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neutrophilic leukemia

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https://www.readbyqxmd.com/read/28938529/defining-a-therapeutic-window-for-kinase-inhibitors-in-leukemia-to-avoid-neutropenia
#1
Kate McArthur, Akshay A D'Cruz, David Segal, Kurt Lackovic, Andrew F Wilks, Joanne A O'Donnell, Cameron J Nowell, Motti Gerlic, David C S Huang, Christopher J Burns, Ben A Croker
Neutropenia represents one of the major dose-limiting toxicities of many current cancer therapies. To circumvent the off-target effects of cytotoxic chemotherapeutics, kinase inhibitors are increasingly being used as an adjunct therapy to target leukemia. In this study, we conducted a screen of leukemic cell lines in parallel with primary neutrophils to identify kinase inhibitors with the capacity to induce apoptosis of myeloid and lymphoid cell lines whilst sparing primary mouse and human neutrophils. We have utilized a high-throughput live cell imaging platform to demonstrate that cytotoxic drugs have limited effects on neutrophil viability but are toxic to hematopoietic progenitor cells, with the exception of the topoisomerase I inhibitor SN-38...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28927137/atypical-chronic-myeloid-leukemia-with-isochromosome-x-p10-a-case-report
#2
Masahide Yamamoto, Sayaka Suzuki, Jun-Ichi Mukae, Keisuke Tanaka, Ken Watanabe, Gaku Oshikawa, Tetsuya Fukuda, Naomi Murakami, Osamu Miura
Atypical chronic myeloid leukemia (aCML) is a rare subtype of myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Although recurrent chromosomal and genetic abnormalities are frequently observed in aCML, none are specific to this type of leukemia. The present study reported a case of aCML associated with i(X)(p10), a rare recurrent chromosomal abnormality of hematological malignancy. A 40-year-old female was referred to the Tokyo Medical and Dental University Hospital (Tokyo, Japan) due to slight leukocytosis and anemia...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28910431/hla-mismatched-microtransplant-in-older-patients-newly-diagnosed-with-acute-myeloid-leukemia-results-from-the-microtransplantation-interest-group
#3
Mei Guo, Nelson J Chao, Jian-Yong Li, David A Rizzieri, Qi-Yun Sun, Ann Mohrbacher, Elizabeth F Krakow, Wan-Jun Sun, Xu-Liang Shen, Xin-Rong Zhan, De-Pei Wu, Li Liu, Juan Wang, Min Zhou, Lin-Hua Yang, Yang-Yi Bao, Zheng Dong, Bo Cai, Kai-Xun Hu, Chang-Lin Yu, Jian-Hui Qiao, Hong-Li Zuo, Ya-Jing Huang, Anthony D Sung, Jun-Xiao Qiao, Zhi-Qing Liu, Tie-Qiang Liu, Bo Yao, Hong-Xia Zhao, Si-Xuan Qian, Wei-Wei Liu, Rafael Forés, Rafael F Duarte, Hui-Sheng Ai
Importance: The outcome of older patients with acute myeloid leukemia (AML) remains unsatisfactory. Recent studies have shown that HLA-mismatched microtransplant could improve outcomes in such patients. Objective: To evaluate outcomes in different age groups among older patients with newly diagnosed AML who receive HLA-mismatched microtransplant. Design, Setting, and Participants: This multicenter clinical study included 185 patients with de novo AML at 12 centers in China, the United States, and Spain in the Microtransplantation Interest Group...
September 14, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28901479/interaction-with-neutrophils-promotes-gastric-cancer-cell-migration-and-invasion-by-inducing-epithelial-mesenchymal-transition
#4
Wen Zhang, Jianmei Gu, Jingyan Chen, Peng Zhang, Runbi Ji, Hui Qian, Wenrong Xu, Xu Zhang
Emerging evidence has revealed that neutrophils have phenotypic and functional plasticity. Neutrophils could be polarized towards a pro-tumor phenotype by tumor-derived factors. In the present study, we investigated the role of the interaction with neutrophils on the functions of gastric cancer cells in vitro. Human promyelocytic leukemia HL-60 cells were induced to differentiate into neutrophil-like cells (HL-60N) using dimethyl sulfoxide (DMSO). Human gastric cancer cells were co-cultured with HL-60N cells or treated with the conditioned medium (CM) of cancer-activated HL-60N cells...
