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https://www.readbyqxmd.com/read/28229282/clinical-studies-in-hematologic-microtransplantation
#1
REVIEW
Kevin A David, Dennis Cooper, Roger Strair
The anti-tumor effects of allogeneic hematopoietic stem cell transplantation depend upon engraftment of donor cells followed by a graft-versus-tumor (GVT) effect. However, pre-clinical and clinical studies have established that under certain circumstances, anti-tumor responses can occur despite the absence of high levels of durable donor cell engraftment. Tumor response with little or no donor engraftment has been termed "microtransplantation." It has been hard to define conditions leading to tumor responses without donor cell persistence in humans because the degree of engraftment depends very heavily upon many patient-specific factors, including immune status and degree of prior therapy...
February 22, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28224765/dysregulation-of-telomere-lengths-and-telomerase-activity-in-myelodysplastic-syndrome
#2
Hee Sue Park, Jungeun Choi, Cha Ja See, Jung Ah Kim, Si Nae Park, Kyongok Im, Sung Min Kim, Dong Soon Lee, Sang Mee Hwang
BACKGROUND: Telomere shortening is thought to be involved in the pathophysiology of myeloid malignancies, but telomere lengths (TL) during interphase and metaphase in hematopoietic malignancies have not been analyzed. We aimed to assess the TLs of interphase and metaphase cells of MDS and telomerase activity (TA) and to find out prognostic significances of TL and TA. METHODS: The prognostic significance of TA by quantitative PCR and TL by quantitative fluorescence in situ hybridization (QFISH) of interphase nuclei and metaphase chromosome arms of bone marrow cells from patients with MDS were evaluated...
May 2017: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/28224273/over-expression-of-mir-196b-5p-is-significantly-associated-with-the-progression-of-myelodysplastic-syndrome
#3
Jing Wen, Ying Huang, Hongying Li, Xupai Zhang, Peng Cheng, Donghong Deng, Zhigang Peng, Jun Luo, Weihua Zhao, Yongrong Lai, Zhenfang Liu
Myelodysplastic syndrome (MDS) is a clonal stem cell disorder characterized by ineffective hematopoiesis with a high risk of transformation to acute myeloid leukemia (AML). miRNAs function as tumor suppressors and oncogenes in various cancers and regulate the differentiation potential of hematopoietic stem and progenitor cells (HSPCs). It has been suggested that miRNAs may play an important role in progression of MDS. We analyzed bone marrow samples collected from MDS patients according to different risk stratification indicated by the International Prognostic Scoring System (IPSS)...
February 21, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28223820/flt3-inhibitors-clinical-potential-in-acute-myeloid-leukemia
#4
REVIEW
Marie-Anne Hospital, Alexa S Green, Thiago T Maciel, Ivan C Moura, Anskar Y Leung, Didier Bouscary, Jerome Tamburini
Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy that is cured in as few as 15%-40% of cases. Tremendous improvements in AML prognostication arose from a comprehensive analysis of leukemia cell genomes. Among normal karyotype AML cases, mutations in the FLT3 gene are the ones most commonly detected as having a deleterious prognostic impact. FLT3 is a transmembrane tyrosine kinase receptor, and alterations of the FLT3 gene such as internal tandem duplications (FLT3-ITD) deregulate FLT3 downstream signaling pathways in favor of increased cell proliferation and survival...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28223278/impact-of-genetic-alterations-in-stem-cell-transplantation-for-myelodysplasia-and-secondary-acute-myeloid-leukemia
#5
Tetsuichi Yoshizato, Yasuhito Nannya, Yoshiko Atsuta, Yusuke Shiozawa, Yuka Iijima-Yamashita, Kenichi Yoshida, Yuichi Shiraishi, Hiromichi Suzuki, Yasunobu Nagata, Yusuke Sato, Nobuyuki Kakiuchi, Keitaro Matsuo, Makoto Onizuka, Keisuke Kataoka, Kenichi Chiba, Hiroko Tanaka, Hiroo Ueno, Masahiro M Nakagawa, Bartlomiej Przychodzen, Claudia Haferlach, Wolfgang Kern, Kosuke Aoki, Hidehiro Itonaga, Yoshinobu Kanda, Mikkael A Sekeres, Jaroslaw P Maciejewski, Torsten Haferlach, Yasushi Miyazaki, Keizo Horibe, Masashi Sanada, Satoru Miyano, Hideki Makishima, Seishi Ogawa
Genetic alterations, including mutations and copy number alterations, are central to the pathogenesis of myelodysplastic syndromes and related diseases (myelodysplasia), but their roles in allogeneic stem-cell transplantation have not fully been studied in a large cohort of patients. We enrolled 797 patients who had been diagnosed with myelodysplasia at initial presentation and received transplantation via the Japan Marrow Donor Program. Targeted-capture sequencing was performed to identify mutations in 69 genes, together with copy number alterations, whose effects on transplantation outcomes were investigated...
