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Transplantation induction therapies

Kevin Rakszawski, Kosuke Miki, David Claxton, Henry Wagner, Hiroko Shike, Shin Mineishi, Seema Naik
Approximately 30-40% of patients with acute myeloid leukemia (AML) experience induction failures. In these patients who do not achieve remission with two cycles of standard induction therapies, the probability of achieving remission with subsequent inductions is very limited. Hematopoietic stem cell transplantation (HSCT) is the only curative option for these patients, but high relapse rate and transplant-related mortality often preclude them to proceed to transplant. Thus, AML not in remission at time of HSCT remains a huge unmet need in current HSCT practice, particularly if the patient does not have an HLA-matched donor identified by the time of two induction failures...
March 14, 2018: International Journal of Hematology
Gary Hin-Fai Yam, Ericia Pei-Wen Teo, Melina Setiawan, Matthew J Lovatt, Nur Zahirah Binte M Yusoff, Matthias Fuest, Bee-Tin Goh, Jodhbir S Mehta
Corneal opacities are a leading cause of global blindness. They are conventionally treated by the transplantation of donor corneal tissue, which is, restricted by a worldwide donor material shortage and allograft rejection. Autologous adult stem cells with a potential to differentiate into corneal stromal keratocytes (CSKs) could offer a suitable choice of cells for regenerative cell therapy. Postnatal periodontal ligament (PDL) contains a population of adult stem cells, which has a similar embryological origin as CSK, that is cranial neural crest...
March 13, 2018: Journal of Cellular and Molecular Medicine
Alexandros Briasoulis, Chakradhari Inampudi, Mohan Pala, Rabea Asleh, Paulino Alvarez, Jay Bhama
Approximately 50% of heart transplant programs currently employ a strategy of induction therapy (IT) with either interleukin-2 receptor antagonists (IL2RA) or polyclonal anti-thymocyte antibodies (ATG) during the early postoperative period. However, the overall utility of such therapy is uncertain and data comparing induction protocols are limited. The authors searched PubMed, the Cochrane Central Register of Controlled Trials, and through January 2018 for randomized controlled trials (RCTs) or observational controlled studies of IT vs no IT and IL2RA vs ATG...
March 13, 2018: Heart Failure Reviews
Paolo Milani, Giampaolo Merlini, Giovanni Palladini
Light chain (AL) amyloidosis is caused by a usually small plasma-cell clone that is able to produce the amyloidogenic light chains. They are able to misfold and aggregate, deposit in tissues in the form of amyloid fibrils and lead to irreversible organ dysfunction and eventually death if treatment is late or ineffective. Cardiac damage is the most important prognostic determinant. The risk of dialysis is predicted by the severity of renal involvement, defined by the baseline proteinuria and glomerular filtration rate, and by the response to therapy...
2018: Mediterranean Journal of Hematology and Infectious Diseases
Gui Pan, Haojie Hao, Jianping Liu
The transplantation of insulin-producing cells (IPCs) or pancreatic progenitor cells is a theoretical therapy for diabetes with insulin insufficiency. Isolated hepatocytes from newborn rats (within 24 h after birth) were progressively induced into IPCs using 5-aza-2'-deoxycytidine, Trichostatin A, retinoic acid, insulin-transferrin-selenium, and nicotinamide. We transplanted Pdx1+ pancreatic progenitors into STZ-induced diabetic mice and found the decreased blood glucose and increased insulin level in comparison with diabetic model...
