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https://www.readbyqxmd.com/read/28187014/delayed-donor-bone-marrow-infusion-induces-liver-transplant-tolerance
#1
Yan Xie, Yang Wu, Kang Xin, Jiao-Jing Wang, Hong Xu, Suzanne T Ildstad, Joseph Leventhal, Guang-Yu Yang, Zheng Zhang, Josh Levitsky
BACKGROUND: Nonmyeloablative conditioning followed by donor bone marrow infusion (BMI) to induce tolerance has not been robustly tested in liver transplantation (LT) and may be unsafe at the time of LT. We hypothesized T cell depleted BMI is effective in inducing tolerance when delayed after LT, resulting in potentially safer future clinical applications. METHODS: Nonimmunosuppressed syngeneic (Lewis to Lewis) and allogeneic (ACI to Lewis) rat LT transplants were initially performed as controls...
February 10, 2017: Transplantation
https://www.readbyqxmd.com/read/28093487/a-pilot-trial-of-the-combination-of-vemurafenib-with-adoptive-cell-therapy-in-patients-with-metastatic-melanoma
#2
Drew C Deniger, Mei Li M Kwong, Anna Pasetto, Mark E Dudley, John R Wunderlich, Michelle M Langhan, Chyi-Chia Richard Lee, Steven A Rosenberg
PURPOSE: This pilot feasibility clinical trial evaluated the coadministration of vemurafenib, a small-molecule antagonist of BRAF(V600) mutations, and tumor-infiltrating lymphocytes (TIL) for the treatment of metastatic melanoma. EXPERIMENTAL DESIGN: A metastatic tumor was resected for growth of TILs, and patients were treated with vemurafenib for 2 weeks, followed by resection of a second lesion. Patients then received a nonmyeloablative preconditioning regimen, infusion of autologous TILs, and high-dose interleukin-2 administration...
January 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28087884/the-role-of-immunoglobulin-prophylaxis-for-prevention-of-cytomegalovirus-infection-in-pediatric-hematopoietic-stem-cell-transplantation-recipients
#3
Gal Goldstein, Tal Frenkel Rutenberg, Sarina Levy Mendelovich, Daphna Hutt, Michal Teperberg Oikawa, Amos Toren, Bella Bielorai
BACKGROUND: Following cessation of intravenous immunoglobulin (IVIg) administration for allogeneic hematopoietic stem cell transplantation (HSCT) recipients at our unit, we observed a sharp decline in the incidence of cytomegalovirus (CMV) infection. PROCEDURE: We conducted a retrospective study of the role of IVIg in the prevention of CMV infection in children and young adults who underwent HSCT from matched related donor. RESULTS: We included 109 patients (IVIg+/IVIg- ratio 82/27)...
January 14, 2017: 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
#4
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/27982315/haploidentical-transplantation-of-hematopoietic-stem-cells
#5
Nelson Hamerschlak
OBJECTIVE: To review and discuss the literature on hematopoietic stem cell transplantation (HSCT) with haploidentical donors in Brazil. METHOD: Literature review. RESULTS: The haploidentical hematopoietic stem cell transplantations have become a safe option in hematology since the 80s, with the possibility of ex-vivo T-cell depletion. However, its broad use worldwide occurred with the advent of haploidentical nonmyeloablative transplants using in vivo T-cell depletion with the administration of post-transplant cyclophosphamide...
October 2016: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/27934766/depleting-dietary-valine-permits-nonmyeloablative-mouse-hematopoietic-stem-cell-transplantation
#6
Yuki Taya, Yasunori Ota, Adam C Wilkinson, Ayano Kanazawa, Hiroshi Watarai, Masataka Kasai, Hiromitsu Nakauchi, Satoshi Yamazaki
A specialized bone marrow microenvironment (niche) regulates hematopoietic stem cell (HSC) self-renewal and commitment. For successful donor-HSC engraftment, the niche must be emptied via myeloablative irradiation or chemotherapy. However, myeloablation can cause severe complications and even mortality. Here we report that the essential amino acid valine is indispensable for the proliferation and maintenance of HSCs. Both mouse and human HSCs failed to proliferate when cultured in valine-depleted conditions...
