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https://www.readbyqxmd.com/read/28550450/abcc4-functional-snp-in-the-3-splice-acceptor-site-of-exon-8-g912t-is-associated-with-unfavorable-clinical-outcome-in-children-with-acute-lymphoblastic-leukemia
#1
Hamzeh Mesrian Tanha, Soheila Rahgozar, Marjan Mojtabavi Naeini
OBJECTIVES: ATP-binding cassette subfamily C member 4 (ABCC4) encoding MRP4 protein is involved in pediatric acute lymphoblastic leukemia (ALL) drug resistance. The nonsynonymous single nucleotide polymorphism (SNP) rs2274407 (G912T; K304N) is located in the 3' splice acceptor site of exon 8 of ABCC4 pre-mRNA. The aim of this study was to investigate the prognostic value of rs2274407 in childhood ALL and its possible functional effect on MRP4. METHODS: ABCC4 G912T SNP was genotyped in 145 Iranian Philadelphia-negative (Ph(-)) children with ALL using modified tetra-primer ARMS PCR and evaluated for possible association with 3-year disease-free survival (3DFS)...
May 26, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28549237/haploidentical-allogeneic-hematopoietic-stem-cell-transplantation-compared-to-matched-unrelated-transplantation-for-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#2
Bin Gu, Xiaojin Wu, Guanghua Chen, Xiao Ma, Zhengming Jin, Xiaowen Tang, Yue Han, Chengcheng Fu, Huiying Qiu, Aining Sun, Depei Wu
To investigate the effect of haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), the outcome of 58 patients with Ph+ ALL who received Haplo-HCT (n=42) or matched unrelated donor transplantation (MUD-HCT) (n=16) during the same period were analyzed retrospectively. All patients received a tyrosine kinase inhibitor (TKI)-based regimen before transplantation, and TKI was resumed primarily after transplantation...
May 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28547782/due-to-potential-concerns-of-bias-and-conflicts-of-interest-regulatory-bodies-should-not-do-evaluation-methodology-research-related-to-their-regulatory-missions
#3
Dev P Chakraborty, Robert M Nishikawa, Colin G Orton
One of the major roles of regulatory bodies is to enforce rules and thus maintain standards. They also often do research related to their missions, some of which might be used to establish the standards they are regulating and how they should be evaluated. This has led some to believe that, due to potential concerns of bias and conflicts of interest, regulatory bodies should not do evaluation methodology research related to their regulatory missions. This is the claim that is debated in this month's Point/Counterpoint...
May 26, 2017: Medical Physics
https://www.readbyqxmd.com/read/28528347/discriminative-accuracy-of-physician-and-nurse-predictions-for-survival-and-functional-outcomes-6-months-after-an-icu-admission
#4
Michael E Detsky, Michael O Harhay, Dominique F Bayard, Aaron M Delman, Anna E Buehler, Saida A Kent, Isabella V Ciuffetelli, Elizabeth Cooney, Nicole B Gabler, Sarah J Ratcliffe, Mark E Mikkelsen, Scott D Halpern
Importance: Predictions of long-term survival and functional outcomes influence decision making for critically ill patients, yet little is known regarding their accuracy. Objective: To determine the discriminative accuracy of intensive care unit (ICU) physicians and nurses in predicting 6-month patient mortality and morbidity, including ambulation, toileting, and cognition. Design, Setting, and Participants: Prospective cohort study conducted in 5 ICUs in 3 hospitals in Philadelphia, Pennsylvania, and enrolling patients who spent at least 3 days in the ICU from October 2013 until May 2014 and required mechanical ventilation, vasopressors, or both...
