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Hematopoietic stem cell transplantation

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https://www.readbyqxmd.com/read/27913534/myelodysplastic-and-myeloproliferative-disorders-of-childhood
#1
Henrik Hasle
Myelodysplastic syndrome (MDS) and myeloproliferative disorders are rare in children; they are divided into low-grade MDS (refractory cytopenia of childhood [RCC]), advanced MDS (refractory anemia with excess blasts in transformation), and juvenile myelomonocytic leukemia (JMML), each with different characteristics and management strategies. Underlying genetic predisposition is recognized in an increasing number of patients. Germ line GATA2 mutation is found in 70% of adolescents with MDS and monosomy 7. It is challenging to distinguish RCC from aplastic anemia, inherited bone marrow failure, and reactive conditions...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913519/transplantation-for-myelodysplastic-syndromes-who-when-and-which-conditioning-regimens
#2
Wael Saber, Mary M Horowitz
Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative therapy for myelodysplastic syndrome (MDS). Broad application is hindered by high risks of transplant-related morbidity and mortality, especially in the older age range represented by the MDS population. However, recent advances in strategies to minimize regimen-related toxicity make HCT a viable option for many more patients. Appropriate selection of patients involves consideration of patient factors, including use of geriatric assessment tools and comorbidity scales, that predict risks of regimen-related toxicity as well as disease factors, including genetic markers, which predict survival with both non-HCT and HCT therapy...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913517/treatment-of-low-risk-myelodysplastic-syndromes
#3
Valeria Santini
The majority of myelodysplastic syndrome (MDS) patients belong to the International Prognostic Scoring System (IPSS) and IPSS-revised (IPSS-R) lower-risk categories. Their precise diagnostics and prognostic stratification is often a challenge, but may ensure the optimization of therapy. The availability of diverse treatment options has significantly improved the quality of life and survival of this group of patients. Anemia is the most relevant cytopenia in terms of frequency and symptoms in lower-risk MDS, and may be treated successfully with erythropoietic stimulating agents, provided a careful selection is performed on the basis of IPSS-R, endogenous erythropoietin levels, and transfusion independence...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913469/can-we-make-a-better-match-or-mismatch-with-kir-genotyping
#4
Rohtesh S Mehta, Katayoun Rezvani
Natural killer (NK) cell function is regulated by a fine balance between numerous activating and inhibitory receptors, of which killer-cell immunoglobulin-like receptors (KIRs) are among the most polymorphic and comprehensively studied. KIRs allow NK cells to recognize downregulation or the absence of HLA class I molecules on target cells (known as missing-self), a phenomenon that is commonly observed in virally infected cells or cancer cells. Because KIR and HLA genes are located on different chromosomes, in an allogeneic environment such as after hematopoietic stem cell transplantation, donor NK cells that express an inhibitory KIR for an HLA class I molecule that is absent on recipient targets (KIR/KIR-ligand mismatch), can recognize and react to this missing self and mediate cytotoxicity...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913467/transplantation-for-bone-marrow-failure-current-issues
#5
Régis Peffault de Latour
The preferred treatment of idiopathic aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA)-identical sibling donor. Transplantation from a well-matched unrelated donor (MUD) may be considered for patients without a sibling donor after failure of immunosuppressive therapy, as may alternative transplantation (mismatched, cord blood or haplo-identical HSCT) for patients without a MUD. HSCT may also be contemplated for congenital disorders in cases of pancytopenia or severe isolated cytopenia...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913465/aplastic-anemia-and-clonal-evolution-germ-line-and-somatic-genetics
#6
Akiko Shimamura
Clonal progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) remains a dreaded complication for a subset of patients with bone marrow failure (BMF). Recognizing risk factors for the development of MDS or AML would inform individualized treatment decisions and identify patients who may benefit from early or upfront hematopoietic stem cell transplantation. Now that next-generation DNA sequencing is available in the clinical laboratory, research has focused on the implications of germ line and somatic mutations for diagnosing and monitoring patients with BMF...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913459/children-with-rare-diseases-of-neutrophil-granulocytes-from-therapeutic-orphans-to-pioneers-of-individualized-medicine
#7
Christoph Klein
Neutrophil granulocytes are the most abundant immune cells in the blood yet the pathways orchestrating their differentiation and biological function remain incompletely understood. Studying (ultra-) rare patients with monogenetic defects of neutrophil granulocytes may open new horizons to understand basic principles of hematopoiesis and innate immunity. Here, recent insights into genetic factors controlling myelopoiesis and their more general role in biology will be presented in a clinical perspective. Advances in supportive care, first and foremost the use of recombinant human granulocyte-colony stimulating factor, has made a substantial difference for the quality of life and life expectancy of patients with congenital neutropenia (CN)...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913458/therapy-related-myeloid-neoplasms-does-knowing-the-origin-help-to-guide-treatment
#8
Michael Heuser
Therapy-related myeloid neoplasms (t-MN) combine t-MDS and therapy related acute myeloid leukemia (t-AML) patients in one entity because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis. Treatment with epipodophyllotoxins like etoposide has been associated with a short interval between treatment and development of t-AML, with fusion oncogenes like KMT2A/MLL-MLLT3 and a better prognosis. In contrast, treatment with alkylating agents has been associated with a longer latency, an initial MDS phase, adverse cytogenetics, and a poor prognosis...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912993/rehabilitation-in-chronic-graft-versus-host-disease
#9
REVIEW
Sean Robinson Smith, Arash Asher
Chronic graft-versus-host disease is a potentially debilitating complication of allogeneic hematopoietic stem cell transplantation. Due to the direct inflammatory effects of the disease on tissue, and the impact on muscle and bone of the high-dose glucocorticoid immunosuppression used to treat the disease, patients are at risk of developing multifactorial functional impairment. This review outlines the clinical assessment and rehabilitation interventions to manage aspects of the disease that cause the most impairment: involvement of the skin/fascial and cardiopulmonary organ systems, as well as steroid-induced myopathy and bone and joint destruction...
