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asparaginase pancreatitis

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https://www.readbyqxmd.com/read/28736188/asparaginase-associated-pancreatitis-in-childhood-acute-lymphoblastic-leukaemia-an-observational-ponte-di-legno-toxicity-working-group-study
#1
Benjamin O Wolthers, Thomas L Frandsen, André Baruchel, Andishe Attarbaschi, Shlomit Barzilai, Antonella Colombini, Gabriele Escherich, Kathrine Grell, Hiroto Inaba, Gábor Kovacs, Der-Cherng Liang, Marion Mateos, Veerle Mondelaers, Anja Möricke, Tomasz Ociepa, Sujith Samarasinghe, Lewis B Silverman, Inge M van der Sluis, Martin Stanulla, Lynda M Vrooman, Michihiro Yano, Ester Zapotocka, Kjeld Schmiegelow
BACKGROUND: Survival for childhood acute lymphoblastic leukaemia surpasses 90% with contemporary therapy; however, patients remain burdened by the severe toxic effects of treatment, including asparaginase-associated pancreatitis. To investigate the risk of complications and risk of re-exposing patients with asparaginase-associated pancreatitis to asparaginase, 18 acute lymphoblastic leukaemia trial groups merged data for this observational study. METHODS: Patient files from 26 trials run by 18 trial groups were reviewed on children (aged 1·0-17·9 years) diagnosed with t(9;22)-negative acute lymphoblastic leukaemia between June 1, 1996, and Jan 1, 2016, who within 50 days of asparaginase exposure developed asparaginase-associated pancreatitis...
July 20, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28574850/whole-exome-sequencing-identified-genetic-risk-factors-for-asparaginase-related-complications-in-childhood-all-patients
#2
Rachid Abaji, Vincent Gagné, Chang Jiang Xu, Jean-François Spinella, Francesco Ceppi, Caroline Laverdière, Jean-Marie Leclerc, Stephen E Sallan, Donna Neuberg, Jeffery L Kutok, Lewis B Silverman, Daniel Sinnett, Maja Krajinovic
Allergy, pancreatitis and thrombosis are common side-effects of childhood acute lymphoblastic leukemia (ALL) treatment that are associated with the use of asparaginase (ASNase), a key component in most ALL treatment protocols. Starting with predicted functional germline variants obtained through whole-exome sequencing (WES) data of the Quebec childhood ALL cohort we performed exome-wide association studies with ASNase-related toxicities. A subset of top-ranking variants was further confirmed by genotyping (N=302) followed by validation in an independent replication group (N=282); except for thrombosis which was not available for that dataset...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28552244/ca-2-signalling-underlying-pancreatitis
#3
REVIEW
J V Gerasimenko, S Peng, T Tsugorka, O V Gerasimenko
In spite of significant scientific progress in recent years, acute pancreatitis (AP) is still a dangerous and in up to 5% of cases deadly disease with no specific cure. It is self-resolved in the majority of cases, but could result in chronic pancreatitis (CP) and increased risk of pancreatic cancer (PC). One of the early events in AP is premature activation of digestive pro-enzymes, including trypsinogen, inside pancreatic acinar cells (PACs) due to an excessive rise in the cytosolic Ca(2+) concentration, which is the result of Ca(2+) release from internal stores followed by Ca(2+) entry through the store operated Ca(2+) channels in the plasma membrane...
May 18, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28440015/hypertriglyceridemia-during-asparaginase-treatment-in-children-with-acute-lymphoblastic-leukemia-correlates-with-antithrombin-activity-in-adolescents
#4
Lisa Persson, Arja Harila-Saari, Ida Hed Myrberg, Mats Heyman, Anna Nilsson, Susanna Ranta
BACKGROUND: Asparaginase (ASP) is a cornerstone in the treatment of acute lymphoblastic leukemia (ALL). It is also known for its ability to cause side effects, such as allergy and pancreatitis, as well as lipid and coagulation disturbances. The most important laboratory abnormalities are hypertriglyceridemia (HTG) and low antithrombin (AT). HTG is usually considered to be transient and benign in children with ALL, whereas low AT activity predisposes to thrombosis. Studies on the incidence and significance of HTG in children with ALL are scarce, and their findings have not always been congruent...
April 25, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28413626/non-infectious-chemotherapy-associated-acute-toxicities-during-childhood-acute-lymphoblastic-leukemia-therapy
#5
REVIEW
Kjeld Schmiegelow, Klaus Müller, Signe Sloth Mogensen, Pernille Rudebeck Mogensen, Benjamin Ole Wolthers, Ulrik Kristoffer Stoltze, Ruta Tuckuviene, Thomas Frandsen
During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia...
