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Hematopoietic diseases

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https://www.readbyqxmd.com/read/28338506/a-preliminary-report-radical-surgery-and-stem-cell-transplantation-for-the-treatment-of-patients-with-pancreatic-cancer
#1
Brigitta Omazic, Burcu Ayoglu, Matthias Löhr, Ralf Segersvärd, Caroline Verbeke, Isabelle Magalhaes, Zuzana Potacova, Jonas Mattsson, Alexei Terman, Sam Ghazi, Nils Albiin, Nikolaos Kartalis, Peter Nilsson, Thomas Poiret, Liu Zhenjiang, Rainer Heuchel, Jochen M Schwenk, Johan Permert, Markus J Maeurer, Olle Ringden
We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A*01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT...
March 23, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28337888/decitabine-treatment-for-acute-myeloid-leukemia-relapse-after-allogeneic-hematopoietic-stem-cell-transplantation
#2
X L Liu, X Zhao, C Wang, S J Gao, Y H Tan
Therapeutic options for patients with relapse of acute myeloid leukemia (AML) after allo-SCT are limited. Here, we present a case of a 49-year female with AML who underwent myeloablative allo-SCT from a matched sibling donor. Seven months after transplantation she developed cGVHD and suffered from extramedullary plus concurrent medullary relapse. The presence of CNS extramedullary disease is unique. Our patient was treated with decetabine. After one cycle the patient achieved complete remission and full donor chimerism without severe side effects or the occurrence of GVHD...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28336558/remnant-cholesterol-elicits-arterial-wall-inflammation-and-a-multilevel-cellular-immune-response-in-humans
#3
Sophie J Bernelot Moens, Simone L Verweij, Johan G Schnitzler, Lotte C A Stiekema, Merijn Bos, Anne Langsted, Carlijn Kuijk, Siroon Bekkering, Carlijn Voermans, Hein J Verberne, Børge G Nordestgaard, Erik S G Stroes, Jeffrey Kroon
OBJECTIVE: Mendelian randomization studies revealed a causal role for remnant cholesterol in cardiovascular disease. Remnant particles accumulate in the arterial wall, potentially propagating local and systemic inflammation. We evaluated the impact of remnant cholesterol on arterial wall inflammation, circulating monocytes, and bone marrow in patients with familial dysbetalipoproteinemia (FD). APPROACH AND RESULTS: Arterial wall inflammation and bone marrow activity were measured using (18)F-FDG PET/CT...
March 23, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28335858/netting-novel-regulators-of-hematopoiesis-and-hematologic-malignancies-in-zebrafish
#4
Wanda Kwan, Trista E North
Zebrafish are one of the preeminent model systems for the study of blood development (hematopoiesis), hematopoietic stem and progenitor cell (HSPC) biology, and hematopathology. The zebrafish hematopoietic system shares strong similarities in functional populations, genetic regulators, and niche interactions with its mammalian counterparts. These evolutionarily conserved characteristics, together with emerging technologies in live imaging, compound screening, and genetic manipulation, have been employed to successfully identify and interrogate novel regulatory mechanisms and molecular pathways that guide hematopoiesis...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28333839/evidence-for-increased-response-to-induced-endoplasmic-reticulum-stress-in-myeloid-cells-in-acquired-aplastic-anemia
#5
Alpa Sidhu, Michael U Callaghan, Manisha S Gadgeel, Steven A Buck, Andrew M Fribley, Süreyya Savaşan
Autoimmune response targeting the hematopoietic stem cells highlights the current understanding of acquired aplastic anemia (AAA) pathogenesis. Upregulation of the unfolded protein response is the cell's rejoinder to a variety of stresses, which either result in restoring homeostasis or cell death by increased expression of the transcription factor C/EBP homologous protein. We hypothesized that there is an inherent increased sensitivity to various cellular stressors, including the ones that target endoplasmic reticulum (ER) in AAA leading to a decreased proliferation and potentially contributing to susceptibility to autologous cytotoxicity...
April 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28333712/disseminated-lichtheimia-ramosa-infection-after-hematopoietic-stem-cell-transplantation-in-a-child-with-chronic-granulomatous-disease
#6
Michael Winstead, John Ozolek, Andrew Nowalk, John Williams, Mark Vander Lugt, Philana Lin
Mucormycosis is uncommon in patients with chronic granulomatous disease (CGD). We report a 7-year-old boy with X-linked CGD and absent oxidative burst who developed fatal Lichtheimia ramosa infection with fungal thrombosis of the kidneys, spleen, and other organs following hematopoietic stem cell transplantation (HSCT). Lichtheimia infection is rarely reported in patients with CGD and could be related to iatrogenic immunosuppression.