February 2017: Physical Medicine and Rehabilitation Clinics of North America
https://www.readbyqxmd.com/read/27912953/evaluating-the-effect-of-matricaria-recutita-and-mentha-piperita-herbal-mouthwash-on-management-of-oral-mucositis-in-patients-undergoing-hematopoietic-stem-cell-transplantation-a-randomized-double-blind-placebo-controlled-clinical-trial
#10
Maria Tavakoli Ardakani, Sara Ghassemi, Mahshid Mehdizadeh, Faraz Mojab, Jamshid Salamzadeh, Samaneh Ghassemi, Abbas Hajifathali
OBJECTIVES: To investigate the effects of Matricaria recutita and Mentha piperita on oral mucositis (OM) in patients undergoing hematopoietic stem cell transplantation (HSCT). DESIGN: Randomized double blind placebo controlled clinical trial. SETTING: Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, and Bone Marrow Transplantation Center at Taleghani Teaching Hospital, Tehran, Iran. PARTICIPANTS: Sixty patients undergoing HSCT were randomly assigned to two groups: placebo (n=33), and herbal mouthwash group (n=27)...
December 2016: Complementary Therapies in Medicine
https://www.readbyqxmd.com/read/27912759/intestinal-dysbiosis-and-allogeneic-hematopoietic-progenitor-cell-transplantation
#11
REVIEW
Vikram M Raghunathan, Iris Sheng, Seah H Lim
The intestinal microbiota is a diverse and dynamic ecosystem that is increasingly understood to play a vital role in human health. Hematopoietic stem cell transplant recipients undergo prolonged exposure to antimicrobials, chemotherapeutic agents, and immunosuppressants, resulting in profound shifts in the gut microbiome. A growing body of research has revealed the ways in which these microbiologic shifts shape immune modulation, affecting susceptibility to infections and graft-versus-host disease, the two major post-transplant complications in this population...
December 3, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27912088/enhancing-stem-cell-transplantation-with-nutri-technology
#12
Valter D Longo, Salvatore Cortellino
It is necessary to employ myeloablative irradiation or chemotherapy to deplete the HSC niche to optimize hematopoietic stem cell transplantation. In a recent issue of Science, Taya and colleagues provide evidence for an alternative to the toxic chemoirradiative procedure by showing that a valine-restricted diet is sufficient to empty the bone marrow niche.
December 1, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27912084/fetal-to-adult-hematopoiesis-with-the-flk-of-a-switch
#13
Stijn Vanhee, Joan Yuan
Blood development relies on discrete stem and progenitor cell populations with unclear lineage relationships and distinct functional characteristics that change during ontogeny. In this issue of Cell Stem Cell, Beaudin et al. (2016) identify a hematopoietic stem cell population with fetal characteristics that is developmentally restricted yet capable of long-term multi-lineage reconstitution upon transplantation into adult recipients.
December 1, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27909887/similar-outcome-after-allogeneic-stem-cell-transplantation-with-a-modified-flamsa-conditioning-protocol-substituting-4%C3%A2-gy-tbi-with-treosulfan-in-an-elderly-population-with-high-risk-aml
#14
Udo Holtick, Marco Herling, Natali Pflug, Geothy Chakupurakal, Silke Leitzke, Dominik Wolf, Michael Hallek, Christof Scheid, Jens M Chemnitz
The fludarabine, amsacrine, and cytarabine (FLAMSA)-reduced-intensity conditioning (RIC) protocol has been described to be effective in patients with high-risk and refractory acute myeloic leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (aSCT). To increase safety and tolerability of the conditioning, we previously reported the feasibility to substitute the TBI component by treosulfan in elderly AML patients. We now present long-term follow-up data on patients treated with FLAMSA/treosulfan compared to the original FLAMSA/4Gy TBI protocol...