May 21, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28526220/lumbar-puncture-for-all-febrile-infants-29-56-days-old-a-retrospective-cohort-reassessment-study
#5
Richard Scarfone, Ashlee Murray, Payal Gala, Fran Balamuth
OBJECTIVES: To determine the incidence of bacterial meningitis (BM) among all febrile infants 29-56 days old undergoing a lumbar puncture (LP) in the emergency department of a tertiary care children's hospital and the number of low-risk febrile infants with BM to reassess the need for routine LP in these infants. STUDY DESIGN: Retrospective cohort study using a quality improvement registry from July 2007-April 2014. Infants included were 29-56 days old with fever and who had an LP in the emergency department...
May 16, 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/28521421/an-unusual-translocation-t-1-11-q21-q23-in-a-case-of-chronic-myeloid-leukemia-with-a-cryptic-philadelphia-chromosome
#6
Leandro Germán Gutiérrez, María Fernanda Noriega, Alejandro Laudicina, Mariana Quatrin, Raquel María Bengió, Irene Larripa
Chronic myeloid leukemia (CML) is characterized by the translocation t(9;22)(q34;q11) [Philadelphia (Ph) chromosome). Although not frequently occurring, additional chromosome abnormalities (ACAs) can be detected at diagnosis and a number have been associated with an adverse cytogenetic and molecular outcome. The present study reports a case of CML presenting with the translocation t(1;11)(q21;q23) and a cryptic Ph chromosome. The presence of ACAs could generate greater genetic instability, promoting the emergence of further alterations...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28499401/are-general-and-strategic-measures-of-organizational-context-and-leadership-associated-with-knowledge-and-attitudes-toward-evidence-based-practices-in-public-behavioral-health-settings-a-cross-sectional-observational-study
#7
Byron J Powell, David S Mandell, Trevor R Hadley, Ronnie M Rubin, Arthur C Evans, Matthew O Hurford, Rinad S Beidas
BACKGROUND: Examining the role of modifiable barriers and facilitators is a necessary step toward developing effective implementation strategies. This study examines whether both general (organizational culture, organizational climate, and transformational leadership) and strategic (implementation climate and implementation leadership) organizational-level factors predict therapist-level determinants of implementation (knowledge of and attitudes toward evidence-based practices). METHODS: Within the context of a system-wide effort to increase the use of evidence-based practices (EBPs) and recovery-oriented care, we conducted an observational, cross-sectional study of 19 child-serving agencies in the City of Philadelphia, including 23 sites, 130 therapists, 36 supervisors, and 22 executive administrators...
May 12, 2017: Implementation Science: IS
https://www.readbyqxmd.com/read/28494052/association-of-minimal-residual-disease-with-clinical-outcome-in-pediatric-and-adult-acute-lymphoblastic-leukemia-a-meta-analysis
#8
Donald A Berry, Shouhao Zhou, Howard Higley, Lata Mukundan, Shuangshuang Fu, Gregory H Reaman, Brent L Wood, Gary J Kelloff, J Milburn Jessup, Jerald P Radich
Importance: Minimal residual disease (MRD) refers to the presence of disease in cases deemed to be in complete remission by conventional pathologic analysis. Assessing the association of MRD status following induction therapy in patients with acute lymphoblastic leukemia (ALL) with relapse and mortality may improve the efficiency of clinical trials and accelerate drug development. Objective: To quantify the relationships between event-free survival (EFS) and overall survival (OS) with MRD status in pediatric and adult ALL using publications of clinical trials and other databases...