March 7, 2018: Biochemical and Biophysical Research Communications
Karine Augeul-Meunier, Marie-Lorraine Chretien, Anne-Marie Stoppa, Lionel Karlin, Lofti Benboubker, Jose Miguel Torregrosa Diaz, Mohamad Mohty, Ibrahim Yakoub-Agha, Jacques-Olivier Bay, Aurore Perrot, Claude-Eric Bulabois, Anne Huynh, Mélanie Mercier, Laurent Frenzel, Hervé Avet-Loiseau, Régis Peffault de Latour, Jérôme Cornillon
Renal impairment is a common complication of multiple myeloma (MM), accounting for 20-30% of MM patients at diagnosis and 40-50% of patients during the course of their disease. This feature is associated with poor prognosis and shorter survival as compared to patients with normal renal function (NRF). Therefore, therapeutic management is challenging as autologous stem cell transplantation (ASCT) is often not considered as a valuable strategy, mainly due to concerns of toxicity. In this retrospective and multicenter study, we included 55 MM patients with dialysis-dependent or independent renal failure who underwent high-dose melphalan-based ASCT in order to assess the efficacy outcomes and toxicities of this strategy...
March 9, 2018: Bone Marrow Transplantation
Eirini Katodritou, Evangelos Terpos, Sossana Delimpasi, Maria Kotsopoulou, Eurydiki Michalis, Chrysanthi Vadikolia, Marie-Christine Kyrtsonis, Argiris Symeonidis, Nikolaos Giannakoulas, Chrissa Vadikolia, Michalis Michael, Christina Kalpadakis, Theodora Gougopoulou, Chrystalla Prokopiou, Georgia Kaiafa, Dimitrios Christoulas, Maria Gavriatopoulou, Evlampia Giannopoulou, Vasiliki Labropoulou, Evgenia Verrou, Efstathios Kastritis, Pavlina Konstantinidou, Achilles Anagnostopoulos, Meletios A Dimopoulos
We have studied the efficacy and the prognostic impact of novel agents in 50 primary plasma cell leukemia (pPCL) patients registered in our database. Eighty percent of patients were treated upfront with novel agent-based combinations; 40% underwent autologous stem cell transplantation (ASCT). Objective response rate was 76; 38% achieved at least very good partial response (≥vgPR) and this correlated significantly with bortezomib-based therapy plus ASCT. At the time of evaluation, 40 patients had died. Early mortality rate (≤1 month) was 6%...
March 9, 2018: Blood Cancer Journal
Chao Ren, Peiyuan Yin, Neng Ren, Zhe Wang, Jiahui Wang, Caiyi Zhang, Wei Ge, Deqin Geng, Xiaotong Wang
Recent studies have suggested that the regulation of endogenous neural stem cells (NSCs) or transplanting of exogenous nerve cells are the newest and most promising methods for the treatment of dementia and other neurological diseases. The special location and limited number of endogenous NSCs, however, restrict their clinical application. The success in directional differentiation of exogenous stem cells from other tissue sources into neural cells has provided a novel source for NSCs. Study on the relative mechanisms is still at the preliminary stage...
March 9, 2018: Stem Cell Research & Therapy
Simon Kavanagh, Emily Heath, Rose Hurren, Marcela Gronda, Samir H Barghout, Sanduni U Liyanage, Thirushi P Siriwardena, Jaime Claudio, Tong Zhang, Mahadeo Sukhai, Tracy L Stockley, Suzanne Kamel-Reid, Amr Rostom, Andrzej Lutynski, Dina Khalaf, Anna Rydlewski, Steven M Chan, Vikas Gupta, Dawn Maze, Hassan Sibai, Andre C Schuh, Karen Yee, Mark D Minden, Aaron D Schimmer
We evaluated outcomes of 100 patients with high risk AML treated with Ida-FLAG induction as first-line therapy. 72 achieved remission with one cycle; 19 did not. High risk cytogenetics and TP53 mutations were associated with failure to achieve remission. In those reaching remission, allogeneic bone marrow transplantation was associated with better relapse-free and overall survival. Those not achieving remission with induction therapy were extremely unlikely to reach remission with further therapy and had a dismal prognosis...
