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asparaginase pancreatitis

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https://www.readbyqxmd.com/read/27599414/minimal-contribution-of-severe-hypertriglyceridemia-in-l-asparaginase-associated-pancreatitis-developed-in-a-child-with-acute-lymphocytic-leukemia
#1
Yoshinori Goto, Ryosei Nishimura, Atsushi Nohara, Shintaro Mase, Toshihiro Fujiki, Hitoshi Irabu, Rie Kuroda, Raita Araki, Yasuhiro Ikawa, Hideaki Maeba, Akihiro Yachie
A 10-year-old girl developed L-asparaginase (ASP)-associated pancreatitis during chemotherapy for acute lymphocytic leukemia. Her symptoms showed alleviation with continuous regional arterial infusion of protease inhibitor and systemic somatostatin analog therapy. She had intermittent and marked hypertriglyceridemia, an initial trigger for pancreatitis, probably as a side effect of ASP and steroids. However, we considered the pancreatitis to have developed mainly because of factors other than hypertriglyceridemia as lipoprotein analysis confirmed chylomicron levels to be nearly undetectable...
August 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27555294/asparaginase-associated-pancreatitis-is-not-predicted-by-hypertriglyceridemia-or-pancreatic-enzyme-levels-in-children-with-acute-lymphoblastic-leukemia
#2
Raheel Altaf Raja, Kjeld Schmiegelow, Ditte Nørbo Sørensen, Thomas Leth Frandsen
BACKGROUND: l-Asparaginase is an important drug for treatment of childhood acute lymphoblastic leukemia (ALL), but is associated with serious toxicities, including pancreatitis and hypertriglyceridemia (HTG). Asparaginase-associated pancreatitis (AAP) is a common reason for stopping asparaginase treatment. The aim of this study was to explore if HTG or early elevations in pancreatic enzymes were associated with the subsequent development of AAP. METHOD: Children (1...
August 24, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27535145/incidence-and-clinical-associations-of-childhood-acute-pancreatitis
#3
Abdalmonem A Majbar, Eleri Cusick, Paul Johnson, Richard M Lynn, Linda P Hunt, Julian P H Shield
OBJECTIVES: To establish the UK incidence and clinical associations of acute pancreatitis (AP) in children aged 0 to 14 years. METHODS: Monthly surveillance of new cases of AP in children under 15 years of age through the British Pediatric Surveillance Unit conducted from April 2013 to April 2014 (inclusive) followed by 1-year administrative follow-up for all valid cases. RESULTS: Ninety-four cases (48 boys) fulfilled the diagnostic criteria...
September 2016: Pediatrics
https://www.readbyqxmd.com/read/27451978/asparaginase-associated-pancreatitis-a-study-on-pheno-and-genotype-in-the-nopho-all2008-protocol
#4
B O Wolthers, T L Frandsen, J Abrahamsson, B K Albertsen, L R Helt, M Heyman, Óg Jónsson, L-T Kõrgvee, B Lund, R A Raja, K K Rasmussen, M Taskinen, M R Tulstrup, G E Vaitkevičienė, R Yadav, R Gupta, K Schmiegelow
Asparaginase-associated pancreatitis (AAP) occurs during acute lymphoblastic leukemia treatment. Among 1285 children (1.0-17.9 years) diagnosed 7/2008-12/2014 and treated according to the Nordic/Baltic ALL2008 protocol, 86 (cumulative incidence=6.8%) developed AAP. Seventy-three cases were severe (diagnostic AAP criteria persisting >72 h) and 13 mild. Cases were older than controls (median: 6.5 vs 4.5 years; P=0.001). Pseudocysts developed in 28%. Of 20 re-exposed to ASP, nine (45%) developed a second AAP...
July 25, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27377732/calcium-and-adenosine-triphosphate-control-of-cellular-pathology-asparaginase-induced-pancreatitis-elicited-via-protease-activated-receptor-2
#5
Shuang Peng, Julia V Gerasimenko, Tatiana Tsugorka, Oleksiy Gryshchenko, Sujith Samarasinghe, Ole H Petersen, Oleg V Gerasimenko
Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca(2+) signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca(2+) elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca(2+) signals can be evoked by products of alcohol and fatty acids as well as bile acids...