March 22, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28333416/severe-transplant-associated-thrombotic-microangiopathy-in-patients-with-hemoglobinopathies
#7
Ghada A Abusin, Rolla Abu-Arja, Rajinder P S Bajwa, Edwin M Horwitz, Jeffery J Auletta, Hemalatha G Rangarajan
Incidence and severity of transplant-associated thrombotic microangiopathy (TA-TMA) in patients with hemoglobinopathies receiving hematopoietic cell transplant is unknown. We report the outcomes for two patients with TA-TMA who received eculizumab. A 2.5-year-old male with sickle cell disease developed TA-TMA-associated pericardial tamponade, severe hypertension, and acute kidney injury 2 months after transplant. A 7-year-old female with β-thalassemia major developed TA-TMA-related acute kidney injury, severe hypertension, and seizures at 6 months after transplant...
March 23, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28332231/development-of-humanized-mice-in-the-age-of-genome-editing
#8
Vishnu Hosur, Benjamin E Low, Cindy Avery, Leonard D Shultz, Michael V Wiles
Mice are the most commonly used model organisms to study human disease. Many genetic human diseases can be recapitulated by modifying the mouse genome, which permits testing of existing and novel therapeutics, including combinatorial therapeutics, without putting humans at risk. Specifically, the development of "humanized" mice, i.e., severely immunodeficient mice engrafted with functional human hematopoietic and immune cells and tissues, has revolutionized our ability to study and model human diseases in preclinical in vivo systems...
March 22, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28331127/the-impact-of-a-humanized-ccr4-antibody-mogamulizumab-on-patients-with-aggressive-type-adult-t-cell-leukemia-lymphoma-treated-with-allogeneic-hematopoietic-stem-cell-transplantation
#9
Noriaki Kawano, Takuro Kuriyama, Shuro Yoshida, Sayaka Kawano, Yoshihisa Yamano, Kousuke Marutsuka, Seiichirou Minato, Kiyoshi Yamashita, Hidenobu Ochiai, Kazuya Shimoda, Fumihiko Ishikawa, Ikuo Kikuchi
Although a humanized CCR4 antibody (mogamulizumab) was reported to be effective for refractory adult T-cell leukemia-lymphoma (ATL), several reports regarding the use of mogamulizumab before allo-hematopoietic stem cell transplantation (HSCT) strongly indicated a high incidence of severe acute graft-versus-host-disease (GVHD) and treatment-related mortality (TRM). We retrospectively analyzed nine aggressive-type ATL patients who underwent allo-HSCT at a single institution in Miyazaki from 2006.1.1 to 2015.7...
2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/28331056/monitoring-of-childhood-all-using-bcr-abl1-genomic-breakpoints-identifies-a-subgroup-with-cml-like-biology
#10
Lenka Hovorkova, Marketa Zaliova, Nicola C Venn, Kirsten Bleckmann, Marie Trkova, Eliska Potuckova, Martina Vaskova, Jana Linhartova, Katerina Machova Polakova, Eva Fronkova, Walter Muskovic, Jodie E Giles, Peter J Shaw, Gunnar Cario, Rosemary Sutton, Jan Stary, Jan Trka, Jan Zuna
We used the genomic breakpoint between BCR and ABL1 genes for the DNA-based monitoring of minimal residual disease (MRD) in 48 patients with childhood acute lymphoblastic leukemia (ALL). Comparing the results with standard MRD monitoring based on immunoglobulin/T-cell receptor (Ig/TCR) gene rearrangements and with quantification of IKZF1 deletion, we observed very good correlation for the methods in a majority of patients; however, over 20% of children (25% [8/32] with minor and 12.5% [1/8] with Major-BCR-ABL1 variants in the consecutive cohorts) had significantly (>1 log) higher levels of BCR-ABL1 fusion than Ig/TCR rearrangements and/or IKZF1 deletion...
March 22, 2017: Blood
https://www.readbyqxmd.com/read/28331055/reticular-dysgenesis-international-survey-on-clinical-presentation-transplantation-and-outcome
#11
Manfred Hoenig, Chantal Lagresle-Peyrou, Ulrich Pannicke, Luigi D Notarangelo, Fulvio Porta, Andrew R Gennery, Mary Slatter, Morton J Cowan, Polina Stepensky, Hamoud Al-Mousa, Daifulah Al-Zahrani, Sung-Yun Pai, Waleed Al Herz, Hubert B Gaspar, Paul Veys, Koichi Oshima, Kohsuke Imai, Hiromasa Yabe, Lenora M Noroski, Nico M Wulffraat, Karl-Walter Sykora, Pere Soler-Palacin, Hideki Muramatsu, Mariam Al Hilali, Despina Moshous, Klaus-Michael Debatin, Catharina Schuetz, Eva-Maria Jacobsen, Ansgar S Schulz, Klaus Schwarz, Alain Fischer, Wilhelm Friedrich, Marina Cavazzana
Reticular Dysgenesis (RD) is a rare congenital disorder defined clinically by the combination of severe combined immunodeficiency (SCID), agranulocytosis and sensorineural deafness. Mutations in the gene encoding Adenylate Kinase 2 (AK2) were identified to cause the disorder. Hematopoietic stem cell transplantation (HSCT) is the only option to cure this otherwise fatal disease. Retrospective data on clinical presentation, genetics and outcome of HSCT were collected from centers in Europe, Asia and North America for a total of 32 patients born between 1982 and 2011...