February 20, 2018: Leukemia Research
Shuang Zhang, Zhiqiang Zhu, Yufeng Wang, Shi Liu, Chenqiong Zhao, Weijun Guan, Yuhua Zhao
The role of mesenchymal stem cells (MSCs) in cellular therapy is well recognized in this work. MSCs have advantages of high proliferation, clone formation, multi-lineage differentiation and immunosuppression. Furthermore, adipose-resident MSCs (ADSCs) are extensively employed due to its advantages of abundant source, low cost and simple operation. Many researchers have emphasized the role of adipose-resident MSCs in the development of therapies for liver injury, but few attentions were paid on the use of induced functional hepatocytes...
March 7, 2018: Cytotechnology
Chien-Chia Chen, Alice Koenig, Carole Saison, Suzan Dahdal, Guillaume Rigault, Thomas Barba, Morgan Taillardet, Dimitri Chartoire, Michel Ovize, Emmanuel Morelon, Thierry Defrance, Olivier Thaunat
Antibody-mediated rejection is currently the leading cause of transplant failure. Prevailing dogma predicts that B cells differentiate into anti-donor-specific antibody (DSA)-producing plasma cells only with the help of CD4+ T cells. Yet, previous studies have shown that dependence on helper T cells decreases when high amounts of protein antigen are recruited to the spleen, two conditions potentially met by organ transplantation. This could explain why a significant proportion of transplant recipients develop DSA despite therapeutic immunosuppression...
2018: Frontiers in Immunology
Alina Striha, A John Ashcroft, Anna Hockaday, David A Cairns, Karen Boardman, Gwen Jacques, Cathy Williams, John A Snowden, Mamta Garg, Jamie Cavenagh, Kwee Yong, Mark T Drayson, Roger Owen, Mark Cook, Gordon Cook
BACKGROUND: Multiple myeloma (MM) is a plasma cell tumour with an approximate annual incidence of 4500 in the UK. Therapeutic options for patients with MM have changed in the last decade with the arrival of proteasome inhibitors and immunomodulatory drugs. Despite these options, almost all patients will relapse post first-line autologous stem cell transplantation (ASCT). First relapse management (second-line treatment) has evolved in recent years with an expanding portfolio of novel agents, driving response rates influencing the durability of response...
March 7, 2018: Trials
Qipeng Sun, Zhengyu Huang, Fei Han, Ming Zhao, Ronghua Cao, Daqiang Zhao, Liangqing Hong, Ning Na, Heng Li, Bin Miao, Jianmin Hu, Fanhang Meng, Yanwen Peng, Qiquan Sun
BACKGROUND: Kidneys from deceased donors are being used to meet the growing need for grafts. However, delayed graft function (DGF) and acute rejection incidences are high, leading to adverse effects on graft outcomes. Optimal induction intervention should include both renal structure injury repair and immune response suppression. Mesenchymal stem cells (MSCs) with potent anti-inflammatory, regenerative, and immune-modulatory properties are considered a candidate to prevent DGF and acute rejection in renal transplantation...
March 7, 2018: Journal of Translational Medicine
Gaurav Narula, Nirmalaya D Pradhan, Brijesh Arora, Sripad D Banavali
BACKGROUND: Involvement of risk-organs (RO+) in Langerhans cell histiocytosis (LCH) and inadequate early response identifies patients at high risk for relapse and mortality requiring intensive salvage therapy including stem cell transplant, adding cost and toxicity. To mitigate this, we used a standard induction, augmented with metronomic etoposide, and prolonged maintenance-similarly augmented for RO+, and retrospectively analyzed its impact. PROCEDURE: LCH patients from 2009 through 2014 were included...
March 7, 2018: Pediatric Blood & Cancer
Stephanie Ruf, Holger Hebart, Lisa Lyngsie Hjalgrim, Edita Kabickova, Peter Lang, Daniel Steinbach, Georg C Schwabe, Wilhelm Woessmann
Vinblastine and targeted therapies induce remissions in patients with relapsed or progressive anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL). Central nervous system (CNS) prophylaxis often is not included during re-induction in CNS-negative relapse patients. We report on five patients with progressive or early relapsed ALK-positive ALCL who developed CNS progression during re-induction with vinblastine, crizotinib, or brentuximab vedotin given for bridging to allogeneic blood stem cell transplantation...