September 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28871936/xanthoma-like-skin-changes-in-an-elderly-woman-with-a-normal-lipid-profile
#5
Piotr Nockowski, Zdzisław Woźniak, Adam Reich, Joanna Maj
Dear Editor, An 83-year-old woman developed yellow-brownish infiltrates, nodules, and tumors mimicking xanthomas, mostly involving the periorbital and chest area within three months (Figure 1). She had no abnormalities in serum cholesterol or triglycerides levels. A detailed laboratory analysis revealed the presence of mild monoclonal gammopathy with a presence of immunoglobulin G (IgG) kappa light chains; however, according to hematologist consultation, it did not require medical intervention. Imaging assessment and ultrasound examination did not show any specific involvement of internal organs...
July 2017: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/28864336/analysis-of-transfusion-related-acute-lung-injury-and-possible-transfusion-related-acute-lung-injury-reported-to-the-french-hemovigilance-network-from-2007-to-2013
#6
REVIEW
Georges Andreu, Karim Boudjedir, Jean-Yves Muller, Elodie Pouchol, Yves Ozier, Guillaume Fevre, Chantal Gautreau, Jean-François Quaranta, Christian Drouet, Claire Rieux, Paul-Michel Mertes, Benoit Clavier, Monique Carlier, Imad Sandid
Using the French Hemovigilance Network database from 2007 to 2013, we provide information on demographics, incidence, and risk factors of reported transfusion-related acute lung injury (TRALI) and possible TRALI, analyze TRALI mitigation efforts for fresh frozen plasma and platelet concentrates, and consider the impact of platelet additive solutions on TRALI incidence. We applied the Toronto consensus conference definitions for TRALI and possible TRALI. Two TRALI subgroups were considered: "antibody positive" when a donor has human leukocyte antigen (class I or II) and/or human neutrophil antigen antibodies and the recipient has cognate antigen, and "antibody negative" when immunological investigation is negative or not done...
July 15, 2017: Transfusion Medicine Reviews
https://www.readbyqxmd.com/read/28863210/alternatively-spliced-mefv-transcript-lacking-exon-2-and-its-protein-isoform-pyrin-2d-implies-an-epigenetic-regulation-of-the-gene-in-inflammatory-cell-culture-models
#7
Gokce Celikyapi Erdem, Sule Erdemir, Irem Abaci, Asli K Kirectepe Aydin, Elif Everest, Eda Tahir Turanli
The function of gene body DNA methylation in alternative splicing, and its relation to disease pathogenesis is not fully elucidated. The gene for familial Mediterranean fever (MEFV) encodes the pyrin protein and contains a 998 bp CpG island, covering the second exon, which is differentially methylated in FMF patients compared to healthy controls. Our further observation of increased exon 2-spliced MEFV transcript in leukocytes of FMF patients provoked us to test the role of exon methylation in alternative splicing using inflammatory cell culture models...
July 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28846072/mice-expressing-krasg12d-in-hematopoietic-multipotent-progenitor-cells-develop-neonatal-myeloid-leukemia
#8
Stefan P Tarnawsky, Rebecca J Chan, Mervin C Yoder
Juvenile myelomonocytic leukemia (JMML) is a pediatric myeloproliferative neoplasm that bears distinct characteristics associated with abnormal fetal development. JMML has been extensively modeled in mice expressing the oncogenic KrasG12D mutation. However, these models have struggled to recapitulate the defining features of JMML due to in utero lethality, nonhematopoietic expression, and the pervasive emergence of T cell acute lymphoblastic leukemia. Here, we have developed a model of JMML using mice that express KrasG12D in multipotent progenitor cells (Flt3Cre+ KrasG12D mice)...
August 28, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28841879/an-integrative-multi-lineage-model-of-variation-in-leukopoiesis-and-acute-myelogenous-leukemia
#9
Joyatee M Sarker, Serena M Pearce, Robert P Nelson, Tamara L Kinzer-Ursem, David M Umulis, Ann E Rundell
BACKGROUND: Acute myelogenous leukemia (AML) progresses uniquely in each patient. However, patients are typically treated with the same types of chemotherapy, despite biological differences that lead to differential responses to treatment. RESULTS: Here we present a multi-lineage multi-compartment model of the hematopoietic system that captures patient-to-patient variation in both the concentration and rates of change of hematopoietic cell populations. By constraining the model against clinical hematopoietic cell recovery data derived from patients who have received induction chemotherapy, we identified trends for parameters that must be met by the model; for example, the mitosis rates and the probability of self-renewal of progenitor cells are inversely related...