2017: F1000Research
https://www.readbyqxmd.com/read/28375864/risk-factors-for-asparaginase-associated-pancreatitis-a-systematic-review
#6
Judy-April Oparaji, Fateema Rose, Debra Okafor, Amari Howard, Rose L Turner, Abrahim I Orabi, Craig Byersdorfer, Qi Mi, Kim Ritchey, Mark E Lowe, Sohail Z Husain
GOALS: To evaluate potential risk factors for the development of asparaginase-associated pancreatitis (AAP), we performed a systematic review of the current literature from January 1946 through May 2015. BACKGROUND: Asparaginase, a primary treatment for the most common childhood cancer, acute lymphoblastic leukemia (ALL), is a well-described cause of pancreatitis. Further, pancreatitis is among the most burdensome and common complications of asparaginase treatment and represents a major reason for early-drug termination and inferior outcomes...
April 3, 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/28355969/incidence-of-asparaginase-related-hepatotoxicity-pancreatitis-and-thrombotic-events-in-adults-with-acute-lymphoblastic-leukemia-treated-with-a-pediatric-inspired-regimen
#7
Trevor N Christ, Wendy Stock, Randall W Knoebel
Asparaginase is a critical component of acute lymphoblastic leukemia (ALL) treatment in children; however, its use in adults is often avoided as a result of toxicities including hepatotoxicity, thrombosis, and pancreatitis which have been reported more commonly in adults than in children. In this retrospective analysis, short-acting L-asparaginase (L-ASP) and long-acting polyethylene glycol (PEG)-asparaginase (PEG-ASP) were compared for grade 3-4 toxicities and characterized by patient and drug-related factors to identify strategies for toxicity avoidance in adults with ALL...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28349445/prophylactic-use-of-octreotide-for-asparaginase-induced-acute-pancreatitis
#8
Sachi Sakaguchi, Takeshi Higa, Mitsuyoshi Suzuki, Junya Fujimura, Toshiaki Shimizu
In the present study, we sought to evaluate the prophylactic use of octreotide for asparaginase-induced acute pancreatitis. We reviewed the medical records of seven patients in two institutions who received prophylactic octreotide for re-administration of asparaginase after asparaginase-induced acute pancreatitis. Three patients completed asparaginase treatment without developing pancreatitis, and four experienced recurrence of pancreatitis. A literature search using PubMed identified four additional patients in whom asparaginase was successfully re-administered with octreotide...
August 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28331334/safety-efficacy-and-clinical-utility-of-asparaginase-in-the-treatment-of-adult-patients-with-acute-lymphoblastic-leukemia
#9
REVIEW
Jamie Koprivnikar, James McCloskey, Stefan Faderl
Adults with acute lymphoblastic leukemia (ALL) are known to have inferior outcomes compared to the pediatric population. Although the reasons for this are likely manyfold, the agents utilized and the increased intensity of pediatric treatments compared to adult treatments are likely significant contributing factors. Asparaginase, an enzyme that converts asparagine to aspartic acid, forms the backbone of almost all pediatric regimens and works by depleting extracellular asparagine, which ALL cells are unable to synthesize...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28219133/-clinical-observation-on-lop-regimen-combined-with-imrt-treatment-for-early-nasal-nk-t-cell-lymphoma
#10
Y F Hu, Y H Huang, T Wu, Y Zhang, X M Liu, Y Song, J Y Gan
Objective: To observe the clinical efficacy and safety of the LOP regimen (L-asparaginase, vincristine, dexamethasone) combined with intensity modulated radiation therapy(IMRT)in the treatment of early nasal NK/T cell lymphoma. Method: Clinical data of 65 patients with nasal NK/T cell lymphoma treated with LOP chemotherapy combined with IMRT at the Guizhou Province Tumor Hospital between March 2010 and January 2015 were retrospectively analyzed. Results: Among the 65 patients, 39 cases obtained complete remission (CR), 18 cases obtained partial remission(PR), 1 case obtained stable disease (SD), 7 cases had progressive disease(PD)...
February 14, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27599414/minimal-contribution-of-severe-hypertriglyceridemia-in-l-asparaginase-associated-pancreatitis-developed-in-a-child-with-acute-lymphocytic-leukemia
#11
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
#12
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...
January 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27535145/incidence-and-clinical-associations-of-childhood-acute-pancreatitis
#13
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-phenotype-and-genotype-in-the-nopho-all2008-protocol
#14
B O Wolthers, T L Frandsen, J Abrahamsson, B K Albertsen, L R Helt, M Heyman, Ó G Jónsson, L T Kõrgvee, B Lund, R A Raja, K K Rasmussen, M Taskinen, M Tulstrup, G E Vaitkevičienė, R Yadav, R Gupta, K Schmiegelow
Asparaginase (ASP)-associated pancreatitis (AAP) occurs during acute lymphoblastic leukemia treatment. Among 1285 children (1.0-17.9 years) diagnosed during July 2008-December 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 the 20 re-exposed to ASP, 9 (45%) developed a second AAP...
February 2017: 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
#15
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
#16
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
#17
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
#18
COMPARATIVE STUDY
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
#19
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
#20
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
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