February 21, 2017: Blood
https://www.readbyqxmd.com/read/28221862/randomized-phase-ii-study-of-clofarabine-based-consolidation-for-younger-adults-with-acute-myeloid-leukemia-in-first-remission
#6
Xavier Thomas, Stéphane de Botton, Sylvie Chevret, Denis Caillot, Emmanuel Raffoux, Emilie Lemasle, Jean-Pierre Marolleau, Céline Berthon, Arnaud Pigneux, Norbert Vey, Oumedaly Reman, Marc Simon, Christian Recher, Jean-Yves Cahn, Olivier Hermine, Sylvie Castaigne, Karine Celli-Lebras, Norbert Ifrah, Claude Preudhomme, Christine Terré, Hervé Dombret
Purpose To evaluate the efficacy and safety of a clofarabine-based combination (CLARA) versus conventional high-dose cytarabine (HDAC) as postremission chemotherapy in younger patients with acute myeloid leukemia (AML). Patients and Methods Patients age 18 to 59 years old with intermediate- or unfavorable-risk AML in first remission and no identified donor for allogeneic stem-cell transplantation (SCT) were eligible. Two hundred twenty-one patients were randomly assigned to receive three CLARA or three HDAC consolidation cycles...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28220349/clofarabine-based-chemotherapy-as-a-bridge-to-transplant-in-the-setting-of-refractory-or-relapsed-acute-myeloid-leukemia-after-at-least-one-previous-unsuccessful-salvage-treatment-containing-fludarabine-a-single-institution-experience
#7
Alfredo Molteni, Marta Riva, Emanuele Ravano, Laura Marbello, Valentina Mancini, Giovanni Grillo, Elisa Zucchetti, Rosa Greco, Roberto Cairoli
For refractory or relapsed acute myeloid leukemia patients, allogeneic hematopoietic stem cell transplantation is the only curative treatment option, but the disease must be in remission before this can be attempted. "Salvage" therapy regimens containing high-dose cytarabine plus fludarabine or cladribine with or without anthracyclines or plus mitoxantrone and etoposide fail in 30-50% of cases. We report the outcome of 14 patients treated with a clofarabine-based treatment administered after at least one failed fludarabine-based "salvage" attempt in a "real life" (outside a clinical trial) context...
February 20, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28220124/in-vivo-efficacy-of-umbilical-cord-blood-stem-cell-derived-nk-cells-in-the-treatment-of-metastatic-colorectal-cancer
#8
John P Veluchamy, Silvia Lopez-Lastra, Jan Spanholtz, Fenna Bohme, Nina Kok, Daniëlle A M Heideman, Henk M W Verheul, James P Di Santo, Tanja D de Gruijl, Hans J van der Vliet
Therapeutic monoclonal antibodies against the epidermal growth factor receptor (EGFR) act by inhibiting EGFR downstream signaling and by eliciting a natural killer (NK) cell-mediated antitumor response. The IgG1 mAb cetuximab has been used for treatment of RAS(wt) metastatic colorectal cancer (mCRC) patients, showing limited efficacy. In the present study, we address the potential of adoptive NK cell therapy to overcome these limitations investigating two allogeneic NK cell products, i.e., allogeneic activated peripheral blood NK cells (A-PBNK) and umbilical cord blood stem cell-derived NK cells (UCB-NK)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28219225/-effect-of-nccn-2015-risk-stratification-on-prognosis-of-patients-with-acute-myeloid-leukemia-after-allogeneic-hematopoietic-stem-cell-transplantation
#9
Y Lu, T Wu, Y L Zhao, X Y Cao, D Y Liu, J P Zhang, M Xiong, J R Zhou, R J Sun, Z J Wei, H Wang, H X Liu, T Wang, C R Tong, S Q Ji, D P Lu
Objective: To analyze the effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Retrospective analysis of 258 patients with AML in CR (186 cases in CR(1), 72 cases in CR(2)) who underwent allogeneic HSCT in our hospital between April 2012 and March 2015 according to NCCN (2015) risk stratification. Of them, 63 cases were classified as low risk, 112 cases intermediate risk and 83 cases high risk...
January 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28219219/-clinical-features-and-prognosis-in-cd10-pre-b-acute-lymphoblastic-leukemia
#10
X Y Gong, Y Wang, B C Liu, H Wei, C L Zhou, D Lin, K Q Liu, S N Wei, B F Gong, G J Zhang, Y T Liu, X L Zhao, Y Li, R X Gu, S W Qiu, Y C Mi, J X Wang
Objective: To analyze the clinical features and prognosis of acute lymphoblastic leukemia patients with immunophenotype of CD10(-)pre-B (CD10(-) pre B-ALL) . Methods: 6 adult cases with CD10(-) pre B-ALL immunophenotypes were analyzed retrospectively, related literatures were reviewed to clarify these kind of patients' clinical features and prognosis. Results: CD10(-) pre B-ALL occurred in 1.5% of ALL, 1.8% of B-ALL and 11.5% of pre B-ALL respectively. All the 6 patients were male with the median age as 33...
