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Chronic GVHD

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https://www.readbyqxmd.com/read/27905258/hla-mismatched-haploidentical-transplantation-using-low-dose-anti-thymocyte-globulin-atg-thymoglobulin
#1
Shinichi Kako, Yu Akahoshi, Naonori Harada, Hirofumi Nakano, Kazuaki Kameda, Tomotaka Ugai, Ryoko Yamasaki, Hidenori Wada, Yuko Ishihara, Koji Kawamura, Kana Sakamoto, Miki Sato, Masahiro Ashizawa, Kiriko Terasako-Saito, Shun-Ichi Kimura, Misato Kikuchi, Hideki Nakasone, Rie Yamazaki, Junya Kanda, Yoshinobu Kanda
Objectives To clarify optimal strategies for human leukocyte antigen (HLA)-mismatched haploidentical hematopoietic stem cell transplantation (HSCT). Methods Twelve patients who underwent HSCT from a haploidentical related donor using low-dose thymoglobulin were analyzed retrospectively. Thymoglobulin was added to conditioning regimens at 2.5 mg/kg/day for 2 days (days -4 and -3). Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine and methotrexate. Results The median age of the patients was 33 years...
December 1, 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27899803/novel-targets-in-the-treatment-of-chronic-graft-versus-host-disease
#2
REVIEW
A Im, F T Hakim, S Z Pavletic
Despite advances that have improved survival after allogeneic hematopoietic stem cell transplantation (HCT), chronic graft-versus-host disease (GVHD) remains a leading cause of late morbidity and mortality after transplant. Current treatment options show limited efficacy in steroid-refractory disease, and there exists a paucity of robust data to guide management decisions. Lack of United States Food and Drug Administration (FDA) or European Medicines Agency (EMA) approved agents in GVHD underscore the importance of developing novel therapies...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27888016/post-transplantation-cyclophosphamide-and-ixazomib-combination-rescues-mice-subjected-to-experimental-gvhd-and-is-superior-to-either-agent-alone
#3
A Samer Al-Homsi, Austin Goodyke, Michael McLane, Sarah Abdel-Mageed, Kelli Cole, Marlee Muilenburg, Yuxin Feng
Lapses in the prevention of graft-versus-host disease (GvHD) following allogeneic hematopoietic stem cell transplantation (HSCT) warrants novel approaches. Such approaches include, among others, the use of post-transplantation cyclophosphamide (PTC) and proteasome inhibitors. Although PTC alone consistently produces low rates of chronic GvHD, the incidence of acute GvHD remains significant. Inversely, prolonged post-transplantation administration of proteasome inhibitors carries a risk of paradoxical aggravation of GvHD...
November 22, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27888014/nonmyeloablative-haploidentical-bone-marrow-transplantation-with-post-transplant-cyclophosphamide-for-pediatric-and-young-adult-patients-with-high-risk-hematologic-malignancies
#4
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 (PT/Cy) from 2003-2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplant immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus...
November 22, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27879990/sequential-chemotherapy-followed-by-reduced-intensity-conditioning-and-allogeneic-haematopoietic-stem-cell-transplantation-in-adult-patients-with-relapse-or-refractory-acute-myeloid-leukaemia-a-survey-from-the-acute-leukaemia-working-party-of-ebmt
#5
Olle Ringdén, Myriam Labopin, Christoph Schmid, Behnam Sadeghi, Emmanuelle Polge, Johanna Tischer, Arnold Ganser, Mauricette Michallet, Lothar Kanz, Rainer Schwerdtfeger, Arnon Nagler, Mohamad Mohty
This study analysed the outcome of 267 patients with relapse/refractory acute myeloid leukaemia (AML) who received sequential chemotherapy including fludarabine, cytarabine and amsacrine followed by reduced-intensity conditioning (RIC) and allogeneic haematopoietic stem cell transplantation (HSCT). The transplants in 77 patients were from matched sibling donors (MSDs) and those in 190 patients were from matched unrelated donors. Most patients (94·3%) were given anti-T-cell antibodies. The incidence of acute graft-versus-host disease (GVHD) of grades II-IV was 32·1% and that of chronic GVHD was 30·2%...