May 11, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28466557/the-bcr-abl1-transcript-type-influences-response-and-outcome-in-philadelphia-chromosome-positive-chronic-myeloid-leukemia-patients-treated-frontline-with-imatinib
#9
Fausto Castagnetti, Gabriele Gugliotta, Massimo Breccia, Alessandra Iurlo, Luciano Levato, Francesco Albano, Paolo Vigneri, Elisabetta Abruzzese, Giuseppe Rossi, Serena Rupoli, Francesco Cavazzini, Bruno Martino, Ester Orlandi, Patrizia Pregno, Mario Annunziata, Emilio Usala, Mario Tiribelli, Simona Sica, Massimiliano Bonifacio, Carmen Fava, Filippo Gherlinzoni, Monica Bocchia, Simona Soverini, Maria Teresa Bochicchio, Michele Cavo, Martinelli Giovanni, Giuseppe Saglio, Fabrizio Pane, Michele Baccarani, Gianantonio Rosti
The most frequent BCR-ABL1 fusion transcripts in chronic myeloid leukemia (CML) are the e13a2 (b2a2) and the e14a2 (b3a2) ones. In the imatinib era few studies addressing the prognostic significance of the BCR-ABL1 transcript type in early chronic phase CML have been published. Overall, these studies suggest that in e14a2 patients the response to imatinib is faster and deeper. To evaluate if the BCR-ABL1 transcript type (e13a2 compared to e14a2) affect the response to imatinib and the clinical outcome in newly diagnosed adult CML patients, 559 patients enrolled in 3 prospective studies (NCT00514488, NCT00510926, observational study CML/023) were analyzed...
May 2, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28461505/suppressors-and-activators-of-jak-stat-signaling-at-diagnosis-and-relapse-of-acute-lymphoblastic-leukemia-in-down-syndrome
#10
Omer Schwartzman, Angela Maria Savino, Michael Gombert, Chiara Palmi, Gunnar Cario, Martin Schrappe, Cornelia Eckert, Arend von Stackelberg, Jin-Yan Huang, Michal Hameiri-Grossman, Smadar Avigad, Geertruy Te Kronnie, Ifat Geron, Yehudit Birger, Avigail Rein, Giulia Zarfati, Ute Fischer, Zohar Mukamel, Martin Stanulla, Andrea Biondi, Giovanni Cazzaniga, Amedeo Vetere, Bridget K Wagner, Zhu Chen, Sai-Juan Chen, Amos Tanay, Arndt Borkhardt, Shai Izraeli
Children with Down syndrome (DS) are prone to development of high-risk B-cell precursor ALL (DS-ALL), which differs genetically from most sporadic pediatric ALLs. Increased expression of cytokine receptor-like factor 2 (CRLF2), the receptor to thymic stromal lymphopoietin (TSLP), characterizes about half of DS-ALLs and also a subgroup of sporadic "Philadelphia-like" ALLs. To understand the pathogenesis of relapsed DS-ALL, we performed integrative genomic analysis of 25 matched diagnosis-remission and -relapse DS-ALLs...
May 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28457753/expression-of-cd25-on-leukemic-stem-cells-in-bcr-abl1-cml-potential-diagnostic-value-and-functional-implications
#11
REVIEW
Irina Sadovnik, Harald Herrmann, Gregor Eisenwort, Katharina Blatt, Gregor Hoermann, Niklas Mueller, Wolfgang R Sperr, Peter Valent
Chronic myeloid leukemia (CML) is a stem cell-derived leukemia in which neoplastic cells exhibit the Philadelphia (Ph) chromosome and the related oncoprotein, BCR-ABL1. The disease is characterized by an accumulation of myeloid precursor cells in the peripheral blood (PB) and bone marrow (BM). A small fraction of neoplastic cells in the CML clone supposedly exhibits self-renewal and thus long-term disease-propagating ability. However, so far, little is known about the phenotype, function, and target expression-profiles of these leukemic stem cells (LSC)...
