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graft versus host disease prevention prophylaxis

Franco Aversa, Lucia Prezioso, Ilenia Manfra, Federica Galaverna, Angelica Spolzino, Alessandro Monti
The advantage of using a Human Leukocyte Antigen (HLA)-mismatched related donor is that almost every patient who does not have an HLA-identical donor or who urgently needs hematopoietic stem cell transplantation (HSCT) has at least one family member with whom shares one haplotype (haploidentical) and who is promptly available as a donor. The major challenge of haplo-HSCT is intense bi-directional alloreactivity leading to high incidences of graft rejection and graft-versus-host disease (GVHD). Advances in graft processing and pharmacologic prophylaxis of GVHD have reduced these risks and have made haplo-HSCT a viable alternative for patients lacking a matched donor...
2016: Mediterranean Journal of Hematology and Infectious Diseases
Yuki Asano-Mori
Invasive fungal infections (IFIs) are one of the most serious complications developing after allogeneic hematopoietic stem cell transplantation (allo-HSCT). They are difficult to treat once present and usually have a fatal course in profoundly immunosuppressed patients. Upfront prevention therefore plays an important role in overcoming this threat. The combination of a protected environment and antifungal prophylaxis against Candida spp. is conventionally applied to prevent IFIs during the neutropenic period after HSCT, whereas mold-active agents are recommended for prophylaxis against Aspergillus spp...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Mª Carmen Herrero-Sánchez, Concepción Rodríguez-Serrano, Julia Almeida, Laura San Segundo, Susana Inogés, Ángel Santos-Briz, Jesús García-Briñón, Luis Antonio Corchete, Jesús F San Miguel, Consuelo Del Cañizo, Belén Blanco
BACKGROUND: Graft-versus-host disease (GvHD) remains the major obstacle to successful allogeneic hematopoietic stem cell transplantation, despite of the immunosuppressive regimens administered to control T cell alloreactivity. PI3K/AKT/mTOR pathway is crucial in T cell activation and function and, therefore, represents an attractive therapeutic target to prevent GvHD development. Recently, numerous PI3K inhibitors have been developed for cancer therapy. However, few studies have explored their immunosuppressive effect...
October 20, 2016: Journal of Hematology & Oncology
Juan Gea-Banacloche, Krishna Komanduri, Paul Carpenter, Sophie Paczesny, Stefanie Sarantopoulos, Jo-Anne Young, Nahed El Kassar, Robert Q Le, Kirk Schultz, Linda M Griffith, Bipin Savani, John R Wingard
Immune reconstitution after hematopoietic stem cell transplantation (HCT) beyond 1 year is not completely understood. Many transplant recipients who are free of graft-versus-host disease (GVHD) and not receiving any immunosuppression more than 1 year after transplantation seem to be able to mount appropriate immune responses to common pathogens and respond adequately to immunizations. However, 2 large registry studies over the last 2 decades seem to indicate that infection is a significant cause of late mortality in some patients, even in the absence of concomitant GVHD...
October 14, 2016: Biology of Blood and Marrow Transplantation
Li Wang, Zhenyang Gu, Xiaoli Zhao, Nan Yang, Feiyan Wang, Ailing Deng, Shasha Zhao, Lan Luo, Huaping Wei, Lixun Guan, Zhe Gao, Yonghui Li, Lili Wang, Daihong Liu, Chunji Gao
Mesenchymal stromal cells (MSCs) are attractive agents for the prophylaxis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, safety concerns remain about their clinical application. In this study, we explored whether extracellular vesicles released from human umbilical cord-derived MSCs (hUC-MSC-EVs) could prevent aGVHD in a mouse model of allo-HSCT. hUC-MSC-EVs were intravenously administered to recipient mice on days 0 and 7 after allo-HSCT, and the prophylactic effects of hUC-MSC-EVs were assessed by observing the in vivo manifestations of aGVHD, histologic changes in target organs, and recipient mouse survival...
December 15, 2016: Stem Cells and Development
Li Wang, Haiyan Zhang, Lixun Guan, Shasha Zhao, Zhenyang Gu, Huaping Wei, Zhe Gao, Feiyan Wang, Nan Yang, Lan Luo, Yonghui Li, Lili Wang, Daihong Liu, Chunji Gao
A meta-analysis of animal models was conducted to evaluate the prophylactic effects of mesenchymal stem cells (MSCs) on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation. A total of 50 studies involving 1848 animals were included. The pooled results showed that MSCs significantly reduced aGVHD-associated mortality (risk ratio = 0.70, 95% confidence interval 0.62 to 0.79, P = 2.73×10-9) and clinical scores (standardized mean difference = -3.60, 95% confidence interval -4...
August 12, 2016: Oncotarget
J Whangbo, J Ritz, A Bhatt
Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many patients with severe benign and malignant hematologic disorders. The success of allogeneic HSCT is limited by the development of transplant-related complications such as acute graft-versus-host disease (GvHD). Early pre-clinical studies suggested that intestinal microflora contribute to the pathogenesis of acute GvHD, and that growth suppression or eradication of intestinal bacteria prevented the development of acute GvHD even in MHC-mismatched transplants...
