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Asparaginase

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https://www.readbyqxmd.com/read/28718698/pegging-down-risk-factors-for-peg-asparaginase-hepatotoxicity-in-patients-with-acute-lymphoblastic-leukemia-%C3%A2
#1
Caitlin R Rausch, Bernard L Marini, Lydia L Benitez, Allison Elias, Patrick W Burke, Dale Bixby, Anthony J Perissinotti
Asparaginase is commonly de-emphasized/omitted in adult acute lymphoblastic leukemia regimens due to poor tolerability, including hepatotoxicity (HTX). Adult patients (n = 100) given induction therapy containing pegylated asparaginase (PEG) from January 2008 to February 2016 were evaluated for HTX. Sixteen patients met criteria for HTX (direct bilirubin >3 g/dL). A multivariable model identified body surface area >2m(2) (OR 7.40; 95% CI: 1.73-31.61, p = .007), albumin <3 mg/dL (OR 4.62; 95% CI: 1...
July 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28698205/an-fc-engineered-cd19-antibody-eradicates-mrd-in-patient-derived-mll-rearranged-acute-lymphoblastic-leukemia-xenografts
#2
Denis M Schewe, Ameera Alsadeq, Cornelia Sattler, Lennart Lenk, Fotini Vogiatzi, Gunnar Cario, Simon Vieth, Thomas Valerius, Sophia Rosskopf, Fabian Meyersieck, Julia Alten, Martin Schrappe, Martin Gramatzki, Matthias Peipp, Christian Kellner
Antibody therapy constitutes a major advance in the treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). To evaluate the efficacy and the mechanisms of action of CD19 monoclonal antibody therapy in pediatric BCP-ALL, an Fc engineered CD19 antibody carrying the S239D/I332E mutation for improved effector cell recruitment (CD19-DE) was tested. Patient derived xenografts (PDX) of pediatric MLL-rearranged ALL were established in NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ (NSG) mice. Antibody CD19-DE was efficient in prolonging the survival of NSG mice in a minimal residual disease (MRD) model...
July 11, 2017: Blood
https://www.readbyqxmd.com/read/28697948/catalyzing-improvements-in-all-therapy-with-asparaginase
#3
REVIEW
Bernard L Marini, Anthony J Perissinotti, Dale L Bixby, Julia Brown, Patrick W Burke
Asparaginase remains a cornerstone of ALL therapy and is one of the key contributing factors to improved outcomes in adolescent and young adult (AYA) patients treated on pediatric protocols. Asparagine depletion has been associated with improved outcomes in ALL patients; this has led to an increased emphasis on optimizing asparagine depletion in ALL patients of all ages. To ensure adequate asparagine depletion, the use of therapeutic drug monitoring of asparaginase therapy holds much promise, yet remains underutilized in practice...
July 5, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28690619/characterization-of-three-l-asparaginases-from-maritime-pine-pinus-pinaster-ait
#4
Sonia H Van Kerckhoven, Fernando N de la Torre, Rafael A Cañas, Concepción Avila, Francisco R Cantón, Francisco M Cánovas
Asparaginases (ASPG, EC 3.5.1.1) catalyze the hydrolysis of the amide group of L-asparagine producing L-aspartate and ammonium. Three ASPG, PpASPG1, PpASPG2, and PpASPG3, have been identified in the transcriptome of maritime pine (Pinus pinaster Ait.) that were transiently expressed in Nicotiana benthamiana by agroinfection. The three recombinant proteins were processed in planta to active enzymes and it was found that all mature forms exhibited double activity asparaginase/isoaspartyl dipeptidase but only PpASPG1 was able to catalyze efficiently L-asparagine hydrolysis...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28675023/comparison-of-native-escherichia-coli-l-asparaginase-versus-pegylated-asparaginase-in-combination-with-ifosfamide-methotrexate-etoposide-and-prednisolone-imep-in-extranodal-nk-t-cell-lymphoma-nasal-type-ntcl
#5
Hyun Jee Kim, Chan-Young Ock, Tae Min Kim, Sung Hee Lee, Ju-Yeun Lee, Sun Hoi Jung, Yoon Sook Cho, Miso Kim, Bhumsuk Keam, Dong-Wan Kim, Il Han Kim, Dae Seog Heo
Purpose: The aim of this study was to compare asparaginase-related toxicities in two asparaginase preparations, namely native Escherichia coli (E. coli) L-asparaginase (L-ASP) and pegylated asparaginase (PEG-ASP) in combination with ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) in NK/T-cell lymphoma (NTCL). Materials and Methods: A total of 41 NTCL patients who received IMEP plus native E. coli L-ASP or PEG-ASP at Seoul National University Hospital were included in this study between January 2013 and March 2016...