January 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28219218/-prognostic-significance-of-early-assessment-of-minimal-residual-disease-in-acute-myeloid-leukemia-with-mutated-npm1-patients
#11
T Zhao, H H Zhu, J Wang, J S Jia, S M Yang, H Jiang, J Lu, H Chen, L P Xu, X H Zhang, B Jiang, G R Ruan, D B Wang, X J Huang, Q Jiang
Objective: To explore prognostic significance of early assessment of minimal residual leukemia (MRD) in adult patients with de novo acute myeloid leukemia (AML) with mutated NPM1. Methods: The response, NPM1 mutated transcript level after induction chemotherapy and the first 2 cycles of consolidation chemotherapy, disease-free survival (DFS) and overall survival (OS) in 137 patients with AML with NPM1 mutations of A, B and D were retrospectively analyzed. Results: Data of 137 patients were collected, 67 were male, the median age was 49 years (16-67 years) , 107 (78...
January 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28218757/allogeneic-stem-cell-transplantation-for-refractory-acute-myeloid-leukemia-in-pediatric-patients-the-uk-experience
#12
P O'Hare, G Lucchini, M Cummins, P Veys, M Potter, S Lawson, A Vora, R Wynn, A Peniket, K Kirkland, R Pearce, J Perry, P J Amrolia
We report outcomes for 44 children who underwent stem cell transplantation (SCT) for refractory AML in the UK between 2000 and 2012. Median age at SCT was 11.5 years. Twenty-three patients had primary refractory and 21 relapsed refractory AML. Refractory disease was confirmed by cytogenetics/molecular genetics in 24 cases. Median follow-up of the whole cohort is 6.8 years (2.1-14.9 years). Thirty patients (68%) achieved a CR following SCT. Transplant-related mortality at 1 year was 18%. Acute GVHD incidence was 52% (grade ⩾III 19%), chronic 7%...
February 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28218567/-allogeneic-hematopoietic-stem-cell-transplantation-in-hungary
#13
Árpád Bátai, Péter Reményi, Marienn Réti, Anikó Barta, László Gopcsa, Lilla Lengyel, Éva Torbágyi, Zoltán Csukly, Éva Karászi, Attila Tordai, Hajnalka Andrikovics, Katalin Balassa, Szabolcs Tasnády, Tamás Masszi
INTRODUCTION AND AIM: The publication summarizes the 2548 stem cell transplantations performed in the period of 1993-2015 in Szent Laszló Hospital, Budapest and provides a detailed discussion of the 425 allogeneic transplantations during 2007-2013. METHOD: The analysis explains the major steps of the evolution of allogeneic stem cell transplantation and compares the results of the unique Hungarian allogeneic center. RESULTS: The significant shift in the transplantation indications from chronic myeloid leukemia to myelodysplastic syndromes and the rising age of the recipients are in line with world wide tendencies...
February 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28218044/leukemia-microvesicles-affect-healthy-hematopoietic-stem-cells
#14
Farnaz Razmkhah, Masoud Soleimani, Davood Mehrabani, Mohammad Hossein Karimi, Sedigheh Amini Kafi-Abad, Mani Ramzi, Mahdiyar Iravani Saadi, Javad Kakoui
Microvesicles are released by different cell types and shuttle mRNAs and microRNAs which have the possibility to transfer genetic information to a target cell and alter its function. Acute myeloid leukemia is a malignant disorder, and leukemic cells occupy all the bone marrow microenvironment. In this study, we investigate the effect of leukemia microvesicles on healthy umbilical cord blood hematopoietic stem cells to find evidence of cell information transferring. Leukemia microvesicles were isolated from acute myeloid leukemia patients and were co-incubated with healthy hematopoietic stem cells...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28218011/asymmetric-dimethylarginine-in-the-assessment-of-febrile-neutropenia-in-hematological-patients
#15
Marika Lappalainen, Sari Hämäläinen, Auni Juutilainen, Irma Koivula, Kari Pulkki, Esa Jantunen
Asymmetric dimethylarginine (ADMA) has been recognized as an independent prognostic factor for sepsis mortality in intensive care units. No data are available on kinetics or prognostic value of ADMA in hematological patients. We evaluated the ability of ADMA to act as a predictor for complicated course of febrile neutropenia, defined as bacteremia and/or septic shock in adult hematological patients receiving intensive chemotherapy. This prospective study included 87 adult hematological patients with febrile neutropenia after an intensive chemotherapy for acute myeloid leukemia (AML) or after an autologous stem cell transplantation (ASCT)...
