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Lauren Veltri, Katayoun Rezvani, Betul Oran, Rohtesh Mehta, Gabriela Rondon, Partow Kebriaei, Uday Popat, Yago Nieto, Chitra Hosing, Muzaffar Qazilbash, Issa Khouri, Elizabeth Shpall, Richard Champlin, David Marin
Outcome of persons >65 years with acute myeloid leukemia (AML) is poor. A transplant from an HLA-identical sibling or an HLA-matched unrelated donor can cure some of these patients but is associated with a substantial transplant-related mortality and a high relapse risk. We analyzed 185 subjects >65 years with high-risk AML receiving conventional (n=42) or reduced-intensity (n=143) pre-transplant conditioning and a transplant from an HLA-identical sibling (n=66) or a 10/10 loci HLA-matched unrelated donor (n=119)...
October 8, 2018: Biology of Blood and Marrow Transplantation
Shaun D Mendenhall, Michael T Ginnetti, Justin D Sawyer, Steven J Verhulst, Bradford L West, L Scott Levin, Michael W Neumeister
Background: Vascularized composite allotransplantation (VCA) is an emerging and growing field. Little is known about the prevalence and distribution of the adult potential donor population in the United States now that it falls under the oversight of the United Network for Organ Sharing (UNOS). Methods: We assessed the UNOS database from 2008 to 2015 to estimate the prevalence and distribution of adult potential vascularized composite allograft donors. Donor inclusion and exclusion criteria were developed in a way to minimize risk to recipients and were applied to the dataset...
June 2018: Plastic and Reconstructive Surgery. Global Open
Anoma Nellore, Jay A Fishman
Post-transplantation infections are common in allograft recipients and should be expected in all immunocompromised hosts. Based on the need for immunosuppression in xenotransplantation, procedures developed to enhance safety in allotransplantation can be applied in future xenotransplantation clinical trials. Standardized approaches can be developed to guide the evaluation of common infectious syndromes in xenograft recipients. The opportunity created by screening of swine intended as xenograft donors has equal applicability to allotransplantation-notably broader screening strategies for allograft donors such as use of advanced sequencing modalities including broad-range molecular probes, microarrays, and high-throughput pyrosequencing...
July 2018: Xenotransplantation
Sara Salehi, Kenny Tran, Warren L Grayson
In the past, a diagnosis of organ failure would essentially be a death sentence for patients. With improved techniques for organ procurement and surgical procedures, transplantations to treat organ failure have become standard medical practice. However, while the demand for organs has skyrocketed, the donor pool has not kept pace leading to long recipient waiting lists. Organ preservation provides a means to increase the number of available transplantable organs. However, there are significant drawbacks associated with cold storage, the current gold standard...
September 2018: Yale Journal of Biology and Medicine
Maximilian Christopeit, Myriam Labopin, Norbert-Claude Gorin, Francesco Saraceni, Jakob Passweg, Edouard Forcade, Johan Maertens, Maria Teresa Van Lint, Alberto Bosi, Dietger Niederwieser, Gerhard Ehninger, Emmanuelle Polge, Mohamad Mohty, Arnon Nagler
Patients with acute myeloid leukemia (AML) who relapse after autologous stem cell transplantation (ASCT) can be rescued by allogeneic SCT. We identified 537 adult patients with AML allografted in second complete remission (CR2) or first relapse after ASCT in the European Society for Blood and Marrow Transplantation (EBMT) registry and. At 3 years post allograft, leukemia free survival (LFS) was 31.4% [95%CI 27.3-35.6], overall survival (OS) 39.5% [95%CI 35.1-43.9], relapse incidence (RI) 34.6% [95%CI 30.4-38...