March 7, 2018: Pediatric Blood & Cancer
D Henrich, C Seebach, R Verboket, A Schaible, I Marzi, H Bonig
Bone marrow mononuclear cells (BMC) seeded on a scaffold of β-tricalcium phosphate (β-TCP) promote bone healing in a critical-size femur defect model. Being BMC a mixed population of predominantly mature haematopoietic cells, which cell type(s) is(are) instrumental for healing remains elusive. Although clinical therapies using BMC are often dubbed as stem cell therapies, whether stem cells are relevant for the therapeutic effects is unclear and, at least in the context of bone repair, seems dubious. Instead, in light of the critical contribution of monocytes and macrophages to tissue development, homeostasis and injury repair, in the current study it was hypothesised that BMC-mediated bone healing derived from the stem cell population...
March 6, 2018: European Cells & Materials
Michaela Oeller, Sandra Laner-Plamberger, Sarah Hochmann, Nina Ketterl, Martina Feichtner, Gabriele Brachtl, Anna Hochreiter, Cornelia Scharler, Lara Bieler, Pasquale Romanelli, Sebastien Couillard-Despres, Elisabeth Russe, Katharina Schallmoser, Dirk Strunk
Intravascular transplantation of tissue factor (TF)-bearing cells elicits an instant blood-mediated inflammatory reaction (IBMIR) resulting in thrombotic complications and reduced engraftment. Here we studied the hemocompatibility of commonly used human white adipose tissue (WAT), umbilical cord (UC) and bone marrow stromal cells (BMSC) and devised a possible strategy for safe and efficient stromal cell transplantation. Methods: Stromal cell identity, purity, and TF expression was tested by RTQ-PCR, flow cytometry and immunohistochemistry...
2018: Theranostics
Masato Habuka, Yoko Wada, Yoichi Kurosawa, Suguru Yamamoto, Yusuke Tani, Riuko Ohashi, Yoichi Ajioka, Masaaki Nakano, Ichiei Narita
BACKGROUND: Visceral disseminated varicella zoster viral (VZV) infection is a rare but severe complication with a high mortality rate in immunosuppressed individuals, and an increased susceptibility to VZV has been reported in kidney transplant recipients who are treated with mycophenolate mofetil (MMF). In Japan, MMF is currently approved for patients with lupus nephritis (LN) and data to indicate its optimal dosage are still insufficient. CASE PRESENTATION: A 46-year-old Japanese woman with rheumatoid arthritis was diagnosed as having systemic lupus erythematosus (SLE) and LN class III (A/C)...
March 5, 2018: BMC Research Notes
Matt Stevenson, Abdullah Pandor, Jean Hamilton, John Stevens, Clare Rowntree, Marrissa Martyn-St James, Andrew Rawdin, Ruth Wong
As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer (Incyte Corporation) of ponatinib (Inclusig® ) to submit evidence of its clinical and cost effectiveness for previously treated Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) and chronic myeloid leukaemia. This paper focusses on Ph+ ALL. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent evidence review group (ERG)...
March 3, 2018: PharmacoEconomics
Tiziana A L Brevini, Georgia Pennarossa, Elena F M Manzoni, Fulvio Gandolfi
Type 1 Diabetes Mellitus (T1DM) is a chronic disease that leads to loss of insulin secreting β-cells, causing high levels of blood glucose. Exogenous insulin administration is not sufficient to mimic the normal function of β-cells and, consequently, diabetes mellitus often progresses and can lead to major chronic complications and morbidity. The physiological control of glucose levels can only be restored by replacing the β-cell mass.We recently developed a new strategy that allows for epigenetic conversion of dermal fibroblasts into insulin-secreting cells (EpiCC), using a brief exposure to the demethylating agent 5-aza-cytidine (5-aza-CR), followed by a pancreatic induction protocol...
March 3, 2018: Advances in Experimental Medicine and Biology
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