July 3, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28671857/neurocognitive-functioning-of-children-treated-for-high-risk-b-acute-lymphoblastic-leukemia-randomly-assigned-to-different-methotrexate-and-corticosteroid-treatment-strategies-a-report-from-the-children-s-oncology-group
#6
Kristina K Hardy, Leanne Embry, John A Kairalla, Shanjun Helian, Meenakshi Devidas, Daniel Armstrong, Stephen Hunger, William L Carroll, Eric Larsen, Elizabeth A Raetz, Mignon L Loh, Wenjian Yang, Mary V Relling, Robert B Noll, Naomi Winick
Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for neurocognitive deficits that are associated with treatment, individual, and environmental factors. This study examined the impact of different methotrexate (MTX) and corticosteroid treatment strategies on neurocognitive functioning in children with high-risk B-lineage ALL. Methods Participants were randomly assigned to receive high-dose MTX with leucovorin rescue or escalating dose MTX with PEG asparaginase without leucovorin rescue...
July 3, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28671681/extracellular-vesicles-are-independent-metabolic-units-with-asparaginase-activity
#7
Nunzio Iraci, Edoardo Gaude, Tommaso Leonardi, Ana S H Costa, Chiara Cossetti, Luca Peruzzotti-Jametti, Joshua D Bernstock, Harpreet K Saini, Maurizio Gelati, Angelo Luigi Vescovi, Carlos Bastos, Nuno Faria, Luigi G Occhipinti, Anton J Enright, Christian Frezza, Stefano Pluchino
Extracellular vesicles (EVs) are membrane particles involved in the exchange of a broad range of bioactive molecules between cells and the microenvironment. Although it has been shown that cells can traffic metabolic enzymes via EVs, much remains to be elucidated with regard to their intrinsic metabolic activity. Accordingly, herein we assessed the ability of neural stem/progenitor cell (NSC)-derived EVs to consume and produce metabolites. Our metabolomics and functional analyses both revealed that EVs harbor L-asparaginase activity, catalyzed by the enzyme asparaginase-like protein 1 (Asrgl1)...
July 3, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28660740/prolonged-first-line-peg-asparaginase-treatment-in-pediatric-acute-lymphoblastic-leukemia-in-the-nopho-all2008-protocol-pharmacokinetics-and-antibody-formation
#8
Louise Tram Henriksen, Sofie Gottschalk Højfeldt, Kjeld Schmiegelow, Thomas Leth Frandsen, Peder Skov Wehner, Henrik Schrøder, Birgitte Klug Albertsen
BACKGROUND: As pegylated asparaginase is becoming the preferred first-line asparaginase preparation in the chemotherapy regimens of childhood acute lymphoblastic leukemia (ALL), there is a need to evaluate this treatment. METHODS: The aim of this study was to evaluate the pharmacokinetics of prolonged upfront biweekly PEG-asparaginase (where PEG is polyethylene glycol) treatment by measuring serum l-asparaginase activity and formation of anti-PEG-asparaginase antibodies...
June 29, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28660695/cerebral-sinus-venous-thrombosis-during-childhood-acute-lymphoblastic-leukemia-therapy-risk-factors-and-management
#9
Khaled M Ghanem, Raghida M Dhayni, Carol Al-Aridi, Nidale Tarek, Hani Tamim, Anthony K C Chan, Raya Saab, Miguel R Abboud, Hassan El-Solh, Samar A Muwakkit
BACKGROUND: Cerebral sinus venous thrombosis (CSVT) is a rare but serious complication of childhood acute lymphoblastic leukemia (ALL) therapy. No available consensus exists regarding its risk factors and appropriate management due to the rarity of cases. PROCEDURES: Out of 209 ALL patients aged 1-21 years treated at the Children's Cancer Center of Lebanon between May 2002 and May 2015, 13 developed CSVT during therapy. Patient characteristics, clinical management, and outcomes were studied...