September 14, 2018: American Journal of Hematology
Negar Karimaghai, Amin Tamadon, Farhad Rahmanifar, Davood Mehrabani, Alireza Raayat Jahromi, Shahrokh Zare, Zahra Khodabandeh, Iman Razeghian Jahromi, Omid Koohi-Hoseinabadi, Mehdi Dianatpour
Objectives: Adipose tissue-derived mesenchymal stem cells (AT-MSCs) with more potent immunomodulatory effects, greater proliferative potential and secretion of growth factors and cytokines in comparison with bone marrow derived MSCs are more appropriate for cell therapy. The aims of the present study were to evaluate the histomorphometric effect of AT-MSCs allotransplantation on regeneration of germinal layer cells of seminiferous tubules in busulfan-induced azoospermic hamsters. Materials and Methods: In the present experimental case-control study, AT-MSCs were isolated from adipose tissue of two female and six male donor albino hamsters, and testes of the males were simultaneously used as negative control group...
July 2018: Iranian Journal of Basic Medical Sciences
Bin Pan, Fan Xia, Yujing Wu, Fan Zhang, Zhenzhen Lu, Ruixue Fu, Longmei Shang, Lingling Li, Zengtian Sun, Lingyu Zeng, Kailin Xu
Acute graft-versus-host disease (aGVHD) remains a major challenging complication of patients receiving allogeneic hematopoietic cell transplantation (allo-HCT). CD4+ effector T cells and their related cytokines mediate pathogenesis of aGVHD, in which donor-T-cell derived interleukin-22 (IL-22) was recently indicated to play a role. The role of recipient-derived IL-22 in aGVHD remains to be elucidated. By applying IL-22 knock out (IL-22KO) mice as recipients of allotransplant, we found recipient derived IL-22 alleviated aGVHD and improved survival of allotransplant recipients...
August 13, 2018: Cytokine
Charles Anton Fries, Carole Yasay Villamaria, Jerry Richard Spencer, Shari Lawson, Lin Wang, Thomas Raj, E George Wolf, Bijaya Kumar Parida, Vijay Saradhi Gorantla, Rory Frederick Rickard, Michael Robert Davis
BACKGROUND:  Ischemia-reperfusion injury (IRI) precipitates acute rejection of vascularized composite allografts (VCA). Hyperbaric preservation of tissues ex vivo, between harvest and revascularization, may reduce IRI and mitigate acute rejection of VCA. METHODS:  A porcine heterotopic musculocutaneous gracilis flap model was used. In phase 1, control autografts ( n  = 5) were infused with University of Wisconsin Solution (UWS) and stored at 4°C for 3 hours...
August 12, 2018: Journal of Reconstructive Microsurgery
Thomas Kerforne, Geraldine Allain, Sebastien Giraud, Delphine Bon, Virginie Ameteau, Pierre Couturier, William Hebrard, Jerome Danion, Jean-Michel Goujon, Raphael Thuillier, Thierry Hauet, Benoit Barrou, Christophe Jayle
Kidneys from donation after circulatory death (DCD) are highly sensitive to ischemia-reperfusion injury and thus require careful reconditioning, such as Normothermic Regional Perfusion (NRP). However, the optimal NRP protocol remains to be characterized. NRP was modeled in a DCD porcine model (30min of cardiac arrest) for 2h, 4h or 6h compared to a control group (noNRP); kidneys were machine-preserved and allotransplanted. NRP appeared to permit recovery from warm ischemia, possibly due to increased expression of HIF1α-dependent survival pathway...
August 9, 2018: American Journal of Transplantation
D Szubińska-Lelonkiewicz, M Osiak, P Wychowański, M Siewert-Gutowska, P Fiedor
Recipients of allotransplants are more susceptible to viral infections, among which the human papilloma virus infection is an independent factor inducing precancerous lesions and cancers of both the anogenital and the cervicocephalic region. MATERIALS AND METHODS: The study included a group of 69 allogenic kidney transplantation recipients aged 20 to 70, who were treated with cyclosporine, azathioprine, and prednisone. The patients in whom the macroscopic examination of the oral mucosa revealed lesions were qualified for a biopsy...
July 2018: Transplantation Proceedings
Yu-Chi Wang, Rong-Fu Chen, Gerald Brandacher, W P Andrew Lee, Yur-Ren Kuo
BACKGROUND: Our previous studies demonstrated that adipose-derived stem cells (ASCs) could modulate regulatory T cells (Treg) and prolong hind-limb allotransplant survival in vitro and in vivo. Dendritic cells (DCs) play a pivotal role in innate and adaptive immunity. The aim of this study is to investigate the underlying mechanism of ASCs in modulating DC maturation. MATERIALS AND METHODS: ASCs were isolated from rodent adipose tissue, DCs were derived from the bone marrow, and CD4+ T cells were purified from splenocytes...