April 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28217708/aberrant-rna-splicing-and-mutations-in-spliceosome-complex-in-acute-myeloid-leukemia
#16
COMMENT
Jianbiao Zhou, Wee-Joo Chng
The spliceosome, the cellular splicing machinery, regulates RNA splicing of messenger RNA precursors (pre-mRNAs) into maturation of protein coding RNAs. Recurrent mutations and copy number changes in genes encoding spliceosomal proteins and splicing regulatory factors have tumor promoting or suppressive functions in hematological malignancies, as well as some other cancers. Leukemia stem cell (LSC) populations, although rare, are essential contributors of treatment failure and relapse. Recent researches have provided the compelling evidence that link the erratic spicing activity to the LSC phenotype in acute myeloid leukemia (AML)...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28216566/phenotypic-and-functional-alterations-of-hematopoietic-stem-and-progenitor-cells-in-an-in-vitro-leukemia-induced-microenvironment
#17
Jean-Paul Vernot, Ximena Bonilla, Viviana Rodriguez-Pardo, Natalia-Del Pilar Vanegas
An understanding of the cell interactions occurring in the leukemic microenvironment and their functional consequences for the different cell players has therapeutic relevance. By co-culturing mesenchymal stem cells (MSC) with the REH acute lymphocytic leukemia (ALL) cell line, we have established an in vitro leukemic niche for the functional evaluation of hematopoietic stem/progenitor cells (HSPC, CD34+ cells). We showed that the normal homeostatic control exerted by the MSC over the HSPC is considerably lost in this leukemic microenvironment: HSPC increased their proliferation rate and adhesion to MSC...
February 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28215825/stage-specific-human-induced-pluripotent-stem-cells-map-the-progression-of-myeloid-transformation-to-transplantable-leukemia
#18
Andriana G Kotini, Chan-Jung Chang, Arthur Chow, Han Yuan, Tzu-Chieh Ho, Tiansu Wang, Shailee Vora, Alexander Solovyov, Chrystel Husser, Malgorzata Olszewska, Julie Teruya-Feldstein, Deepak Perumal, Virginia M Klimek, Alexandros Spyridonidis, Raajit K Rampal, Lewis Silverman, E Premkumar Reddy, Elli Papaemmanuil, Samir Parekh, Benjamin D Greenbaum, Christina S Leslie, Michael G Kharas, Eirini P Papapetrou
Myeloid malignancy is increasingly viewed as a disease spectrum, comprising hematopoietic disorders that extend across a phenotypic continuum ranging from clonal hematopoiesis to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this study, we derived a collection of induced pluripotent stem cell (iPSC) lines capturing a range of disease stages encompassing preleukemia, low-risk MDS, high-risk MDS, and secondary AML. Upon their differentiation, we found hematopoietic phenotypes of graded severity and/or stage specificity that together delineate a phenotypic roadmap of disease progression culminating in serially transplantable leukemia...
February 13, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28215704/cpg-island-hypermethylation-mediated-by-dnmt3a-is-a-consequence-of-aml-progression
#19
David H Spencer, David A Russler-Germain, Shamika Ketkar, Nichole M Helton, Tamara L Lamprecht, Robert S Fulton, Catrina C Fronick, Michelle O'Laughlin, Sharon E Heath, Marwan Shinawi, Peter Westervelt, Jacqueline E Payton, Lukas D Wartman, John S Welch, Richard K Wilson, Matthew J Walter, Daniel C Link, John F DiPersio, Timothy J Ley
DNMT3A mutations occur in ∼25% of acute myeloid leukemia (AML) patients. The most common mutation, DNMT3A(R882H), has dominant negative activity that reduces DNA methylation activity by ∼80% in vitro. To understand the contribution of DNMT3A-dependent methylation to leukemogenesis, we performed whole-genome bisulfite sequencing of primary leukemic and non-leukemic cells in patients with or without DNMT3A(R882) mutations. Non-leukemic hematopoietic cells with DNMT3A(R882H) displayed focal methylation loss, suggesting that hypomethylation antedates AML...
February 13, 2017: Cell
https://www.readbyqxmd.com/read/28215056/an-analysis-of-blood-utilization-for-stem-cell-transplant-patients-in-a-tertiary-care-hospital
#20
Natasha Ali
Background and Objective: Haematopoietic stem cell transplant is a potentially curative treatment option in various benign and malignant haematological diseases. Patients undergoing stem cell transplant procedure require blood transfusion on a daily basis. Currently, there is paucity of data from developing countries on transfusion practices. This audit was undertaken to determine the consumption of packed red blood cells (PRBCs) transfusion in the bone marrow transplant unit of the Aga Khan University Hospital...
February 28, 2017: International Journal of Stem Cells
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