December 1, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27909435/immune-reconstitution-after-allogeneic-hematopoietic-stem-cell-transplantation
#15
REVIEW
Justyna Ogonek, Mateja Kralj Juric, Sakhila Ghimire, Pavankumar Reddy Varanasi, Ernst Holler, Hildegard Greinix, Eva Weissinger
The timely reconstitution and regain of function of a donor-derived immune system is of utmost importance for the recovery and long-term survival of patients after allogeneic hematopoietic stem cell transplantation (HSCT). Of note, new developments such as umbilical cord blood or haploidentical grafts were associated with prolonged immunodeficiency due to delayed immune reconstitution, raising the need for better understanding and enhancing the process of immune reconstitution and finding strategies to further optimize these transplant procedures...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27909215/cure-for-thalassemia-major-from-allogeneic-hematopoietic-stem-cell-transplantation-to-gene-therapy
#16
Alok Srivastava, Ramachandran V Shaji
Allogeneic hematopoietic stem cell transplantation has been established for several decades as a gene replacement therapy for patients with thalassemia major and now offers very high rates of cure to those who are able to access this therapy. Outcomes have improved tremendously over the last decade even in high-risk patients. The limited data available suggests that the long-term outcome is also excellent with >90% survival but for best results, hematopoietic stem cell transplantation should be offered early before any end organ damage occurs...
December 1, 2016: Haematologica
https://www.readbyqxmd.com/read/27907031/in-vitro-pre-clinical-validation-of-suicide-gene-modified-anti-cd33-redirected-chimeric-antigen-receptor-t-cells-for-acute-myeloid-leukemia
#17
Kentaro Minagawa, Muhammad O Jamil, Mustafa Al-Obaidi, Larisa Pereboeva, Donna Salzman, Harry P Erba, Lawrence S Lamb, Ravi Bhatia, Shin Mineishi, Antonio Di Stasi
BACKGROUND: Approximately fifty percent of patients with acute myeloid leukemia can be cured with current therapeutic strategies which include, standard dose chemotherapy for patients at standard risk of relapse as assessed by cytogenetic and molecular analysis, or high-dose chemotherapy with allogeneic hematopoietic stem cell transplant for high-risk patients. Despite allogeneic hematopoietic stem cell transplant about 25% of patients still succumb to disease relapse, therefore, novel strategies are needed to improve the outcome of patients with acute myeloid leukemia...
2016: PloS One
https://www.readbyqxmd.com/read/27906865/management-of-post-transplant-lymphoproliferative-disorders
#18
Gabriela Llaurador, Lauren McLaughlin, Birte Wistinghausen
PURPOSE OF REVIEW: Post-transplant lymphoproliferative disease (PTLD) is a major complication of hematopoietic stem cell and solid organ transplantation. The incidence of transplantation in childhood has been steadily rising, making PTLD the most common form of lymphoproliferation in childhood. The purpose of this review is to summarize the role of the Epstein-Barr virus (EBV) in the pathophysiology and discuss the management of PTLD. RECENT FINDINGS: More than 90% of pediatric PTLD is EBV-positive...
November 30, 2016: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/27906795/factors-determining-the-outcome-of-hematopoietic-stem-cell-transplantation-in-patients-with-acute-lymphoblastic-leukemia-at-king-faisal-specialist-hospital-and-research-center-riyadh-saudi-arabia
#19
Suleimman Al-Sweedan, Amal Al-Seraihy, Ali Al-Ahmari, Abdullah Al-Jefri, Viqaruddin Mohammed, Rafat Jafri, Khawar Siddiqui, Mouhab Ayas
Medical records of 82 patients with acute lymphoblastic leukemia (ALL) who underwent hematopoietic cell transplantation (HCT) at our institution from 2005 to 2011 were reviewed. Forty-five patients were male (54.8%). The median age at HCT was 7.46 years (range, 0.98 to 14.31 y), the median time to HCT after diagnosis was 12.56 months. Ten patients were below the age of 1 year (12%). All patients were in complete remission at the time of HCT. In 83 transplants, 64 patients received HCT from human leukocyte antigen-identical-related donors and 19 from other donors...
November 30, 2016: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/27906171/combined-nifuroxazide-and-sat05f-therapy-reduces-graft-versus-host-disease-after-experimental-allogeneic-bone-marrow-transplantation
#20
Huijie Jia, Tiesuo Zhao, Yinghua Ji, Xiaolong Jia, Wenjing Ren, Chen Li, Minming Li, Yali Xiao, Hui Wang, Kailin Xu
Acute graft-versus-host disease (aGvHD) is the major barrier to the broader use of allogenetic hematopoietic stem cells. However, currently these are no highly specific and efficient drugs. Monotherapy is not sufficient and more efficient and safe therapeutic regimen are urgent need. Studies demonstrated TLR9 and Stat3 signal pathways are critical for antigen-presenting cell maturation and T-cell activation, which are important mediators in aGvHD. Specific block these two critical signal pathways using their inhibitors SAT05f and nifuroxazide may be the novel strategies for aGvHD therapy...
December 1, 2016: Cell Death & Disease
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