September 15, 2018: Experimental Cell Research
John S Riley, Lauren E McClain, John D Stratigis, Barbara E Coons, Haiying Li, Heather A Hartman, William H Peranteau
In utero hematopoietic cell transplantation (IUHCT) is a nonmyeloablative nonimmunosuppressive alternative to postnatal hematopoietic stem cell transplantation for the treatment of congenital hemoglobinopathies. Anti-HLA donor-specific Abs (DSA) are associated with a high incidence of graft rejection following postnatal hematopoietic stem cell transplantation. We determine if DSA present in the mother can similarly cause graft rejection in the fetus following IUHCT. Ten million C57BL/6 (B6, H2kb ) bone marrow cells were transplanted in utero into gestational day 14 BALB/c (H2kd ) fetuses...
September 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Yue Zhao, Yu Jia, Lu Wang, Song Chen, Xia Huang, Bingyang Xu, Guangyuan Zhao, Ying Xiang, Jun Yang, Gang Chen
Heme oxygenase-1 (HO-1) is critical for the ability of immature dendritic cells (imDCs) to suppress T-cell responses. Induction of high HO-1 expression may markedly improve the tolerogenic capacity of imDCs. Here, we generated bone marrow-derived DCs (BMDCs) from BALB/c mice with low doses of GM-CSF and IL-4. The adherent BMDCs were obtained as imDCs. Upregulation of HO-1 in imDCs (HO-1hi -imDCs) was achieved by cobalt protoporphyrin treatment. HO-1hi -imDCs proved to be more maturation-resistant than conventional imDCs, with an enhanced ability to inhibit allogeneic T-cell proliferation stimulated by anti-CD3/CD28 antibodies...
2018: Frontiers in Immunology
Xie-Na Cao, Yuan Kong, Yang Song, Min-Min Shi, Hong-Yan Zhao, Qi Wen, Zhong-Shi Lyu, Cai-Wen Duan, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Xiao-Jun Huang
Graft-versus-host disease (GVHD) is a major complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT) that is frequently associated with bone marrow (BM) suppression, and clinical management is challenging. BM endothelial progenitor cells (EPCs) play crucial roles in the regulation of haematopoiesis and thrombopoiesis. However, little is known regarding the functional roles of BM EPCs in acute GVHD (aGVHD) patients. In the current prospective case-control study, reduced and dysfunctional BM EPCs, characterized by decreased migration and angiogenesis capacities and increased levels of reactive oxygen species (ROS) and apoptosis, were found in aGVHD patients compared with those without aGVHD...
July 9, 2018: British Journal of Haematology
Krishna S Vyas, Anita T Mohan, Shane D Morrison, Duy C Tran, Samir Mardini
BACKGROUND:  Dendritic cells (DCs) are bone marrow-derived, professional antigen-presenting cells with tolerogenic function. The ability of DCs to regulate alloantigen-specific T cell responses and to promote tolerance has aligned them ideally for a role in vascularized composite allotransplantation (VCA). In this study, we summarize the current evidence for DC therapies for tolerance induction to alleviate the requirement for chronic immunosuppression. METHOD:  A comprehensive and structured review of manuscripts published on VCA was performed using the MEDLINE and PubMed databases...
October 2018: Journal of Reconstructive Microsurgery
Christian Martin Seitz, Matthias Eyrich, Johann Greil, Patrick Schlegel, Tobias Feuchtinger, Peter Bader, Martin Ebinger, Carl Philipp Schwarze, Paul Gerhardt Schlegel, Michael Schumm, Rupert Handgretinger, Peter Lang
Transplantation of peripheral blood stem cells (PBSC) from matched unrelated donors (MUD) is still associated with a significant risk for graft vs. host disease (GvHD), especially in pediatric patients receiving grafts from adult donors containing high amounts of T cells. Here, we present long-term follow-up results on 25 pediatric patients, (acute leukemia n = 15, NHL n = 3, CML n = 3, MDS n = 5), transplanted with CD34 or CD133 positively selected PBSC from MUDs supplemented with an add-back of 1 × 107 /kg body weight (kgBW) unselected T cells resulting in a median T-cell depletion (TCD) of 1...