June 29, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28652944/extranodal-natural-killer-t-cell-lymphoma-an-incidental-finding
#10
Ashley Althoff, Michael Bibliowicz
Extranodal natural killer/T-cell lymphoma (ENKTCL) is a rare form of non-Hodgkin lymphoma. This neoplasm is more prevalent in regions of Asia and Latin America and most commonly involves the sinonasal tract, presenting with signs of nasal obstruction, epistaxis, or sinus infection. It is a locally destructive and angioinvasive neoplasm. The treatment of ENKTCL is dependent on the extent of the tumor. For localized disease, the treatment is chemoradiation. For disseminated disease, treatment is mainly chemotherapy-based...
May 19, 2017: Curēus
https://www.readbyqxmd.com/read/28650467/genome-wide-loss-of-function-genetic-screening-identifies-opioid-receptor-%C3%AE-1-as-a-key-regulator-of-l-asparaginase-resistance-in-pediatric-acute-lymphoblastic-leukemia
#11
S M Kang, J L Rosales, V Meier-Stephenson, S Kim, K Y Lee, A Narendran
L-asparaginase is a critical chemotherapeutic agent for acute lymphoblastic leukemia (ALL). It hydrolyzes plasma asparagine into aspartate and NH3, causing asparagine deficit and inhibition of protein synthesis and eventually, leukemic cell death. However, patient relapse often occurs due to development of resistance. The molecular mechanism by which ALL cells acquire resistance to L-asparaginase is unknown. Therefore, we sought to identify genes that are involved in L-asparaginase resistance in primary leukemic cells...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28642445/identification-of-a-cytogenetic-and-molecular-subgroup-of-acute-myeloid-leukemias-showing-sensitivity-to-l-asparaginase
#12
Salvatore Nicola Bertuccio, Salvatore Serravalle, Annalisa Astolfi, Annalisa Lonetti, Valentina Indio, Anna Leszl, Andrea Pession, Fraia Melchionda
L-Asparaginase (L-Asp) is an enzyme that catalyzes the hydrolysis of L-asparagine to L-aspartic acid, and its depletion induces leukemic cell death. L-Asp is an important component of treatment regimens for Acute Lymphoblastic Leukemia (ALL). Sensitivity to L-Asp is due to the absence of L-Asparagine synthetase (ASNS), the enzyme that catalyzes the biosynthesis of L-asparagine. ASNS gene is located on 7q21.3, and its increased expression in ALLs correlates with L-Asp resistance. Chromosome 7 monosomy (-7) is a recurrent aberration in myeloid disorders, particularly in adverse-risk Acute Myeloid Leukemias (AMLs) and therapy-related myeloid neoplasms (t-MN), that leads to a significant downregulation of the deleted genes, including ASNS...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28628558/genetics-of-pleiotropic-effects-of-dexamethasone
#13
Laura B Ramsey, Stan Pounds, Cheng Cheng, Xueyuan Cao, Wenjian Yang, Colton Smith, Seth E Karol, Chengcheng Liu, John C Panetta, Hiroto Inaba, Jeffrey E Rubnitz, Monika L Metzger, Raul C Ribeiro, John T Sandlund, Sima Jeha, Ching-Hon Pui, William E Evans, Mary V Relling
OBJECTIVES: Glucocorticoids such as dexamethasone have pleiotropic effects, including desired antileukemic, anti-inflammatory, or immunosuppressive effects, and undesired metabolic or toxic effects. The most serious adverse effects of dexamethasone among patients with acute lymphoblastic leukemia are osteonecrosis and thrombosis. To identify inherited genomic variation involved in these severe adverse effects, we carried out genome-wide association studies (GWAS) by analyzing 14 pleiotropic glucocorticoid phenotypes in 391 patients with acute lymphoblastic leukemia...
June 16, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28622171/reactions-to-cytostatic-agents-in-children
#14
Josefina R Cernadas
PURPOSE OF REVIEW: The current review will focus on drug hypersensitivity reactions to chemotherapy specifically to those drugs most used in children. We know that potentially all chemotherapeutic agents can cause infusion reactions, generally defined as adverse drug reactions. Of these, some are Type A, defined as expected and described in the characteristics of the drug and others, and Type B, defined as unexpected reactions which cannot be explained by the known toxicity profile of the drug...