December 2, 2016: Science
https://www.readbyqxmd.com/read/27934561/various-regimens-of-total-body-irradiation-for-hematopoietic-stem-cell-transplant
#7
Naoya Ishibashi, Toshiya Maebayashi, Takuya Aizawa, Masakuni Sakaguchi, Osamu Abe, Kazuyoshi Sakanishi, Yuji Endoh, Tsutomu Saito, Jiro Kawamori, Yoshiaki Tanaka
OBJECTIVES: We aimed to evaluate the safety of total body irradiation before bone marrow transplant. MATERIALS AND METHODS: We analyzed 110 patients (65 male, 45 female) who underwent total body irradiation for hematopoietic stem cell transplant between May 1998 and March 2013. Median age at total body irradiation was 17 years (range, 1-62 y). Median observation time was 777 days (range, 31-5494 d). Initial diagnoses were acute lymphoblastic leukemia (24 patients), acute myeloid leukemia (26 patients), chronic myeloid leukemia (7 patients), myelodysplastic syndrome (8 patients), malignant lymphoma (13 patients), mucopolysaccharidosis (12 patients), neuroblastoma (10 patients), and other diseases (10 patients)...
December 2016: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/27888014/nonmyeloablative-haploidentical-bone-marrow-transplantation-with-post-transplantation-cyclophosphamide-for-pediatric-and-young-adult-patients-with-high-risk-hematologic-malignancies
#8
Orly R Klein, Jessica Buddenbaum, Noah Tucker, Allen R Chen, Christopher J Gamper, David Loeb, Elias Zambidis, Nicolas J Llosa, Jeffrey S Huo, Nancy Robey, Mary Jo Holuba, Yvette L Kasamon, Shannon R McCurdy, Richard Ambinder, Javier Bolaños-Meade, Leo Luznik, Ephraim J Fuchs, Richard J Jones, Kenneth R Cooke, Heather J Symons
Lower-intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious for adult patients with hematologic malignancies. We report data for pediatric/young adult patients with high-risk hematologic malignancies (n = 40) treated with nonmyeloablative haploidentical BMT with post-transplantation cyclophosphamide from 2003 to 2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplantation immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus...
February 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27872868/minor-antigen-disparities-impede-induction-of-long-lasting-chimerism-and-tolerance-through-bone-marrow-transplantation-with-costimulation-blockade
#9
Sinda Bigenzahn, Ines Pree, Christoph Klaus, Nina Pilat, Benedikt Mahr, Elisabeth Schwaiger, Patrick Nierlich, Friedrich Wrba, Thomas Wekerle
Mixed chimerism and tolerance can be successfully induced in rodents through allogeneic bone marrow transplantation (BMT) with costimulation blockade (CB), but varying success rates have been reported with distinct models and protocols. We therefore investigated the impact of minor antigen disparities on the induction of mixed chimerism and tolerance. C57BL/6 (H2(b)) mice received nonmyeloablative total body irradiation (3 Gy), costimulation blockade (anti-CD40L mAb and CTLA4Ig), and 2 × 10(7) bone marrow cells (BMC) from either of three donor strains: Balb/c (H2(d)) (MHC plus multiple minor histocompatibility antigen (mHAg) mismatched), B10...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27861294/induction-of-major-histocompatibility-complex-mismatched-mouse-lung-allograft-acceptance-with-combined-donor-bone-marrow-lung-transplant-using-a-12-hour-nonmyeloablative-conditioning-regimen
#10
Jeffrey M Dodd-O, Sudipto Ganguly, Ante Vulic, Angela Panoskaltsis-Mortari, John F McDyer, Leo Luznik
BACKGROUND: Despite broad and intense conventional immunosuppression, long-term survival after lung transplantation lags behind that for other solid organ transplants, primarily because of allograft rejection. Therefore, new strategies to promote lung allograft acceptance are urgently needed. The purpose of the present study was to induce allograft tolerance with a protocol compatible with deceased donor organ utilization. METHODS: Using the major histocompatibility complex-mismatched mouse orthotopic lung transplant model, we investigated a conditioning regimen consisting of pretransplant T cell depletion, low-dose total body irradiation and posttransplant (donor) bone marrow, and splenocyte infusion followed by posttransplantation cyclophosphamide...