August 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/27299599/a-pilot-study-of-intensified-peg-asparaginase-in-high-risk-acute-lymphoblastic-leukemia-children-s-oncology-group-study-aall08p1
#6
Vilmarie Rodriguez, John Kairalla, Wanda L Salzer, Elizabeth A Raetz, Mignon Lc Loh, Andrew J Carroll, Nyla A Heerema, Brent L Wood, Michael J Borowitz, Michael J Burke, Barbara L Asselin, Meenakshi Devidas, Naomi J Winick, William L Carroll, Stephen P Hunger, ZoAnn E Dreyer
AALL08P1 was designed to determine whether biweekly intensified pegaspargase (I-PEG) was feasible and safe in pediatric patients with newly diagnosed high-risk B-precursor lymphoblastic leukemia when given with Children's Oncology Group hemiaugmented BFM therapy. High-risk average (HR-Avg) patients received standard pegaspargase dosing (6 doses), whereas high-risk high (HR-High) patients received I-PEG biweekly from the start of Consolidation until day 1 of Maintenance. Feasibility and safety were defined in advance as ≥65% of patients tolerating at least 8 doses of I-PEG and 90% requiring ≤49 weeks from day 1 of Consolidation to the initiation of Maintenance...
August 2016: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/27299279/consensus-definitions-of-14-severe-acute-toxic-effects-for-childhood-lymphoblastic-leukaemia-treatment-a-delphi-consensus
#7
REVIEW
Kjeld Schmiegelow, Andishe Attarbaschi, Shlomit Barzilai, Gabriele Escherich, Thomas Leth Frandsen, Christina Halsey, Rachael Hough, Sima Jeha, Motohiro Kato, Der-Cherng Liang, Torben Stamm Mikkelsen, Anja Möricke, Riitta Niinimäki, Caroline Piette, Maria Caterina Putti, Elizabeth Raetz, Lewis B Silverman, Roderick Skinner, Ruta Tuckuviene, Inge van der Sluis, Ester Zapotocka
Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group...
June 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27178680/final-results-of-a-single-institution-experience-with-a-pediatric-based-regimen-the-augmented-berlin-frankfurt-m%C3%A3-nster-in-adolescents-and-young-adults-with-acute-lymphoblastic-leukemia-and-comparison-to-the-hyper-cvad-regimen
#8
Michael E Rytting, Elias J Jabbour, Jeffrey L Jorgensen, Farhad Ravandi, Anna R Franklin, Tapan M Kadia, Naveen Pemmaraju, Naval G Daver, Alessandra Ferrajoli, Guillermo Garcia-Manero, Marina Y Konopleva, Gautam Borthakur, Rebecca Garris, Sa Wang, Sherry Pierce, Kurt Schroeder, Steven M Kornblau, Deborah A Thomas, Jorge E Cortes, Susan M O'Brien, Hagop M Kantarjian
Several studies reported improved outcomes of adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) treated with pediatric-based ALL regimens. This prompted the prospective investigation of a pediatric Augmented Berlin-Frankfurt-Münster (ABFM) regimen, and its comparison with hyper-fractionated cyclophosphamide, vincristine, Adriamycin, and dexamethasone (hyper-CVAD) in AYA patients. One hundred and six AYA patients (median age 22 years) with Philadelphia chromosome- (Ph) negative ALL received ABFM from October 2006 through March 2014...
August 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27114598/clinical-and-genetic-risk-factors-for-acute-pancreatitis-in-patients-with-acute-lymphoblastic-leukemia
#9
Chengcheng Liu, Wenjian Yang, Meenakshi Devidas, Cheng Cheng, Deqing Pei, Colton Smith, William L Carroll, Elizabeth A Raetz, W Paul Bowman, Eric C Larsen, Kelly W Maloney, Paul L Martin, Leonard A Mattano, Naomi J Winick, Elaine R Mardis, Robert S Fulton, Deepa Bhojwani, Scott C Howard, Sima Jeha, Ching-Hon Pui, Stephen P Hunger, William E Evans, Mignon L Loh, Mary V Relling
PURPOSE: Acute pancreatitis is one of the common causes of asparaginase intolerance. The mechanism is unknown, and genetic predisposition to asparaginase-induced pancreatitis has not been previously identified. METHODS: To determine clinical risk factors for asparaginase-induced pancreatitis, we studied a cohort of 5,185 children and young adults with acute lymphoblastic leukemia, including 117 (2.3%) who were diagnosed with at least one episode of acute pancreatitis during therapy...
June 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/26968207/general-control-nonderepressible-2-deletion-predisposes-to-asparaginase-associated-pancreatitis-in-mice
#10
Lindsey Phillipson-Weiner, Emily T Mirek, Yongping Wang, W Geoffrey McAuliffe, Ronald C Wek, Tracy G Anthony
Treatment with the antileukemic agent asparaginase can induce acute pancreatitis, but the pathophysiology remains obscure. In the liver of mice, eukaryotic initiation factor 2 (eIF2) kinase general control nonderepressible 2 (GCN2) is essential for mitigating metabolic stress caused by asparaginase. We determined the consequences of asparaginase treatment on the pancreata of wild-type (WT, GCN2-intact) and GCN2-deleted (ΔGcn2) mice. Mean pancreas weights in ΔGcn2 mice treated with asparaginase for 8 days were increased (P < 0...