November 23, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27872734/allogeneic-hematopoietic-stem-cell-transplantation-for-adult-patients-with-fanconi-anemia
#6
Hosein Kamranzadeh Fumani, Mohammad Zokaasadi, Amir Kasaeian, Kamran Alimoghaddam, Asadollah Mousavi, Babak Bahar, Mohammad Vaezi, Ardeshir Ghavamzadeh
BACKGROUND AND OBJECTIVES: Fanconi anemia (FA) is a rare genetic disorder caused by an impaired DNA repair mechanism which leads to an increased tendency toward malignancies and progressive bone marrow failure. The only curative management available for hematologic abnormalities in FA patients is hematopoietic stem cell transplantation (HSCT). This study aimed to report the results of HSCT in adult or adolescent FA patients. PATIENTS AND METHODS: Twenty FA patients with ages of 16 or more who underwent HSCT between 2002 and 2015 enrolled in this study...
2016: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/27872728/what-unrelated-hematopoietic-stem-cell-transplantation-in-thalassemia-taught-us-about-transplant-immunogenetics
#7
REVIEW
Giorgio La Nasa, Adriana Vacca, Roberto Littera, Eugenia Piras, Sandro Orru, Marianna Greco, Carlo Carcassi, Giovanni Caocci
Although the past few decades have shown an improvement in the survival and complication-free survival rates in patients with beta-thalassemia major and gene therapy is already at an advanced stage of experimentation, hematopoietic stem cell transplantation (HSCT) continues to be the only effective and realistic approach to the cure of this chronic non-malignant disease. Historically, human leukocyte antigen (HLA)-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with HSCT from other sources...
2016: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/27862740/poor-immune-reconstitution-is-associated-with-symptomatic-bk-polyomavirus-viruria-in-allogeneic-stem-cell-transplant-recipients
#8
Ala Abudayyeh, Amir Hamdi, Maen Abdelrahim, Heather Lin, Valda D Page, Gabriela Rondon, Borje S Andersson, Aimaz Afrough, Charles S Martinez, Jeffrey J Tarrand, Dimitrios P Kontoyiannis, David Marin, A Osama Gaber, Betul Oran, Roy F Chemaly, Sairah Ahmed, Islam Abudayyeh, Amanda Olson, Roy Jones, Uday Popat, Richard E Champlin, Elizabeth J Shpall, Katayoun Rezvani
BACKGROUND: BK polyomavirus (BKPyV) infections are known indicators of immune suppression in hematopoietic stem cell transplant (HSCT) recipients; they can lead to hemorrhagic cystitis, ureteral stenosis, renal dysfunction, and prolonged hospital stays. In this study, we determined transplant-associated variables and immune parameters that can predict for the risk of BKPyV viruria. We hypothesized that BKPyV infection is a marker of poor immune recovery. METHODS: We analyzed all engrafted patients undergoing first allogeneic HSCT at MD Anderson Cancer Center in Houston between January 2004 and December 2012...
November 14, 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/27861297/extracorporeal-photopheresis-for-treatment-of-acute-and-chronic-graft-versus-host-disease-an-italian-multicentric-retrospective-analysis-on-94-patients-on-behalf-of-the-gruppo-italiano-trapianto-di-midollo-osseo
#9
Michele Malagola, Valeria Cancelli, Cristina Skert, Pierino Ferremi Leali, Emilio Ferrari, Alessandra Tiburzi, Maria Luisa Sala, Irene Donnini, Patrizia Chiusolo, Alberto Mussetti, Marta Battista, Alessandro Turra, Federica Cattina, Benedetta Rambaldi, Francesca Schieppati, Nicola Polverelli, Simona Bernardi, Simone Perucca, Mirella Marini, Daniele Laszlo, Chiara Savignano, Francesca Patriarca, Paolo Corradini, Nicola Piccirillo, Simona Sica, Alberto Bosi, Domenico Russo
BACKGROUND: Extracorporeal photopheresis (ECP) is considered a valid second-line treatment for acute and chronic graft versus host disease (GVHD). METHODS: Ninety-four patients with acute GVHD (aGVHD) (n = 45) and chronic GVHD (cGVHD) (n = 49), retrospectively recruited in 6 Italian centers, were submitted to ECP for second-line treatment. At the time of ECP, 22 (49%) and 23 (51%) of 45 patients with aGHVD were nonresponsive and in partial remission (PR) after steroids, respectively, and all the 49 patients with cGVHD were steroid refractory...