August 25, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28804660/large-granular-lymphocytic-leukemia-a-report-of-response-to-rituximab
#10
Uroosa Ibrahim, Sara Parylo, Shiksha Kedia, Shafinaz Hussein, Jean Paul Atallah
Large granular lymphocytic (LGL) leukemia is a rare form of low grade leukemia characterized by large cytotoxic T cells or natural killer cells on morphological examination. Immunosuppressive therapy is employed as first-line therapy. Treatment options in refractory cases include the anti-CD52 antibody alemtuzumab and purine analogues. We report a rare case that responded to the anti-CD20 monoclonal antibody rituximab. A 77-year-old female presented with complaints of fatigue, fever, and chills of 3 months' duration...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28803258/the-impact-of-antimicrobial-prophylaxis-in-morbidity-and-infections-during-azacitidine-treatment
#11
Natalia Lorenzana, Laura Francisca Avila, Sara Alonso, Enrique Colado, Teresa Bernal
The clinical consequences of the infectious events in patients receiving azacitidine are poorly documented. Likewise, the role of primary antimicrobial prophylaxis is unknown. In this retrospective, single-center study, we compare the impact of prophylaxis on the incidence of infection and morbidity in all consecutive higher-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients, during the first 4 azacitidine cycles. Seventy-six patients, corresponding to 283 azacitidine cycles, were studied...
August 13, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28771804/palmar-eccrine-hidradenitis-secondary-to-trauma-from-computer-gaming-in-an-adolescent-after-bone-marrow-transplantation
#12
Lynette Ying Lee, Mark Jean-Aan Koh
A 14-year-old boy who had undergone a matched sibling bone marrow transplant for acute lymphoblastic leukemia presented with painful nodules on his palms after prolonged gaming on his computer and mobile phone. Histology showed a neutrophilic inflammatory infiltrate surrounding the acrosyringium and eccrine sweat coils in the deep dermis. The lesions resolved spontaneously with conservative management.
August 2, 2017: Pediatric Dermatology
https://www.readbyqxmd.com/read/28762112/targeted-next-generation-sequencing-identifies-clinically-relevant-mutations-in-patients-with-chronic-neutrophilic-leukemia-at-diagnosis-and-blast-crisis
#13
S E Langabeer, K Haslam, J Kelly, J Quinn, R Morrell, E Conneally
PURPOSE: Chronic neutrophilic leukemia is a rare form of myeloproliferative neoplasm characterized by mature neutrophil hyperleukocytosis. The majority of patients harbor somatic mutations of CSF3R gene and are potentially amenable to targeted therapy with JAK inhibitors. The incidence and clinical significance of additional mutations requires clarification. MATERIALS AND METHODS: A next-generation sequencing approach for myeloid malignancy-associated mutations was applied to diagnostic and matched blast crisis samples from four chronic neutrophilic leukemia patients...
July 31, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28748605/management-of-chemotherapy-induced-febrile-neutropenia-in-pediatric-oncology-patients-a-north-american-survey-of-pediatric-hematology-oncology-and-pediatric-infectious-disease-physicians
#14
Rochelle R Maxwell, Dana Egan-Sherry, Jonathan B Gill, Michael E Roth
BACKGROUND: Chemotherapy-induced febrile neutropenia (FN) is traditionally managed with hospital admission for parenteral antibiotics until neutropenia resolves. Recent studies have explored risk stratification and the safety of managing "low-risk" patients as outpatients. Few studies have directly assessed pediatric provider preferences for managing FN. PROCEDURE: We conducted a survey of practicing US and Canadian pediatric hematology/oncology (PHO) and pediatric infectious disease (PID) physicians to assess their FN management preferences using case scenarios with varying risk profiles...
July 27, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28744022/granulocyte-colony-stimulating-factor-gcsf-fused-with-fc-domain-produced-from-e-coli-is-less-effective-than-polyethylene-glycol-conjugated-gcsf
#15
Bich Hang Do, Hyo Jeong Kang, Jung-A Song, Minh Tan Nguyen, Sangsu Park, Jiwon Yoo, Anh Ngoc Nguyen, Grace G Kwon, Jaepyeong Jang, Mihee Jang, Sunju Lee, Seoungjun So, Seongrak Sim, Kyung Jin Lee, Mark J Osborn, Han Choe
Human granulocyte colony-stimulating factor (GCSF) is a well-known cytokine for neutropenia treatment. However, daily injections are required due to the short circulating half-life of the protein. To overcome this bottleneck, we fused GCSF with the Fc domain of IgG1 at the C terminus (GCSF-Fc) and with the maltose binding protein (MBP) tag at the N-terminus and expressed it as a soluble protein in the cytoplasm of E. coli. We also conjugated PEG aldehyde to GCSF to make PEG-GCSF. The bioactivities of GCSF-Fc and PEG-GCSF were similar to native GCSF using the mouse M-NFS-60 myelogenous leukemia cell line...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729147/adult-umbilical-cord-blood-transplantation-using-myeloablative-thiotepa-total-body-irradiation-and-fludarabine-conditioning
#16
Sarah Anand, Samantha Thomas, Kelly Corbet, Cristina Gasparetto, Gwynn D Long, Richard Lopez, Ashley K Morris, David A Rizzieri, Keith M Sullivan, Anthony D Sung, Stefanie Sarantopoulos, Nelson J Chao, Mitchell E Horwitz
Treatment-related mortality (TRM) remains elevated in adult patients undergoing umbilical cord blood transplantation (UCBT), including an early rise in TRM suggestive of excessive toxicity associated with the standard myeloablative total body irradiation (TBI), fludarabine, and cyclophosphamide regimen. In an attempt to reduce regimen-related toxicity, we previously studied a modified myeloablative regimen with TBI (1350 cGy) and fludarabine (160 mg/m(2)); TRM was decreased, but neutrophil engraftment was suboptimal...
