguel-Angel Perales, Katharine C Hsu, Marcel R M van den Brink, Nancy A Kernan, Susan E Prockop, Andromachi Scaradavou, Hugo Castro-Malaspina, Richard J O'Reilly, Farid Boulad
We sought to develop a myeloablative chemotherapeutic regimen to secure consistent engraftment of T-cell depleted (TCD) hematopoietic stem cell transplants (HSCT) without the need for total body irradiation, thereby reducing toxicity, while maintaining low rates of GvHD and without increasing relapse. We investigated the myeloablative combination of busulfan and melphalan, with the immunosuppressive agents fludarabine and rabbit anti-thymocyte gloubin (r-ATG) as cytoreduction prior to a T-cell depleted HSCT...
July 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28711168/surgical-treatment-of-intestinal-complications-of-graft-versus-host-disease-in-the-pediatric-population-case-series-and-review-of-literature
#16
REVIEW
Camille A Gutierrez, Mehul V Raval, Hannah R Vester, Sonali Chaudhury, Daniel von Allmen, David H Rothstein
BACKGROUND/PURPOSE: Intestinal complications of acute graft-versus-host disease (aGVHD) include hemorrhage and perforation in the short-term, and stricture with bowel obstruction in the long-term. As medical management of severe aGVHD has improved, more patients are surviving even advanced stages of intestinal aGVHD. This review summarizes the available pediatric literature on surgical treatment of complications of intestinal GVHD. METHODS: A systematic review was performed using PubMed, Cochrane, Embase, and Scopus databases...
June 28, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28710648/clinical-associated-characteristics-and-microbiological-features-of-bloodstream-nontyphoidal-salmonella-infection-in-adult-patients-receiving-allogeneic-hematopoietic-stem-cell-transplantation
#17
Po-Shen Ko, Yao-Chung Liu, Hao-Yuan Wang, Chia-Yun Wu, Nai-Wen Fan, Chia-Jen Liu, Yuan-Bin Yu, Liang-Tsai Hsiao, Tzeon-Jye Chiou, Cheng-Hwai Tzeng, Jin-Hwang Liu, Jyh-Pyng Gau
Bloodstream nontyphoidal salmonella (NTS) infection is rare, but its associated characteristics and microbiological features in immunocompromised patients are worth paying attention to, particularly for those receiving allogeneic hematopoietic stem cell transplantation (SCT). No studies so far have analyzed post-transplant bloodstream NTS infection. Therefore, we reviewed 423 adult patients undergoing allogeneic hematopoietic SCT from 2003 to 2014. Nine out of four hundred twenty-three patients (2.13%) developed post-transplant bloodstream NTS infection, including two patients who had subsequent or combined metastatic infections...
July 15, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28706856/disseminated-nocardia-cyriacigeorgia-causing-pancreatitis-in-a-haploidentical-stem-cell-transplant-recipient
#18
Jason Chen, Jonathan Pan, Joanne Filicko-O'Hara, Margaret Kasner, Phyllis Flomenberg
We report the first published case of acute pancreatitis secondary to disseminated nocardiosis in a hematopoietic stem cell transplant (HSCT) recipient on chronic immunosuppression for graft-versus-host disease (GVHD). Nocardiosis in the HSCT population is relatively rare, and has not yet been described in haploidentical HSCT recipients. Our patient is a 28-year-old male with a history of haploidentical HSCT and GVHD of the skin and lung who was admitted to the hospital with acute pancreatitis. The workup for the etiology of his pancreatitis was initially unrevealing...
2017: IDCases
https://www.readbyqxmd.com/read/28705839/circulating-dsdna-endothelial-injury-and-complement-activation-in-thrombotic-microangiopathy-and-gvhd
#19
Nicholas J Gloude, Pooja Khandelwal, Nathan Luebbering, Dana T Lounder, Sonata Jodele, Matthew N Alder, Adam Lane, Alyss Wilkey, Kelly E Lake, Bridget Litts, Stella M Davies
TA-TMA is a common and poorly recognized complication of HSCT associated with excessive complement activation, likely triggered by endothelial injury. An important missing piece is the link between endothelial injury and complement activation. We hypothesized that neutrophil extracellular traps (NETs) mechanistically link endothelial damage with complement activation and subsequent TA-TMA. Neutrophil activation releases granule proteins together with double stranded DNA (dsDNA), to form extracellular fibers known as NETs...
July 13, 2017: Blood
https://www.readbyqxmd.com/read/28705454/efficacy-of-two-different-doses-of-rabbit-anti-t-lymphocyte-globulin-to-prevent-graft-versus-host-disease-in-children-with-haematological-malignancies-transplanted-from-an-unrelated-donor-a-multicentre-randomised-open-label-phase-3-trial
#20
Franco Locatelli, Maria Ester Bernardo, Alice Bertaina, Carla Rognoni, Patrizia Comoli, Attilio Rovelli, Andrea Pession, Franca Fagioli, Claudio Favre, Edoardo Lanino, Giovanna Giorgiani, Pietro Merli, Daria Pagliara, Arcangelo Prete, Marco Zecca
BACKGROUND: Although rabbit anti-T-lymphocyte globulin (ATLG) is largely used for the prevention of immune-mediated complications in patients given allogeneic haemopoietic stem-cell transplantation (HSCT) from an unrelated donor, the optimum dose of this drug in children is still undefined. We aimed to test whether a higher dose of ATLG was superior to a lower dose for prevention of grade II-IV acute graft-versus-host disease (GVHD). METHODS: We conducted a multicentre, randomised, open-label, phase 3 trial in seven Italian centres comparing two different doses of ATLG (30 mg/kg vs 15 mg/kg, given intravenously over 3 days, from day -4 to -2) in children (aged 0-18 years) with haematological malignancies transplanted from an unrelated donor, selected using high-resolution typing for HLA-class I/II loci...
July 10, 2017: Lancet Oncology
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