August 15, 2016: Bone Marrow Transplantation
Pooja Khandelwal, Tsuyoshi Fukuda, Kana Mizuno, Ashley Teusink-Cross, Parinda A Mehta, Rebecca A Marsh, Angela D M Kashuba, Alexander A Vinks, Stella M Davies
Maraviroc is an allosteric small molecule antagonist of chemokine receptor type 5 (CCR5) and has been used in adult allogeneic hematopoietic stem cell transplant (HSCT) recipients to prevent acute graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract and liver. The goal of this study was to establish feasibility and pharmacokinetic and pharmacodynamic profiles of maraviroc in pediatric HSCT recipients. Children ages 2 to 12 years were enrolled and maraviroc was added to standard GVHD prophylaxis, which included a calcineurin inhibitor and either steroids or mycophenolate mofetil...
October 2016: Biology of Blood and Marrow Transplantation
Sameh Gaballa, Isabell Ge, Riad El Fakih, Jonathan E Brammer, Piyanuch Kongtim, Ciprian Tomuleasa, Sa A Wang, Dean Lee, Demetrios Petropoulos, Kai Cao, Gabriela Rondon, Julianne Chen, Aimee Hammerstrom, Lindsey Lombardi, Gheath Alatrash, Martin Korbling, Betul Oran, Partow Kebriaei, Sairah Ahmed, Nina Shah, Katayoun Rezvani, David Marin, Qaiser Bashir, Amin Alousi, Yago Nieto, Muzaffar Qazilbash, Chitra Hosing, Uday Popat, Elizabeth J Shpall, Issa Khouri, Richard E Champlin, Stefan O Ciurea
BACKGROUND: High-dose, post-transplantation cyclophosphamide (PTCy) to prevent graft-versus-host disease (GVHD) has improved outcomes in haploidentical (HAPLO) stem cell transplantation (SCT). However, it remains unclear whether this strategy is effective in SCT from 1-antigen human leukocyte antigen (HLA)-mismatched unrelated donors (9/10 MUD) and how the outcomes of these patients compare with those of haploidentical transplantation recipients. METHODS: A parallel, 2-arm, nonrandomized phase 2 clinical trial was conducted of melphalan-based reduced-intensity conditioning with PTCy, tacrolimus, and mycophenolate mofetil to prevent GVHD in patients with high-risk hematologic malignancies who underwent HAPLO (n = 60) or 9/10 MUD (n = 46) SCT...
November 15, 2016: Cancer
Ugur Sahin, Selami Kocak Toprak, Pinar Ataca Atilla, Erden Atilla, Taner Demirer
Infections are the most common and significant cause of mortality and morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The presence of neutropenia and mucosal damage are the leading risk factors in the early pre-engraftment phase. In the early post-engraftment phase, graft versus host disease (GvHD) induced infection risk is increased in addition to catheter related infections. In the late phase, in which reconstitution of cellular and humoral immunity continues, as well as the pathogens seen during the early post-engraftment phase, varicella-zoster virus and encapsulated bacterial infections due to impaired opsonization are observed...
August 2016: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Shun-Ichi Kimura
Invasive aspergillosis (IA) is still one of the leading causes of morbidity and mortality in hematological patients, although its outcome has been improving. Prolonged and profound neutropenia in patients receiving intensive chemotherapy for acute leukemia and stem cell transplantation is a major risk factor for IA. Allogeneic stem cell transplant recipients with graft-versus-host disease and corticosteroid use are also at high risk. Management in a protective environment with high efficiency particular air (HEPA) filter is generally recommended to prevent aspergillosis in patients with prolonged and profound neutropenia...
2016: Medical Mycology Journal
Erin Gatza, Sung Won Choi
Allogeneic hematopoietic cell transplantation (HCT) is an important therapeutic option for malignant and non-malignant diseases, but the more widespread application of the therapy remains limited by the occurrence of graft versus host disease (GVHD). GVHD results from immune-mediated injury by donor immune cells against tissues in the HCT recipient, and can be characterized as acute or chronic depending on the time of onset and site of organ involvement. The majority of efforts have focused on GVHD prevention...
August 2015: International Journal of Hematologic Oncology
Sophie Servais, Yves Beguin, Loic Delens, Grégory Ehx, Gilles Fransolet, Muriel Hannon, Evelyne Willems, Stéphanie Humblet-Baron, Ludovic Belle, Frédéric Baron
INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (alloHSCT) offers potential curative treatment for a wide range of malignant and nonmalignant hematological disorders. However, its success may be limited by post-transplant acute graft-versus-host disease (aGVHD), a systemic syndrome in which donor's immune cells attack healthy tissues in the immunocompromised host. aGVHD is one of the main causes of morbidity and mortality after alloHSCT. Despite standard GVHD prophylaxis regimens, aGVHD still develops in approximately 40-60% of alloHSCT recipients...
