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Bone marrow transplant complications

P Dhakal, V R Bhatt
Diagnosis and management of hematopoietic cell transplant-associated thrombotic microangiopathy (TA-TMA) are very complex and controversial, given multiple ongoing issues and comorbidities in sick transplant recipients. Complement activation via classic and alternative pathways is emerging as a potential pathogenetic mechanism in the development of TA-TMA. Complement-centric diagnostic strategy using functional and genetic tests may possibly support diagnosis, enhance molecular understanding and direct drug development...
October 24, 2016: Bone Marrow Transplantation
Min-Min Shi, Yuan Kong, Yang Song, Yu-Qian Sun, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang
Poor graft function (PGF) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Murine studies suggest that endothelial progenitor cells (EPCs) are preferential supporting cells for hematopoietic stem cells (HSCs) in the bone marrow (BM) microenvironment. Our previous work found that a reduced number of BM EPCs was an independent risk factor for the occurrence of PGF after allo-HSCT. However, little is known about the functional role of BM EPCs and how to improve impaired BM EPCs in PGF...
October 21, 2016: Blood
Shang-Chun Guo, Shi-Cong Tao, Wen-Jing Yin, Xin Qi, Jia-Gen Sheng, Chang-Qing Zhang
Osteonecrosis of the femoral head (ONFH) represents a debilitating complication following glucocorticoid (GC)-based therapy. Synovial-derived mesenchymal stem cells (SMSCs) can exert protective effect in the animal model of GC-induced ONFH by inducing cell proliferation and preventing cell apoptosis. Recent studies indicate the transplanted cells exert therapeutic effects primarily via a paracrine mechanism and exosomes are an important paracrine factor that can be directly used as therapeutic agents for tissue engineering...
2016: International Journal of Biological Sciences
Bin Shen, Yu Zhang, Wei Dai, Yupo Ma, Yongping Jiang
BACKGROUND: Hematopoietic CD34(+) stem cells are widely used in the clinical therapy of complicated blood diseases. Stem cell factor Sall4B is a zinc finger transcription factor that plays a vital role in hematopoietic stem cell expansion. The purpose of our current study is to further evaluate how Sall4B might affect the expansion of CD34(+) cells derived from nonhuman primates. METHODS: Sall4B was overexpressed in nonhuman primate bone marrow-derived CD34(+) cells via a lentiviral transduction system...
October 20, 2016: Stem Cell Research & Therapy
Qing-Shuo Zhang, Weiliang Tang, Matthew Deater, Ngoc Phan, Andrea N Marcogliese, Hui Li, Muhsen Al-Dhalimy, Angela Major, Susan Olson, Raymond J Monnat, Markus Grompe
Fanconi anemia is an inherited bone marrow failure disorder associated with a high incidence of leukemia and solid tumors. Bone marrow transplantation is currently the only curative therapy for the hematopoietic complications of this disorder. However, long-term morbidity and mortality remain very high and new therapeutics are badly needed. Here we show that the widely used diabetes drug metformin improves hematopoiesis and delays tumor formation in Fancd2(-/-) mice. Metformin is the first compound reported to improve both of these Fanconi anemia phenotypes...
October 18, 2016: Blood
Jie Qin, Yusuke Arakawa, Miwa Morita, John J Fung, Shiguang Qian, Lina Lu
BACKGROUND: Islet transplantation is a promising therapeutic approach for restore the physical response to blood glucose in type 1 diabetes. Current chronic use of immunosuppressive reagents for preventing islet allograft rejection is associated with severe complications. In addition, many of the immunosuppressive drugs are diabetogenic. The induction of transplant tolerance to eliminate the dependency on immunosuppression is ideal, but remains challenging. METHODS: Addition of hepatic stellate cells allowed generation of myeloid-derived suppressor cells (MDSC) from precursors in mouse bone marrow...
October 17, 2016: Transplantation
Andrew C Dietz, Christine N Duncan, Blanche P Alter, Dorine Bresters, Morton J Cowan, Luigi Notarangelo, Philip S Rosenberg, Shalini Shenoy, Roderick Skinner, Mark C Walters, John Wagner, K Scott Baker, Michael A Pulsipher
An international consensus conference sponsored by the Pediatric Blood and Marrow Transplant consortium entitled, "Late Effects Screening and Recommendations Following Allogeneic Hematopoietic Cell Transplant for Immune Deficiency and Non-malignant Hematologic Disease was held in Minneapolis, Minnesota on May 10-11, 2016. The purpose of the conference was to address the unmet need for a greater understanding of and the screening for long-term complications in the growing population of survivors of transplantation for non-malignant disorders...