June 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/26549586/intravenous-pegylated-asparaginase-versus-intramuscular-native-escherichia-coli-l-asparaginase-in-newly-diagnosed-childhood-acute-lymphoblastic-leukaemia-dfci-05-001-a-randomised-open-label-phase-3-trial
#11
RANDOMIZED CONTROLLED TRIAL
Andrew E Place, Kristen E Stevenson, Lynda M Vrooman, Marian H Harris, Sarah K Hunt, Jane E O'Brien, Jeffrey G Supko, Barbara L Asselin, Uma H Athale, Luis A Clavell, Peter D Cole, Kara M Kelly, Caroline Laverdiere, Jean-Marie Leclerc, Bruno Michon, Marshall A Schorin, Jennifer J G Welch, Steven E Lipshultz, Jeffery L Kutok, Traci M Blonquist, Donna S Neuberg, Stephen E Sallan, Lewis B Silverman
BACKGROUND: l-asparaginase is a universal component of treatment for childhood acute lymphoblastic leukaemia, and is usually administered intramuscularly. Pegylated Escherichia coli asparaginase (PEG-asparaginase) has a longer half-life and is potentially less immunogenic than the native Escherichia coli (E coli) preparation, and can be more feasibly administered intravenously. The aim of the Dana-Farber Cancer Institute Acute Lymphoblastic Leukaemia Consortium Protocol 05-001 (DFCI 05-001) was to compare the relative toxicity and efficacy of intravenous PEG-asparaginase and intramuscular native E colil-asparaginase in children with newly diagnosed acute lymphoblastic leukaemia...
December 2015: Lancet Oncology
https://www.readbyqxmd.com/read/26475748/-hypertriglyceridemia-discorvered-on-a-pseudohyponatremia-induced-by-l-asparaginase-in-the-treatment-of-b-acute-lymphoblastic-leukemia-in-child
#12
Aurélie Morand, Vincent Barlogis, Frank Rouby, Rachel Reynaud, Céline Marrec, Gérard Michel
We report the case of a 6-year-old girl, admitted at the 32th days of chemotherapy induction of a B acute lymphoblastic leukemia for pseudohyponatremia (121 mmol/L), which revealed a major hypertriglyceridemia (125 g/L). The milky aspect of blood samples was remarquable. We suspected a hypertriglyceridemia induced by L-asparaginase. We introduced a treatment by hyperhydratation, insulinotherapy, free fat diet and one plasmapheresis. Decrease of hypertriglyceridemia was quickly observed. However on the tenth day she presented a pancreatitis...
October 16, 2015: Thérapie
https://www.readbyqxmd.com/read/26457414/asparaginase-associated-toxicity-in-children-with-acute-lymphoblastic-leukemia
#13
Nobuko Hijiya, Inge M van der Sluis
Asparaginase is an integral component of multiagent chemotherapy regimens for the treatment of children with acute lymphoblastic leukemia. Positive outcomes are seen in patients who are able to complete their entire prescribed course of asparaginase therapy. Toxicities associated with asparaginase use include hypersensitivity (clinical and subclinical), pancreatitis, thrombosis, encephalopathy, and liver dysfunction. Depending on the nature and severity of the toxicity, asparaginase therapy may be altered or discontinued in some patients...
2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/26421220/best-practices-in-adolescent-and-young-adult-patients-with-acute-lymphoblastic-leukemia-a-focus-on-asparaginase
#14
REVIEW
Nicolas Boissel, Leonard S Sender
The inclusion of asparaginase in chemotherapy regimens to treat acute lymphoblastic leukemia (ALL) has had a positive impact on survival in pediatric patients. Historically, asparaginase has been excluded from most treatment protocols for adolescent and young adult (AYA) patients because of perceived toxicity in this population, and this is believed to have contributed to poorer outcomes in these patients. However, retrospective analyses over the past 12 years have shown that 2-, 5-, and 7-year overall survival of AYA patients is significantly improved with pediatric versus adult protocols...
September 2015: Journal of Adolescent and Young Adult Oncology
https://www.readbyqxmd.com/read/26376459/activity-and-toxicity-of-intravenous-erwinia-asparaginase-following-allergy-to-e-coli-derived-asparaginase-in-children-and-adolescents-with-acute-lymphoblastic-leukemia
#15
MULTICENTER STUDY
Lynda M Vrooman, Ivan I Kirov, ZoAnn E Dreyer, Michael Kelly, Nobuko Hijiya, Patrick Brown, Richard A Drachtman, Yoav H Messinger, A Kim Ritchey, Gregory A Hale, Kelly Maloney, Yuan Lu, Paul V Plourde, Lewis B Silverman
BACKGROUND: Erwinia asparaginase is antigenically distinct from E.coli-derived asparaginase and may be used after E.coli-derived asparaginase hypersensitivity. In a single-arm, multicenter study, we evaluated nadir serum asparaginase activity (NSAA) and toxicity with intravenously administered asparaginase Erwinia chrysanthemi (IV-Erwinia) in children and adolescents with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma with hypersensitivity to E.coli-derived asparaginase...