April 27, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28454362/growth-of-tyrosine-kinase-inhibitor-resistant-philadelphia-positive-acute-lymphoblastic-leukemia-role-of-bone-marrow-stromal-cells
#12
Cheng Zhang, Xi Zhang, Shi-Jie Yang, Xing-Hua Chen
Human bone marrow stromal cells (hBMSCs) may contribute to the growth of tyrosine kinase inhibitor (TKI)-resistant chronic myelogenous leukemia (CML). However, there are certain differences in biology between CML and Philadelphia-positive acute lymphoblastic leukemia (Ph(+) ALL). Little is known about the role and mechanism of hBMSCs on the growth of TKI-resistant Ph(+) ALL. The current study co-cultured hBMSCs with the TKI-resistant SUP-B15. Next, the proliferation of SUP-B15 was detected using a Cell Counting Kit-8...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28445932/high-cftr-expression-in-philadelphia-chromosome-positive-acute-leukemia-protects-and-maintains-continuous-activation-of-bcr-abl-and-related-signaling-pathways-in-combination-with-pp2a
#13
Xi Yang, Tianyou Yan, Yuping Gong, Xuehua Liu, Huaqin Sun, Wenming Xu, Chunsen Wang, Duolan Naren, Yuhuan Zheng
Cystic fibrosis transmembrane conductance regulator (CFTR) is classified as an anion channel transporter of Cl- and HCO3-. Through interactions with its PDZ domain, CFTR is capable of regulating other proteins, such as protein phosphatase 2A (PP2A). The aberrant expression and mutation of CFTR have been observed in several tumor, but not in philadelphia chromosome-positive(Ph+) acute leukemia, including Ph+ B cell acute lymphoblastic leukemia(Ph+ B-ALL) and chronic myelogenous leukemia blast crisis phases (CML-BC)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444644/ponatinib-in-japanese-patients-with-philadelphia-chromosome-positive-leukemia-a-phase-1-2-study
#14
Arinobu Tojo, Taiichi Kyo, Kazuhito Yamamoto, Hirohisa Nakamae, Naoto Takahashi, Yukio Kobayashi, Tetsuzo Tauchi, Shinichiro Okamoto, Koichi Miyamura, Kiyohiko Hatake, Hiromi Iwasaki, Itaru Matsumura, Noriko Usui, Tomoki Naoe, Meera Tugnait, Narayana I Narasimhan, Stephanie Lustgarten, Heinrich Farin, Frank Haluska, Kazuma Ohyashiki
In this ongoing Phase 1/2 study (NCT01667133), we evaluated ponatinib and assessed its recommended dose in Japanese patients with chronic myeloid leukemia (CML) resistant/intolerant to dasatinib or nilotinib, or with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) resistant/intolerant to ≥1 tyrosine kinase inhibitor (TKI). The primary endpoints were safety of the recommended dose (Phase 1) and major cytogenetic response (MCyR) by 12 months in chronic-phase CML (CP-CML) patients or major hematologic response (MaHR) by 6 months in patients with advanced phase disease (Phase 2)...
April 25, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28441234/validation-of-an-administrative-definition-of-icu-admission-using-revenue-center-codes
#15
Gary E Weissman, Rebecca A Hubbard, Rachel Kohn, George L Anesi, Scott Manaker, Meeta Prasad Kerlin, Scott D Halpern
OBJECTIVES: Describe the operating characteristics of a proposed set of revenue center codes to correctly identify ICU stays among hospitalized patients. DESIGN: Retrospective cohort study. We report the operating characteristics of all ICU-related revenue center codes for intensive and coronary care, excluding nursery, intermediate, and incremental care, to identify ICU stays. We use a classification and regression tree model to further refine identification of ICU stays using administrative data...
April 22, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28419558/age-but-not-philadelphia-positivity-impairs-outcome-in-older-elderly-patients-with-acute-lymphoblastic-leukemia-in-sweden
#16
Piotr Kozlowski, Emma Lennmyr, Lucia Ahlberg, Per Bernell, Erik Hulegårdh, Holger Karbach, Karin Karlsson, Beata Tomaszewska-Toporska, Maria Åström, Heléne Hallböök
OBJECTIVES: Older/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials. METHODS: Using Swedish national leukemia registries, we investigated disease/patient characteristics, treatment choices, outcome, and the impact of an age-adapted protocol (introduced in 2009) in this population-based study of patients aged 55-85 years, diagnosed with ALL 2005-2012. RESULTS: Of 174 patients, 82% had B-phenotype, 11% Burkitt leukemia (excluded), and 7% T-phenotype...