December 2016: Transplantation
https://www.readbyqxmd.com/read/27846611/comparable-composite-endpoints-after-hla-matched-and-hla-haploidentical-transplantation-with-post-transplantation-cyclophosphamide
#11
Shannon R McCurdy, Yvette L Kasamon, Christopher G Kanakry, Javier Bolaños-Meade, Hua-Ling Tsai, Margaret M Showel, Jennifer A Kanakry, Heather J Symons, Ivana Gojo, B Douglas Smith, Maria P Bettinotti, William H Matsui, Amy E Dezern, Carol Ann Huff, Ivan Borrello, Keith W Pratz, Douglas E Gladstone, Lode J Swinnen, Robert A Brodsky, Mark J Levis, Richard F Ambinder, Ephraim J Fuchs, Gary L Rosner, Richard J Jones, Leo Luznik
Composite endpoints that not only encompass mortality and relapse, but other critical post-transplant events such as graft-versus-host disease, are being increasingly utilized to quantify survival without significant morbidity after allogeneic blood or marrow transplantation. High-dose, post-transplantation cyclophosphamide reduces severe graft-versus-host disease with allogeneic marrow transplantation, making composite endpoints after this management particularly interesting. We retrospectively analyzed 684 adults with hematologic malignancies who received T-cell-replete bone marrow grafts and cyclophosphamide after myeloablative HLA-matched related (n=192) or unrelated (n=120), or non-myeloablative HLA-haploidentical (n=372) donor transplantation...
February 2017: Haematologica
https://www.readbyqxmd.com/read/27846155/effect-of-ex-vivo-expanded-recipient-regulatory-t-cells-on-hematopoietic-chimerism-and-kidney-allograft-tolerance-across-mhc-barriers-in-cynomolgus-macaques
#12
Raimon Duran-Struuck, Hugo P Sondermeijer, Leo Bühler, Paula Alonso-Guallart, Jonah Zitsman, Yojiro Kato, Anette Wu, Alicia N McMurchy, David Woodland, Adam Griesemer, Mercedes Martinez, Svetlan Boskovic, Tatsuo Kawai, A Benedict Cosimi, Cheng-Shie Wuu, Andrea Slate, Markus Y Mapara, Sam Baker, Rafal Tokarz, Vivette DʼAgati, Scott Hammer, Marcus Pereira, W Ian Lipkin, Thomas Wekerle, Megan K Levings, Megan Sykes
BACKGROUND: Infusion of recipient regulatory T (Treg) cells promotes durable mixed hematopoietic chimerism and allograft tolerance in mice receiving allogeneic bone marrow transplant (BMT) with minimal conditioning. We applied this strategy in a Cynomolgus macaque model. METHODS: CD4 CD25 Treg cells that were polyclonally expanded in culture were highly suppressive in vitro and maintained high expression of FoxP3. Eight monkeys underwent nonmyeloablative conditioning and major histocompatibility complex mismatched BMT with or without Treg cell infusion...