May 24, 2018: Bone Marrow Transplantation
Peter Dreger, Mauricette Michallet, Paul Bosman, Sascha Dietrich, Mohamad Sobh, Ariane Boumendil, Arnon Nagler, Christof Scheid, Jan Cornelissen, Dietger Niederwieser, Lutz Müller, Elizabeth Vandenberghe, Ilaria Scortechini, Helene Schoemans, Niels S Andersen, Jürgen Finke, Domenico Russo, Per Ljungman, Jakob Passweg, Michel van Gelder, Nadira Durakovic, Helene Labussiere-Wallet, Tobias Berg, Gerald Wulf, Wolfgang Bethge, Donald Bunjes, Stefan Stilgenbauer, Maria Elisa Canepari, Michel Schaap, Christopher P Fox, Nicolaus Kröger, Silvia Montoto, Johannes Schetelig
The aim of this retrospective study was to investigate the safety and efficacy of allogeneic hematopoietic cell transplantation (alloHCT) in patients pre-treated with ibrutinib. Eligible were patients aged >18 years allotransplanted for chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) after prior exposure to ibrutinib who were registered with the EBMT registry. Seventy patients (CLL 48, MCL 22) were included. At the time of alloHCT, 73% of the patients were ibrutinib responsive. All patients except one engrafted, and acute GVHD grade 2-4 (3-4) was observed in 49% (12%) of 68 evaluable patients...
May 4, 2018: Bone Marrow Transplantation
Paul Lohan, Oliver Treacy, Maurice Morcos, Ellen Donohoe, Yvonne O'donoghue, Aideen E Ryan, Stephen J Elliman, Thomas Ritter, Matthew D Griffin
Mesenchymal stem/stromal cells (MSC) are an immunomodulatory cell population which are under preclinical and clinical investigation for a number of inflammatory conditions including transplantation. In this study, a well-established rat corneal transplantation model was used to test the ability of human MSC to prolong corneal allograft rejection-free survival using a pre-transplant intravenous infusion protocol previously shown to be efficacious with allogeneic rat MSC. Surprisingly, pre-transplant administration of human MSC had no effect on corneal allograft survival...
August 2018: Stem Cells
Silje Johansen, Hilde Kollsete Gjelberg, Aymen Bushra Ahmed, Øystein Bruserud, Håkon Reikvam
Myeloid sarcoma is an extramedullary (EM) manifestation (i.e., manifestation outside the bone marrow) of acute myeloid leukemia (AML); it is assumed to be relatively uncommon and can be the only manifestation of leukemia relapse after allogenic stem cell transplantation (allo-SCT). An EM sarcoma can manifest in any part of the body, although preferentially manifesting in immunological sanctuary sites as a single or multiple tumors. The development of myeloid sarcoma after allo-SCT is associated with certain cytogenetic abnormalities, developing of graft versus host disease (GVHD), and treatment with donor lymphocytes infusion (DLI)...
2018: Case Reports in Oncological Medicine
Guro Kristin Melve, Elisabeth Ersvaer, Kristin Paulsen Rye, Aymen Bushra Ahmed, Einar K Kristoffersen, Tor Hervig, Håkon Reikvam, Kimberley Joanne Hatfield, Øystein Bruserud
BACKGROUND: Peripheral blood stem cells from healthy donors mobilized by granulocyte colony-stimulating factor (G-CSF) and thereafter harvested by leukapheresis are commonly used for allogeneic stem cell transplantation. METHODS: Plasma levels of 38 soluble mediators (cytokines, soluble adhesion molecules, proteases, protease inhibitors) were analyzed in samples derived from healthy stem cell donors before G-CSF treatment and after 4 days, both immediately before and after leukapheresis...
May 2018: Cytotherapy
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