April 18, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28411309/calreticulin-mutations-in-bulgarian-mpn-patients
#17
Ivan Pavlov, Evgueniy Hadjiev, Tzvetan Alaikov, Sylva Spassova, Angel Stoimenov, Elissaveta Naumova, Velizar Shivarov, Milena Ivanova
Somatic mutations in JAK2, MPL and CALR are recurrently identified in most of the cases with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs). We applied four molecular genetic methods for identification of CALR exon 9 mutations, including high resolution melt (HRM) analysis, Sanger sequencing, semiconductor target genes sequencing and whole exome sequencing. A total of 78 patients with myeloid malignancies were included in the study. We identified 14 CALR exon 9 mutated cases out of 78 studied patients with myeloid malignancies...
April 14, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28408464/targetable-kinase-gene-fusions-in-high-risk-b-all-a-study-from-the-children-s-oncology-group
#18
Shalini C Reshmi, Richard C Harvey, Kathryn G Roberts, Eileen Stonerock, Amy Smith, Heather Jenkins, I-Ming Chen, Marc Valentine, Yu Liu, Yongjin Li, Ying Shao, John Easton, Debbie Payne-Turner, Zhaohui Gu, Thai Hoa Tran, Jonathan V Nguyen, Meenakshi Devidas, Yunfeng Dai, Nyla A Heerema, Andrew J Carroll, Elizabeth A Raetz, Michael J Borowitz, Brent L Wood, Anne L Angiolillo, Michael J Burke, Wanda L Salzer, Patrick A Zweidler-McKay, Karen R Rabin, William L Carroll, Jinghui Zhang, Mignon L Loh, Charles G Mullighan, Cheryl L Willman, Julie M Gastier-Foster, Stephen P Hunger
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype characterized by genomic alterations that activate cytokine receptor and kinase signaling. We examined the frequency and spectrum of targetable genetic lesions in a retrospective cohort of 1389 consecutively diagnosed childhood B-ALL patients with high-risk clinical features and/or elevated minimal residual disease at the end of remission induction therapy. The Ph-like gene expression profile was identified in 341 of 1389 patients, 57 of which were excluded from additional analysis because of the presence of BCR-ABL1 (n=46) or ETV6-RUNX1 (n=11)...
April 13, 2017: Blood
https://www.readbyqxmd.com/read/28406385/retrospective-chart-review-of-hospitalizations-and-costs-associated-with-the-treatment-of-adults-with-philadelphia-negative-b-cell-relapsed-or-refractory-acute-lymphoblastic-leukemia-in-belgium
#19
Johan Maertens, Carlos Graux, Dimitri Breems, Violaine Havelange, Sebastian Wittnebel, Daniëlle Strens, Caroline Hoefkens
OBJECTIVES: To quantify hospitalizations and costs among adults with Philadelphia-negative relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (ALL) who received current salvage chemotherapies in Belgium. METHODS: A retrospective chart review identified patients aged ≥18 years and hospitalized between 2005 and 2015 for Ph-negative R/R B-cell ALL. Data were collected from the index date (first diagnosis of R/R ALL) until death or loss to follow-up...
April 13, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28405136/ifosfamide-induced-encephalopathy-precipitated-by-aprepitant-a-rarely-manifested-side-effect-of-drug-interaction
#20
Pritam Sureshchandra Kataria, Pradip Piraji Kendre, Apurva A Patel
Central nervous system (CNS) toxicity has been reported in approximately 10%-30% of patients receiving intravenous infusions of ifosfamide. Encephalopathy is a rare but serious CNS adverse reaction in these patients, and although usually transient and reversible, may cause persistent neurological dysfunction or death. Clinical features range from fatigue and confusion to coma and death. Ifosfamide forms backbone of various treatment regimens including curative treatment and palliative chemotherapy regimen. Precipitation of ifosfamide-induced encephalopathy (IIE) by aprepitant has been reported in the literature rarely...
January 2017: Journal of Pharmacology & Pharmacotherapeutics
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