August 2016: Expert Opinion on Investigational Drugs
Ching-Hsun Wang, Feng-Yee Chang, Tsu-Yi Chao, Woei-Yau Kao, Ching-Liang Ho, Yeu-Chin Chen, Ming-Shen Dai, Ping-Ying Chang, Yi-Ying Wu, Jung-Chung Lin
BACKGROUND: The aim of this study was to compare the risk factors and clinical outcomes of bacteremia in allogeneic and autologous hematopoietic stem cell transplant (allo-HSCT and auto-HSCT) recipients with levofloxacin prophylaxis during the early period after transplantation. METHODS: Characteristics of bacteremia within 45 days after transplantation between allo-HSCT and auto-HSCT recipients who received levofloxacin prophylaxis between January 2005 and December 2014 were retrospectively reviewed...
March 17, 2016: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
Ying-Jun Chang, Lan-Ping Xu, Yu Wang, Xiao-Hui Zhang, Huan Chen, Yu-Hong Chen, Feng-Rong Wang, Wei Han, Yu-Qian Sun, Chen-Hua Yan, Fei-Fei Tang, Xiao-Dong Mo, Kai-Yan Liu, Xiao-Jun Huang
PURPOSE: This study evaluated whether a prophylaxis strategy directed by the graft-versus-host disease (GVHD) biomarker might reduce the 100-day incidence of acute GVHD grades II to IV. PATIENTS AND METHODS: This controlled, open-label, randomized trial included 228 patients who underwent haploidentical transplantation. On the basis of bone marrow allogeneic graft CD4:CD8 ratios, patients were categorized as low risk (n = 83; group A) or high risk (n = 145). Patients at high risk were randomly assigned to either receive (n = 72; group B) or not receive (n = 73; group C) low-dose corticosteroid prophylaxis...
June 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Nina Worel
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for a variety of malignant and non-malignant hematological and congenital diseases. Due to the fact that the human leukocyte antigen system is inherited independently of the blood group system, approximately 40-50% of all HSCTs are performed across the ABO blood group barrier. The expected immune-hematological consequences after transplantation of an ABO-mismatched stem cell graft are immediate and delayed hemolytic complications due to presence of isohemagglutinins or passenger lymphocyte syndrome...
January 2016: Transfusion Medicine and Hemotherapy
Ying-Jun Chang, Xiao-Jun Huang
Haploidentical stem cell transplantation (haplo-SCT) with an anti-thymocyte globulin (ATG) preparative regimen is associated with induced immune tolerance, rapid hematopoietic recovery, effective prevention of graft-versus-host disease (GVHD), and lower non-relapse mortality (NRM). This has become a common and successfully applied protocol in patients with hematological diseases undergoing haplo-SCT. Survival rates among patients who undergo unmanipulated haploidentical blood and marrow transplantation (HBMT) with anti-thymocyte globulin (ATG)-based regimens are comparable to those following human leukocyte antigen (HLA)-matched sibling transplantation or unrelated donor transplantation...
April 2016: Seminars in Hematology
Robert Zeiser, Bruce R Blazar
Despite major advances in recent years, graft-versus-host disease (GVHD) remains a major life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT). To improve our therapeutic armory against GVHD, preclinical evidence is most frequently generated in mouse and large animal models of GVHD. However, because every model has shortcomings, it is important to understand how predictive the different models are and why certain findings in these models could not be translated into the clinic...
June 23, 2016: Blood
Rohtesh S Mehta, Rima M Saliba, Julianne Chen, Gabriela Rondon, Aimee E Hammerstrom, Amin Alousi, Muzaffar Qazilbash, Qaiser Bashir, Sairah Ahmed, Uday Popat, Chitra Hosing, Issa Khouri, Elizabeth J Shpall, Richard E Champlin, Stefan O Ciurea
Post-transplantation cyclophosphamide (PTCy) is an effective strategy to prevent graft-versus-host disease (GVHD) after haploidentical haematopoietic cell transplantation (HCT). We determined the efficacy of PTCy-based GVHD prophylaxis in human leucocyte antigen (HLA)-mismatched unrelated donor (MMUD) HCT. We analysed 113 adult patients with high-risk haematological malignancies who underwent one-antigen MMUD transplantation between 2009 and 2013. Of these, 41 patients received PTCy, tacrolimus and mycophenolate mofetil (MMF) for GVHD prophylaxis; 72 patients received conventional prophylaxis with anti-thymocyte globulin, tacrolimus and methotrexate...
May 2016: British Journal of Haematology
Emre Tekgündüz, Ali Hakan Kaya, Sinem Civriz Bozdağ, Şerife Koçubaba, Ömür Kayıkçı, Sinem Namdaroğlu, Bilge Uğur, Seval Akpınar, Hikmetullah Batgi, Filiz Bekdemir, Fevzi Altuntaş
There is some preliminary evidence, that veno-occlusive disease prophylaxis with defibrotide (DF) may also have a role in decreasing risk of acute graft-versus-host disease (aGvHD) by preventing tissue damage. In this study, we aimed to investigate the role of DF prophylaxis on the development of aGvHD at D+180. One hundred ninety-five consecutive adult patients receiving allogeneic HCT were retrospectively evaluated in 3 groups: no DF, DF/post-HCT (DF D+1 to D+14) and DF/pre-HCT (DF for 14 days concurrently with conditioning)...
February 2016: Transfusion and Apheresis Science
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