February 2017: Transplantation
https://www.readbyqxmd.com/read/27816649/engraftment-efficiency-after-intra-bone-marrow-versus-intravenous-transplantation-of-bone-marrow-cells-in-a-canine-nonmyeloablative-dog-leukocyte-antigen-identical-transplantation-model
#13
Sandra Lange, Anne Steder, Doreen Killian, Gudrun Knuebel, Anett Sekora, Heike Vogel, Iris Lindner, Simone Dunkelmann, Friedrich Prall, Hugo Murua Escobar, Mathias Freund, Christian Junghanss
An intra-bone marrow (IBM) hematopoietic stem cell transplantation (HSCT) is assumed to optimize the homing process and therefore to improve engraftment as well as hematopoietic recovery compared with conventional i.v. HSCT. This study investigated the feasibility and efficacy of IBM HSCT after nonmyeloablative conditioning in an allogeneic canine HSCT model. Two study cohorts received IBM HSCT of either density gradient (IBM-I, n = 7) or buffy coat (IBM-II, n = 6) enriched bone marrow cells. An historical i...
February 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27815446/blood-stem-cell-activity-is-arrested-by-th1-mediated-injury-preventing-engraftment-following-nonmyeloablative-conditioning
#14
Antonia M S Müller, Mareike Florek, Holbrook E K Kohrt, Natascha J Küpper, Alexander Filatenkov, Jessica A Linderman, Husein Hadeiba, Robert S Negrin, Judith A Shizuru
T cells are widely used to promote engraftment of hematopoietic stem cells (HSCs) during an allogeneic hematopoietic cell transplantation. Their role in overcoming barriers to HSC engraftment is thought to be particularly critical when patients receive reduced doses of preparative chemotherapy and/or radiation compared with standard transplantations. In this study, we sought to delineate the effects CD4(+) cells on engraftment and blood formation in a model that simulates clinical hematopoietic cell transplantation by transplanting MHC-matched, minor histocompatibility-mismatched grafts composed of purified HSCs, HSCs plus bulk T cells, or HSCs plus T cell subsets into mice conditioned with low-dose irradiation...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27650329/enhanced-in-utero-allogeneic-engraftment-in-mice-after-mobilizing-fetal-hscs-by-%C3%AE-4%C3%AE-1-7-inhibition
#15
Aimee G Kim, Jesse D Vrecenak, Matthew M Boelig, Linda Eissenberg, Michael P Rettig, John S Riley, Matthew S Holt, Michael A Conner, Stavros P Loukogeorgakis, Haiying Li, John F DiPersio, Alan W Flake, William H Peranteau
In utero hematopoietic cell transplantation (IUHCT) is a novel nonmyeloablative approach that results in donor-specific tolerance and mixed allogeneic chimerism. Clinical application is limited by low levels of donor cell engraftment. Competition from endogenous hematopoietic stem cells (HSCs) for limited "space" in fetal hematopoietic organs remains a significant barrier to successful IUHCT. AMD3100, a CXCR4 inhibitor, and firategrast, an α4β1 and α4β7 integrin inhibitor (α4β1/7), have been shown to disrupt HSC retention in the postnatal hematopoietic niche...
November 17, 2016: Blood
https://www.readbyqxmd.com/read/27643868/autoimmune-hemolysis-and-immune-thrombocytopenic-purpura-after-cord-blood-transplantation-may-be-life-threatening-and-warrants-early-therapy-with-rituximab
#16
V Bhatt, L Shune, E Lauer, M Lubin, S M Devlin, A Scaradavou, R Parameswaran, M A Perales, D M Ponce, S Mantha, N A Kernan, J N Barker
Autoimmune hemolysis (AH) and immune thrombocytopenic purpura (ITP) are recognized complications after cord blood transplantation (CBT). We evaluated the incidence and characteristics of AH/ITP after double-unit CBT in a day 100 landmark analysis of 152 patients (median age 36 years, range 0.9-70 years) transplanted for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor (CNI)/mycophenolate mofetil. With a median 5.2-year (range 1.6-9.7 years) survivor follow-up, 10 patients developed autoimmune cytopenias (8 AH, 1 ITP, 1 both) at a median of 10...