March 22, 2017: Blood
https://www.readbyqxmd.com/read/28329410/long-term-outcome-after-a-treosulfan-based-conditioning-regimen-for-patients-with-acute-myeloid-leukemia-a-report-from-the-acute-leukemia-working-party-of-the-european-society-for-blood-and-marrow-transplantation
#12
Arnon Nagler, Myriam Labopin, Dietrich Beelen, Fabio Ciceri, Liisa Volin, Avichai Shimoni, Roberto Foá, Noel Milpied, Jacopo Peccatori, Emmanuelle Polge, Audrey Mailhol, Mohamad Mohty, Bipin N Savani
BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for patients with acute myeloid leukemia (AML). However, post-HCT relapse and regimen-related toxicity remain significant barriers to long-term survival. In recent years, new conditioning regimens have been explored to improve transplantation outcomes in patients with AML. Treosulfan combines a potent immunosuppressive and antileukemic effect with a low toxicity profile. METHODS: To investigate the role of treosulfan-based conditioning, the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party performed a registry analysis of 520 adult patients with AML who received treosulfan-based conditioning and underwent HCT between 2000 and 2012, including 225 patients in first complete remission, 107 in second or later complete remission, and 188 with active/advanced disease 188 (88 with primary refractory disease)...
March 22, 2017: Cancer
https://www.readbyqxmd.com/read/28329354/clinical-significance-of-human-coronavirus-in-bronchoalveolar-lavage-samples-from-hematopoietic-cell-transplantation-recipients-and-patients-with-hematologic-malignancies
#13
Chikara Ogimi, Alpana A Waghmare, Jane M Kuypers, Hu Xie, Cecilia C Yeung, Wendy M Leisenring, Sachiko Seo, Su-Mi Choi, Keith R Jerome, Janet A Englund, Michael Boeckh
Background: The possible role of human coronaviruses (HCoV) in lower respiratory tract disease (LRTD) in hematopoietic cell transplant (HCT) recipients and patients with hematologic malignancies (HM) has not been well studied. Methods: We conducted a retrospective review of HCT/HM patients with HCoV detected in bronchoalveolar lavage (BAL). HCoV strains were identified in BAL samples using strain-specific PCR. Mortality rates were compared among HCT recipients with LRTD caused by HCoV, respiratory syncytial virus (RSV), influenza or parainfluenza virus (PIV) by multivariable Cox regression analysis...
February 17, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28328837/atypical-presentation-of-paroxysmal-nocturnal-hemoglobinuria-treated-by-eculizumab-a-case-report
#14
Anne Quinquenel, Quentin Maestraggi, Carinne Lecoq-Lafon, Peffault de Latour Régis, Alain Delmer, Amélie Servettaz
RATIONALE: Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant acquired hematopoietic stem cell disease, which can be revealed by hemolytic anemia, thromboembolism, or bonemarrow failure. Thrombosis can occur at any site, but coronary thrombosis is extremely rare. Controlled trials have demonstrated that eculizimab, an inhibitor of the terminal complement cascade, was able to reduce both hemolysis and thrombosis, but its efficacy in cases of PNH with coronary thrombosis is unknown...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28328098/plasma-exchange-successfully-treated-macrophage-activation-syndrome-in-rheumatoid-factor-positive-polyarticular-juvenile-idiopathic-arthritis-with-combined-pneumonia
#15
Lianjie Shi, Fanlei Hu, Chuanhui Xu, Huaqun Zhu, Di Qie, Chuanjie Yuan, Yuhong Tao, Hanmin Liu
Macrophage activation syndrome (MAS) is one of the serious complications associated with rheumatic diseases, especially systemic juvenile idiopathic arthritis (sJIA). Here we describe a 9-year-old girl with rheumatoid factor (RF)-positive polyarticular JIA, not sJIA, combined with pneumonia who was successfully treated by plasma exchange. She was diagnosed with RF-positive polyarticular JIA based on positive RF and multiple joint swelling and tenderness 3 years ago. She was admitted in our hospital with myalgia for 2 days and a high fever for half a day...