December 2016: Transplantation
https://www.readbyqxmd.com/read/27856368/haploidentical-transplantation-with-post-transplant-cyclophosphamide-for-high-risk-acute-lymphoblastic-leukemia
#10
Samer A Srour, Denái R Milton, Asad Bashey, Amado Karduss-Urueta, Monzr Al Malki, Rizwan Romee, Scott Solomon, Stacey Brown, Michael Slade, Rosendo Perez, Gabriela Rondon, Stephan J Forman, Richard E Champlin, Partow Kebriaei, Stefan O Ciurea
Haploidentical transplantation performed with post-transplantation cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis has been associated with favorable outcomes for patients with acute myeloid leukemia and lymphomas. However, it remains unclear if such approach is effective for patients with acute lymphoblastic leukemia (ALL). We analyzed outcomes of 109 consecutively treated ALL patients 18 years of age and older at 5 institutions. The median age was 32 years and the median follow-up for survivors was 13 months...
November 14, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27846611/comparable-composite-endpoints-after-hla-matched-and-hla-haploidentical-transplantation-with-posttransplantation-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 posttransplant 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, posttransplantation cyclophosphamide reduces severe graft-versus-host disease after allogeneic marrow transplantation, making its composite endpoints of particular interest. We retrospectively analyzed 684 adults with hematologic malignancies who received T-cell-replete bone marrows and posttransplantation cyclophosphamide after myeloablative HLA-matched related (n= 192) or unrelated (n=120), or nonmyeloablative HLA-haploidentical (n = 372) donor transplantation; median follow up was 4 (range 0...
October 20, 2016: Haematologica
https://www.readbyqxmd.com/read/27833447/immune-recovery-and-the-risk-of-cmv-ebv-reactivation-in-children-post-allogeneic-haematopoietic-stem-cell-transplantation
#12
Małgorzata Janeczko, Monika Mielcarek, Blanka Rybka, Renata Ryczan-Krawczyk, Dorota Noworolska-Sauren, Krzysztof Kałwak
Immune reconstitution was studied prospectively in 86 children who underwent allogeneic haematopoietic stem cell transplantation (HSCT). We analysed the risk of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation in correlation with the kinetics of immune recovery and in relation to other potential risk factors that may influence the reactivation of these viruses including: diagnosis, type of HSCT, source of stem cells, type of conditioning, or the occurrence of graft-versus-host disease (GvHD)...
2016: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/27832981/haploidentical-bone-marrow-transplantation-with-post-transplant-cyclophosphamide-for-children-and-adolescents-with-fanconi-anemia
#13
Carmem Bonfim, Lisandro Ribeiro, Samantha Nichele, Gisele Loth, Marco Bitencourt, Adriana Koliski, Cilmara Kuwahara, Ana Luiza Fabro, Noemi F Pereira, Daniela Pilonetto, Monica Thakar, Hans-Peter Kiem, Kristin Page, Ephraim J Fuchs, Mary Eapen, Ricardo Pasquini
We describe haplo-identical bone marrow transplantation with post-transplant cyclophosphamide (PT-CY) for 30 patients with Fanconi anemia (FA). Twenty-six were transplanted upfront and the preparatory regimens included fludarabine (FLU) 150mg/m(2) + total body irradiation (TBI) 200-300cGy +/- CY 10mg/kg without (n=12) or with rabbit ATG (r-ATG) 4-5mg/kg (n=14). Four patients were rescued after primary or secondary graft failure after related or unrelated donor transplantation with above regimen with (n=2) or without r-ATG (n=2)...
November 7, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27827824/plasma-biomarkers-of-risk-for-death-in-a-multicenter-phase-3-trial-with-uniform-transplant-characteristics-post-allogeneic-hct
#14
Mohammad Abu Zaid, Juan Wu, Cindy Wu, Brent R Logan, Jeffrey Yu, Corey Cutler, Joseph H Antin, Sophie Paczesny, Sung Won Choi
A phase 3 clinical trial (BMT CTN 0402) comparing tacrolimus/sirolimus (Tac/Sir) versus tacrolimus/methotrexate (Tac/Mtx) as graft-versus-host disease (GVHD) prophylaxis after matched-related allogeneic hematopoietic cell transplantation (HCT) recently showed no difference between study arms in acute GVHD-free survival. Within this setting of a prospective, multicenter study with uniform GVHD prophylaxis, conditioning regimen, and donor source, we explored the correlation of 10 previously identified biomarkers with clinical outcomes after allogeneic HCT...
November 8, 2016: Blood
https://www.readbyqxmd.com/read/27821507/introduction-to-a-review-series-chronic-gvhd-from-pathogenic-bcr-signaling-to-novel-therapeutic-targets
#15
Robert Zeiser, Robert S Negrin
No abstract text is available yet for this article.