December 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27446989/induced-regulatory-t-cells-in-allograft-tolerance-via-transient-mixed-chimerism
#17
Kiyohiko Hotta, Akihiro Aoyama, Tetsu Oura, Yohei Yamada, Makoto Tonsho, Kyu Ha Huh, Kento Kawai, David Schoenfeld, James S Allan, Joren C Madsen, Gilles Benichou, Rex-Neal Smith, Robert B Colvin, David H Sachs, A Benedict Cosimi, Tatsuo Kawai
Successful induction of allograft tolerance has been achieved in nonhuman primates (NHPs) and humans via induction of transient hematopoietic chimerism. Since allograft tolerance was achieved in these recipients without durable chimerism, peripheral mechanisms are postulated to play a major role. Here, we report our studies of T cell immunity in NHP recipients that achieved long-term tolerance versus those that rejected the allograft (AR). All kidney, heart, and lung transplant recipients underwent simultaneous or delayed donor bone marrow transplantation (DBMT) following conditioning with a nonmyeloablative regimen...
July 7, 2016: JCI Insight
https://www.readbyqxmd.com/read/27247754/reduced-intensity-conditioning-allogeneic-hematopoietic-cell-transplantation-for-older-patients-with-acute-myeloid-leukemia
#18
REVIEW
Gaurav Goyal, Krishna Gundabolu, Saraschandra Vallabhajosyula, Peter T Silberstein, Vijaya Raj Bhatt
Elderly patients (>60 years) with acute myeloid leukemia have a poor prognosis with a chemotherapy-alone approach. Allogeneic hematopoietic-cell transplantation (HCT) can improve overall survival (OS). However, myeloablative regimens can have unacceptably high transplant-related mortality (TRM) in an unselected group of older patients. Reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning regimens preserve the graft-versus-leukemia effects but reduce TRM. NMA regimens result in minimal cytopenia and may not require stem cell support for restoring hematopoiesis...
June 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27217459/randomized-prospective-evaluation-comparing-intensity-of-lymphodepletion-before-adoptive-transfer-of-tumor-infiltrating-lymphocytes-for-patients-with-metastatic-melanoma
#19
Stephanie L Goff, Mark E Dudley, Deborah E Citrin, Robert P Somerville, John R Wunderlich, David N Danforth, Daniel A Zlott, James C Yang, Richard M Sherry, Udai S Kammula, Christopher A Klebanoff, Marybeth S Hughes, Nicholas P Restifo, Michelle M Langhan, Thomas E Shelton, Lily Lu, Mei Li M Kwong, Sadia Ilyas, Nicholas D Klemen, Eden C Payabyab, Kathleen E Morton, Mary Ann Toomey, Seth M Steinberg, Donald E White, Steven A Rosenberg
PURPOSE: Adoptive cell transfer, the infusion of large numbers of activated autologous lymphocytes, can mediate objective tumor regression in a majority of patients with metastatic melanoma (52 of 93; 56%). Addition and intensification of total body irradiation (TBI) to the preparative lymphodepleting chemotherapy regimen in sequential trials improved objective partial and complete response (CR) rates. Here, we evaluated the importance of adding TBI to the adoptive transfer of tumor-infiltrating lymphocytes (TIL) in a randomized fashion...
July 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27165670/the-use-of-hematopoietic-stem-cells-in-autoimmune-diseases
#20
Moufida Ben Nasr, Roberto Bassi, Vera Usuelli, Alessandro Valderrama-Vasquez, Sara Tezza, Francesca D'Addio, Paolo Fiorina
Hematopoietic stem cells (HSCs) have been shown recently to hold much promise in curing autoimmune diseases. Newly diagnosed Type 1 diabetes individuals have been successfully reverted to normoglycemia by administration of autologous HSCs in association with a nonmyeloablative regimen (antithymocyte globulin + cyclophasmide). Furthermore, recent trials reported positive results by using HSCs in treatment of systemic sclerosis, multiple sclerosis and rheumatoid arthritis as well. Early data suggested that HSCs possess immunological properties that may be harnessed to alleviate the symptoms of individuals with autoimmune disorders and possibly induce remission of autoimmune diseases...
June 2016: Regenerative Medicine
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