October 10, 2016: Biology of Blood and Marrow Transplantation
Y Mori, K Ikeda, T Inomata, G Yoshimoto, N Fujii, H Ago, T Teshima
Jak1/2 inhibitor ruxolitinib is a promising agent for treating steroid-refractory GvHD after allogeneic hematopoietic stem cell transplantation (SCT) to produce quick and durable responses. However, optimal dose and tapering schedule of ruxolitinib remain to be determined. Discontinuation of ruxolitinib in myelofibrosis often induces 'withdrawal syndrome' characterized by acute relapse of the disease, but this issue is not well addressed in the treatment of GvHD. Four patients with GvHD (one acute and three chronic) after SCT for myelofibrosis were treated with ruxolitinib...
October 10, 2016: Bone Marrow Transplantation
Suelen Martins Perobelli, Ana Carolina Terra Mercadante, Rômulo Gonçalves Galvani, Triciana Gonçalves-Silva, Ana Paula Gregório Alves, Antonio Pereira-Neves, Marlene Benchimol, Alberto Nóbrega, Adriana Bonomo
Acute graft-versus-host disease (aGVHD) is the main complication of allogeneic hematopoietic stem cell transplantation, and many efforts have been made to overcome this important limitation. We showed previously that G-CSF treatment generates low-density splenic granulocytes that inhibit experimental aGVHD. In this article, we show that aGVHD protection relies on incoming IL-10(+) neutrophils from G-CSF-treated donor spleen (G-Neutrophils). These G-Neutrophils have high phagocytic capacity, high peroxide production, low myeloperoxidase activity, and low cytoplasmic granule content, which accounts for their low density...
October 5, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Sonia Halioui-Louhaichi, Ons Azzabi, Nadia Mattoussi, Hasna Labiadh, Khadija Bousseta, Neji Tebib, Taher Gargah, Sayda Ben Becher, Mohamed Ridha Barbouch, Mohamed Bejaoui, Ahmed Maherzi
Background Primary immunodeficiencies (PID) are a group of heterogeneous and relatively rare diseases. Aim to determine the clinical characteristics, outcome and genetic data of primary immunodeficiencies in pediatrics patients. Methods A retrospective, descriptive and multicentered study, enrolling 33 children presenting a PID in Tunis, during a period of 22 years (1991-2012). Resultats a masculine predominance has been noticed with a sex ratio at 2,3. Consanguinity was found in 71% of family cases. History of early infant deaths was found in 42% of cases...
April 2016: La Tunisie Médicale
Laëtitia Le Texier, Katie E Lineburg, Benjamin Cao, Cameron McDonald-Hyman, Lucie Leveque-El Mouttie, Jemma Nicholls, Michelle Melino, Blessy C Nalkurthi, Kylie A Alexander, Bianca Teal, Stephen J Blake, Fernando Souza-Fonseca-Guimaraes, Christian R Engwerda, Rachel D Kuns, Steven W Lane, Michele Teng, Charis Teh, Daniel Gray, Andrew D Clouston, Susan K Nilsson, Bruce R Blazar, Geoffrey R Hill, Kelli P A MacDonald
Regulatory T cells (Tregs) play a crucial role in the maintenance of peripheral tolerance. Quantitative and/or qualitative defects in Tregs result in diseases such as autoimmunity, allergy, malignancy, and graft-versus-host disease (GVHD), a serious complication of allogeneic stem cell transplantation (SCT). We recently reported increased expression of autophagy-related genes (Atg) in association with enhanced survival of Tregs after SCT. Autophagy is a self-degradative process for cytosolic components that promotes cell homeostasis and survival...
September 22, 2016: JCI Insight
Yutaro Hino, Noriko Doki, Yasushi Senoo, Noritaka Sekiya, S Kurosawa, Satoshi Tsuboi, Kazuteru Ohashi
Nocardiosis is a rare bacterial infection occurring mainly in patients with deficient cell-mediated immunity. Although disseminated nocardiosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a rare complication, it is associated with high mortality. Moreover, after allo-HSCT, nocardiosis may be mistaken for other bacterial or fungal infections because clinical and radiographic findings of pulmonary, cerebral, and cutaneous nocardiosis lesions are non-specific. Here, we report a case of disseminated nocardiosis (caused by Nocardia abscessus) with skin, pulmonary, liver, lymph node, and multiple brain abscesses in a patient after allo-HSCT...