February 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/26355551/asparagine-synthetase-expression-and-phase-i-study-with-l-asparaginase-encapsulated-in-red-blood-cells-in-patients-with-pancreatic-adenocarcinoma
#16
MULTICENTER STUDY
Jean-Baptiste Bachet, Fabien Gay, Raphaël Maréchal, Marie-Pierre Galais, Antoine Adenis, David Salako MsC, Jerome Cros, Pieter Demetter, Magali Svrcek, Armelle Bardier-Dupas, Jean-François Emile, Pascal Hammel, Christelle Ebenezer, Willy Berlier, Yann Godfrin, Thierry André
OBJECTIVES: Asparaginase encapsulated in erythrocytes (ERY-ASP) is a potentially effective drug in patients with pancreatic adenocarcinoma (PAC) with null/low asparagine synthetase (ASNS) expression. Our aims were to assess ASNS expression in PAC from a large cohort and its prognostic and/or predictive value and to conduct a phase I trial with ERY-ASP in patients with metastatic PAC. METHODS: Asparagine synthetase expression was evaluated using immunohistochemistry in resected PAC (471 patients) and in pairs of primary tumor and metastases (55 patients)...
October 2015: Pancreas
https://www.readbyqxmd.com/read/26331232/peg-asparaginase-induced-severe-hypertriglyceridemia
#17
Rodolfo J Galindo, Justin Yoon, Craig Devoe, Alyson K Myers
Asparaginase (ASP) is an effective chemotherapy agent extensively used in children with acute lymphocytic leukemia (ALL). There has been a recent interest in using ASP in adults with ALL, particularly the less toxic pegylated (PEG) formulation. Hypertriglyceridemia (HTG) is a rare complication of PEG-ASP therapy. We report two cases of obese patients who developed severe HTG after receiving PEG for ALL. Both patients were incidentally found to have severe HTG (TG of 4,330 and 4,420 mg/dL). In both patients, there was no personal or family history of dyslipidemia or hypothyroidism...
April 2016: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/26270775/serial-ultrasound-monitoring-for-early-recognition-of-asparaginase-associated-pancreatitis-in-children-with-acute-lymphoblastic-leukemia
#18
Raheel Altaf Raja, Kjeld Schmiegelow, Birthe Merethe Henriksen, Thomas Leth Frandsen
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children and L-asparaginase is an essential component of the treatment. Cessation of L-asparaginase decreases event free survival. Acute pancreatitis is the toxicity that most commonly results in cessation of L-asparaginase. We tested whether serial ultrasound examinations could predict asparaginase-associated pancreatitis (AAP). METHODS: Children (aged 1.0-17.9 years) with childhood ALL treated at the University Hospital Rigshopitalet, Copenhagen, according to the standard or intermediate risk arms of the NOPHO ALL2008 protocol, with PEG-asparaginase of 2 or 6 week intervals, for 30 weeks had their pancreas monitored using serial ultrasound in order to detect early signs of inflammation...
2015: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/26228669/clinical-characteristics-of-japanese-patients-with-severe-hypertriglyceridemia
#19
Hayato Tada, Masa-Aki Kawashiri, Takuya Nakahashi, Kunimasa Yagi, Daisuke Chujo, Azusa Ohbatake, Yukiko Mori, Shunsuke Mori, Mitsuhiro Kometani, Hiroshi Fujii, Atsushi Nohara, Akihiro Inazu, Hiroshi Mabuchi, Masakazu Yamagishi, Kenshi Hayashi
BACKGROUND: Although of interest, few data exist on the clinical characteristics of Japanese patients with an extremely high triglyceride level (≥ 1000 mg/dL). OBJECTIVE: We assessed the clinical characteristics of Japanese patients with an extremely high triglyceride level. METHODS: We investigated the presence of coronary artery disease, history of pancreatitis, the presence of fatty liver, and the potential causes of elevated triglyceride in Japanese subjects with an extremely high level of fasting triglyceride (≥ 1000 mg/dL) among 70,368 subjects whose serum triglyceride was measured for any reason at Kanazawa University Hospital from April 2004 to March 2014...
July 2015: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/26178806/asparaginase-treatment-side-effects-may-be-due-to-genes-with-homopolymeric-asn-codons-review-hypothesis
#20
REVIEW
Julian Banerji
The present treatment of childhood T-cell leukemias involves the systemic administration of prokaryotic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved...
September 2015: International Journal of Molecular Medicine
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