November 7, 2016: Blood
https://www.readbyqxmd.com/read/27821505/mechanistic-approaches-for-prevention-and-treatment-of-chronic-gvhd
#16
Corey S Cutler, John Koreth, Jerome Ritz
Clinical outcomes for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) continue to improve, but chronic graft versus host disease (GVHD) remains a common toxicity and major cause of non-relapse morbidity and mortality. Treatment of chronic GVHD has previously relied primarily on corticosteroids and other broadly immune suppressive agents. However, conventional immune suppressive agents have limited clinical efficacy in chronic GVHD and prolonged immune suppressive treatments result in additional toxicities that further limit clinical recovery from transplant and return to normal daily function...
November 7, 2016: Blood
https://www.readbyqxmd.com/read/27821504/chronic-graft-versus-host-disease-biological-insights-from-pre-clinical-and-clinical-studies
#17
Kelli P A MacDonald, Geoffrey R Hill, Bruce R Blazar
With the increasingly use of mismatched, unrelated and G-CSF mobilized peripheral blood stem cell donor grafts and successful treatment of older recipients, chronic graft-versus-host disease (cGVHD) has emerged as the major cause of non-relapse mortality and morbidity. Chronic GVHD is characterized by lichenoid changes and fibrosis that affects a multitude of tissues, compromising organ function. Beyond steroids, effective treatment options are limited. Thus new strategies to both prevent and treat disease are urgently required...
November 7, 2016: Blood
https://www.readbyqxmd.com/read/27821503/classification-systems-for-chronic-graft-versus-host-disease
#18
Stephanie J Lee
Chronic graft versus host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Clinically, chronic GVHD is a pleiotropic, multi-organ syndrome involving tissue inflammation and fibrosis that often results in permanent organ dysfunction. Chronic GVHD is fundamentally caused by replacement of the host's immune system with donor cells, although the heterogeneity of clinical manifestations suggests patient, donor and transplant factors modulate the phenotype...
November 7, 2016: Blood
https://www.readbyqxmd.com/read/27821187/long-term-survival-and-late-events-after-allogeneic-stem-cell-transplantation-from-hla-matched-siblings-for-acute-myeloid-leukemia-with-myeloablative-compared-to-reduced-intensity-conditioning-a-report-on-behalf-of-the-acute-leukemia-working-party-of-european
#19
Avichai Shimoni, Myriam Labopin, Bipin Savani, Liisa Volin, Gerhard Ehninger, Jurgen Kuball, Donald Bunjes, Nicolaas Schaap, Stephane Vigouroux, Andrea Bacigalupo, Hendrik Veelken, Jorge Sierra, Matthias Eder, Dietger Niederwieser, Mohamad Mohty, Arnon Nagler
BACKGROUND: Myeloablative (MAC) and reduced-intensity conditioning (RIC) are established approaches for allogeneic stem cell transplantation (SCT) in acute myeloid leukemia (AML). Most deaths after MAC occur within the first 2 years after SCT, while patients surviving leukemia-free for 2 years can expect a favorable long-term outcome. However, there is paucity of data on the long-term outcome (beyond 10 years) and the pattern of late events following RIC due to the relative recent introduction of this approach...
November 8, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27819684/tacrolimus-plus-sirolimus-with-or-without-atg-as-gvhd-prophylaxis-in-hla-mismatched-unrelated-donor-allogeneic-stem-cell-transplantation
#20
M A Kharfan-Dabaja, R Parody, J Perkins, O Lopez-Godino, L Lopez-Corral, L Vazquez, D Caballero, J Falantes, J Shapiro, G Ortí, P Barba, D Valcárcel, A Esquirol, R Martino, J L Piñana, C Solano, A Tsalatsanis, J Pidala, C Anasetti, J A Perez-Simón
HLA-matched related or unrelated donors are not universally available. Consequently, patients can be offered hematopoietic stem cell transplantation (HSCT) from alternative donors, including mismatched unrelated donors (MMURD), known to cause a higher incidence of acute GVHD (aGVHD) and chronic GVHD. In vivo T-cell-depletion strategies, such as antithymocyte globulin (ATG) therapy, significantly decrease the risk of GVHD. We performed a multicenter, retrospective study comparing tacrolimus (TAC) and sirolimus (SIR) with or without ATG in 104 patients (TAC-SIR=45, TAC-SIR-ATG=59) who underwent MMURD HSCT...
November 7, 2016: Bone Marrow Transplantation
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