October 1, 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Stavroula Masouridi-Levrat, Federico Simonetta, Yves Chalandon
Bone marrow failure (BMF) syndromes are severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this paper, we distinguish two different entities, the graft failure (GF) and the poor graft function (PGF), and we review the current understanding of the interactions between the immune and hematopoietic compartments in these conditions. We first discuss how GF occurs as the result of classical alloreactive immune responses mediated by residual host cellular and humoral immunity persisting after conditioning and prevented by host and donor regulatory T cells...
2016: Frontiers in Immunology
Dasaradha Jalapothu, Margherita Boieri, Rachel E Crossland, Pranali Shah, Isha A Butt, Jean Norden, Ralf Dressel, Anne M Dickinson, Marit Inngjerdingen
MicroRNAs (miRNA) have emerged as central regulators of diverse biological processes and contribute to driving pathology in several diseases. Acute graft-versus-host disease (aGvHD) represents a major complication after allogeneic hematopoietic stem cell transplantation, caused by alloreactive donor T cells attacking host tissues leading to inflammation and tissue destruction. Changes in miRNA expression patterns occur during aGvHD, and we hypothesized that we could identify miRNA signatures in target tissues of aGvHD that may potentially help understand the underlying molecular pathology of the disease...
2016: Frontiers in Immunology
Nicolas Noiseux, Samer Mansour, Richard Weisel, Louis-Mathieu Stevens, Shant Der Sarkissian, Katherine Tsang, Andrew M Crean, Eric Larose, Shu-Hong Li, Bernd Wintersperger, Minh Quan Vu, Ignacio Prieto, Ren-Ke Li, Denis Claude Roy, Terrence M Yau
OBJECTIVES: The IMPACT-CABG trial is the first North American multicenter phase II randomized study of intramyocardial delivery of autologous CD133(+) stem cells in patients with chronic ischemic cardiomyopathy undergoing coronary artery bypass grafting. The primary objective was to demonstrate safety, including freedom from major adverse cardiac events. The secondary objective was to evaluate feasibility of same-day autologous cell preparation. Although the trial was not powered to evaluate LV function, exploratory data were collected...
August 13, 2016: Journal of Thoracic and Cardiovascular Surgery
Rosangela Invernizzi, Raffaella Bastia, Federica Quaglia
A case of parvovirus B19-induced pure red cell aplasia occurring in a heart transplant recipient is reported. The diagnosis of this rare but clinically important complication can be suspected on the basis of the pathognomonic morphological features of the bone marrow.
September 2016: Clinical Case Reports
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...
September 19, 2016: Bone Marrow Transplantation
Mehrdad Saravi, Mohsen Vakili Sadeghi, Hassan Mahmoodi Nesheli
Bone marrow transplantation (BMT) in young children improves results in β-thalassemia major. Graft versus host disease (GVHD) is an important complication of peripheral blood stem cell transplantation. GVHD affects heart with a behavior resembling an autoimmune disease, including pericardial effusion. We describe a 22-year-old β-thalassemia major patient who underwent bone marrow transplantation with an HLA-identical sibling donor. The patient didn't have any serious problem until 15 months after transplantation...
September 2016: Archives of Iranian Medicine
Margherita Boieri, Pranali Shah, Ralf Dressel, Marit Inngjerdingen
Bone marrow transplantation (BMT) is the only therapeutic option for many hematological malignancies, but its applicability is limited by life-threatening complications, such as graft-versus-host disease (GvHD). The last decades have seen great advances in the understanding of BMT and its related complications; in particular GvHD. Animal models are beneficial to study complex diseases, as they allow dissecting the contribution of single components in the development of the disease. Most of the current knowledge on the therapeutic mechanisms of BMT derives from studies in animal models...
2016: Frontiers in Immunology
Jonas Paludo, Utkarsh Painuly, Shaji Kumar, Wilson I Gonsalves, Vincent Rajkumar, Francis Buadi, Martha Q Lacy, Angela Dispenzieri, Robert A Kyle, Michelle L Mauermann, Arleigh McCurdy, David Dingli, Ronald S Go, Suzanne R Hayman, Nelson Leung, John A Lust, Yi Lin, Morie A Gertz, Prashant Kapoor
INTRODUCTION: Limited data exist with respect to the outcome and optimal treatment of patients with myelomatous involvement of the central nervous system (CNS). MATERIALS AND METHODS: Of 4060 patients with multiple myeloma (MM), evaluated at Mayo Clinic from 1998 to 2014, 29 (0.7%) had identifiable CNS involvement, established by the presence of atypical plasma cells in the cerebrospinal fluid (CSF) and/or identification of intraparenchymal or meningeal involvement on magnetic resonance imaging (MRI)...
August 10, 2016: Clinical Lymphoma, Myeloma & Leukemia
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