August 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28621166/l-asparaginase-for-newly-diagnosed-extra-nodal-nk-t-cell-lymphoma-systematic-review-and-meta-analysis
#15
Vadim S Pokrovsky, Denis Vinnikov
OBJECTIVES: The aim of this review was to compare the efficacy of asparaginase (ASP)-containing vs ASP-absent regimens in the first-line treatment of ENKTL patients. METHODS: The PRISMA protocol was used to search PubMed and Embase for both controlled and uncontrolled studies of ASP or alternative chemotherapy (CT) for newly diagnosed ENKTL, published in English by March 2017. The regimens were compared to calculate relative risk (RR) with 95% confidence interval (CI) of the overall response rate (ORR), complete response (CR) or partial response (PR)...
June 21, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28602129/from-the-children-s-oncology-group-evidence-based-recommendations-for-peg-asparaginase-nurse-monitoring-hypersensitivity-reaction-management-and-patient-family-education
#16
Deborah Woods, Kari Winchester, Alison Towerman, Katie Gettinger, Christina Carey, Karen Timmermann, Rachel Langley, Emily Browne
PEG-aspariginase is a backbone chemotherapy agent in pediatric acute lymphoblastic leukemia and in some non-Hodgkin lymphoma therapies. Nurses lack standardized guidelines for monitoring patients receiving PEG-asparaginase and for educating patients/families about hypersensitivity reaction risks. An electronic search of 6 databases using publication years 2000-2015 and multiple professional organizations and clinical resources was conducted. Evidence sources were reviewed for topic applicability. Each of the final 23 sources was appraised by 2 team members...
June 1, 2017: Journal of Pediatric Oncology Nursing: Official Journal of the Association of Pediatric Oncology Nurses
https://www.readbyqxmd.com/read/28596278/hla-drb1-07-01-hla-dqa1-02-01-hla-dqb1-02-02-haplotype-is-associated-with-a-high-risk-of-asparaginase-hypersensitivity-in-acute-lymphoblastic-leukemia
#17
Nóra Kutszegi, Xiaoqin Yang, András Gézsi, Géza Schermann, Dániel J Erdélyi, Ágnes F Semsei, Krisztina M Gábor, Judit C Sági, Gábor T Kovács, András Falus, Hongyun Zhang, Csaba Szalai
Hypersensitivity reactions are the most frequent dose-limiting adverse reactions to Escherichia coli-derived asparaginase in pediatric acute lymphoblastic leukemia patients. The aim of the present study was to identify associations between sequence-based Human Leukocyte Antigen Class II region alleles and asparaginase hypersensitivity in a Hungarian acute lymphoblastic leukemia population. Four-digit typing of HLA-DRB1 and HLA-DQB1 loci was performed in 359 pediatric acute lymphoblastic leukemia patients by using next-generation sequencing method...
June 8, 2017: Haematologica
https://www.readbyqxmd.com/read/28596071/genetic-and-metabolic-engineering-approaches-for-the-production-and-delivery-of-l-asparaginases-an-overview
#18
REVIEW
Jalaja Vidya, Syed Sajitha, Mrudula Vasudevan Ushasree, Raveendran Sindhu, Parameswaran Binod, Aravind Madhavan, Ashok Pandey
L-asparaginase is one of the protein drugs for countering leukemia and lymphoma. A major challenge in the therapeutic potential of the enzyme is its immunogenicity, low-plasma half-life and glutaminase activity that are found to be the reasons for toxicities attributed to asparaginase therapy. For addressing these challenges, several research and developmental activities are going on throughout the world for an effective drug delivery for treatment of cancer. Hence there is an urgent need for the development of asparaginase with improved properties for efficient drug delivery...
May 12, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28588188/a-young-boy-with-l-asparaginase-induced-seizure
#19
M A Aziz, N K Singh, M H Rahman, M R Khan, A L Kabir, M Begum
L-Asparaginase is a critical component in the treatment of acute lymphoblastic leukemia in children. It is known to cause coagulation abnormalities, thrombosis and hemorrhage in the central nervous system in addition to vasculitis and hypersensitivity reactions. This syndrome generally occurs after a few weeks of therapy and may occur after L-asparaginase therapy is completed. Seizures are uncommon symptoms. We report a case of seizure associated with L-asparaginase therapy but no evidence of hemorrhagic or thrombotic cerebrovascular events, completed in the department of Hematology of Bangabandhu Sheikh Mujib Medical University during March & April 2016...
April 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/28574850/whole-exome-sequencing-identified-genetic-risk-factors-for-asparaginase-related-complications-in-childhood-all-patients
#20
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
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