March 22, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28326848/autologous-hematopoietic-stem-cells-for-refractory-crohn-s-disease
#16
C A DiNicola, A Zand, D W Hommes
Autologous hematopoietic stem cells are gaining ground as an effective and safe treatment for treating severe refractory Crohn's disease (CD). Autologous hematopoietic stem cell therapy (AHSCT) induces resetting of the immune system by de novo regeneration of T-cell repertoire and repopulation of epithelial cells by bone-marrow derived cells to help patients achieve clinical and endoscopic remission. Areas covered: Herein, the authors discuss the use of AHSCT in treating patients with CD. Improvements in disease activity have been seen in patients with severe autoimmune disease and patients with severe CD who underwent AHSCT for a concomitant malignant hematological disease...
March 22, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28326208/a-child-as-a-donor-for-hematopoietic-stem-cell-transplantation-bioethical-justification-a-case-study-on-sickle-cell-disease
#17
Andrea Z Pereira, Ricardo Hellman, Nelson Hamerschlak, Andrea Kondo, Polianna Mara Rodrigues de Souza, Wilson Leite Pedreira, Luiz Fernando Alves Lima Mantovani, Eduardo Juan Troster, Henrique Grunspun, Marco Aurélio Scarpinella Bueno
Hematopoietic stem cell transplantation (HSCT) is an important treatment option for children with severe and refractory sickle cell disease (SCD) with debilitating clinical complications. HSCT with cells from the bone marrow of a HLA-identical sibling used in SCD has a low mortality risk, high cure rate, and high event-free survival rate after a median follow-up of 5-6 years. However, matched donors are found in only about 20% of the patients. A boy aged 8 years with SCD had a sister, <2 years old, a fully compatible donor...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28325354/solitary-plasmacytoma-associated-with-epstein-barr-virus-a-clinicopathologic-cytogenetic-study-and-literature-review
#18
Jiaqi Yan, Jianchao Wang, Wenyan Zhang, Min Chen, Jie Chen, Weiping Liu
Solitary plasmacytoma (SP) is an uncommon, indolent tumor of plasma cell neoplasms that presents as a mass lesion in extramedullary sites. Evidence of Epstein-Barr virus (EBV) infection is frequently associated with various lymphatic and hematopoietic malignancies but is relatively rare in SP. Moreover, it is essential to distinguish EBV-positive plasmacytoma from plasmablastic lymphoma. In this study, we found 4 EBV-encoded RNA (EBER)-positive patients among 46 consecutive immunocompetent patients of SP and compared the clinicopathologic features of these patients with those of the EBER-negative cohort...
April 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28325300/one-step-biallelic-and-scarless-correction-of-a-%C3%AE-thalassemia-mutation-in-patient-specific-ipscs-without-drug-selection
#19
Yali Liu, Yi Yang, Xiangjin Kang, Bin Lin, Qian Yu, Bing Song, Ge Gao, Yaoyong Chen, Xiaofang Sun, Xiaoping Li, Lei Bu, Yong Fan
Monogenic disorders (MGDs), which are caused by single gene mutations, have a serious effect on human health. Among these, β-thalassemia (β-thal) represents one of the most common hereditary hematological diseases caused by mutations in the human hemoglobin β (HBB) gene. The technologies of induced pluripotent stem cells (iPSCs) and genetic correction provide insights into the treatments for MGDs, including β-thal. However, traditional approaches for correcting mutations have a low efficiency and leave a residual footprint, which leads to some safety concerns in clinical applications...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28325276/limiting-thymic-precursor-supply-increases-the-risk-of-lymphoid-malignancy-in-murine-x-linked-severe-combined-immunodeficiency
#20
Samantha L Ginn, Claus V Hallwirth, Sophia H Y Liao, Erdahl T Teber, Jonathan W Arthur, Jianmin Wu, Hong Ching Lee, Szun S Tay, Min Hu, Roger R Reddel, Matthew P McCormack, Adrian J Thrasher, Marina Cavazzana, Stephen I Alexander, Ian E Alexander
In early gene therapy trials for SCID-X1, using γ-retroviral vectors, T cell leukemias developed in a subset of patients secondary to insertional proto-oncogene activation. In contrast, we have reported development of T cell leukemias in SCID-X1 mice following lentivirus-mediated gene therapy independent of insertional mutagenesis. A distinguishing feature in our study was that only a proportion of transplanted γc-deficient progenitors were transduced and therefore competent for reconstitution. We hypothesized that reconstitution of SCID-X1 mice with limiting numbers of hematopoietic progenitors might be a risk factor for lymphoid malignancy...
March 17, 2017: Molecular Therapy. Nucleic Acids
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