July 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28718199/the-clec12a-receptor-marks-human-basophils-potential-implications-for-minimal-residual-disease-detection-in-acute-myeloid-leukemia
#17
Marie Toft-Petersen, Anne Stidsholt Roug, Trine Plesner, Lene Ebbesen, Gordon D Brown, Line Nederby
BACKGROUND: The transmembrane receptor C-type lectin domain family 12, member A (CLEC12A) is known to be highly expressed on monocytes and neutrophils and is a reliable leukemia associated marker in acute myeloid leukemia. Consequently, detailed knowledge of the various normal cell types expressing this receptor is essential. We have observed CLEC12A to be expressed on CD45lowSSClowCD14-CD123+ basophils in peripheral blood (PB) and in this study, we aimed at verifying this observation and further delineate the CD45lowSSClowCD14-CD123 + CLEC12A+ subpopulation...
July 17, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28711727/a-chemotherapy-only-regimen-of-busulfan-melphalan-and-fludarabine-and-rabbit-antithymocyte-globulin-followed-by-allogeneic-t-cell-depleted-hematopoietic-stem-cell-transplantations-for-the-treatment-of-myeloid-malignancies
#18
Barbara Spitzer, Ann A Jakubowski, Esperanza B Papadopoulos, Kirsten Fuller, Patrick D Hilden, James W Young, Juliet N Barker, Guenther Koehne, Miguel-Angel Perales, Katharine C Hsu, Marcel R van den Brink, Nancy A Kernan, Susan E Prockop, Andromachi Scaradavou, Hugo Castro-Malaspina, Richard J O'Reilly, Farid Boulad
We sought to develop a myeloablative chemotherapeutic regimen to secure consistent engraftment of T-cell depleted (TCD) hematopoietic stem cell transplantations (HSCT) without the need for total body irradiation, thereby reducing toxicity while maintaining low rates of graft-versus-host disease (GVHD) and without increasing relapse. We investigated the myeloablative combination of busulfan (Bu) and melphalan (Mel), with the immunosuppressive agents fludarabine (Flu) and rabbit antithymocyte globulin (r-ATG) as cytoreduction before a TCD HSCT...
July 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28705776/short-and-medium-term-biological-variation-estimates-of-leukocytes-extended-to-differential-count-and-morphology-structural-parameters-cell-population-data-in-blood-samples-obtained-from-healthy-people
#19
Sabrina Buoro, Anna Carobene, Michela Seghezzi, Barbara Manenti, Aurelio Pacioni, Ferruccio Ceriotti, Cosimo Ottomano, Giuseppe Lippi
BACKGROUND: Recent studies showed that some cell population data (CPD) parameters of neutrophils may be useful for diagnosing myelodysplastic syndromes and sepsis, for the differential diagnosis of acute promyelocytic leukemia, and some CPD parameters of lymphocytes may be a valuable tool for preliminary screening of B cell lymphoproliferative disease. Notwithstanding the knowledge, no information has been made available about their analytical quality specification. This study was aimed to define short- and medium-term biological variation (BV) estimates and reference change value (RCV) of leukocyte count, extended leukocyte differential and CPD...
October 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28691152/reduced-bucy-2-and-g-csf-primed-bone-marrow-associates-with-low-graft-versus-host-disease-and-transplant-related-mortality-in-allogeneic-hsct
#20
Eucario Leon Rodriguez, Monica M Rivera Franco, Sandra I Perez Alvarez
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the ideal treatment for several diseases. However, the morbidity and mortality associated with the procedure might limit its widespread use; therefore, we implemented reduced BUCY2 as conditioning method along with the use of G-CSF-primed bone marrow (G-BM) in order to reduce complications, including graft-versus-host-disease (GVHD), and to improve survival in these patients. An analysis of transplant characteristics, complications, and survival of patients undergoing an allo-HSCT using this conditioning regimen (busulfan 12 mg/kg and cyclophosphamide 80 mg/kg) plus G-BM was performed...
September 2017: Annals of Hematology
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