Letter
Hematology
Birgitte Klug Albertsen, Line Stensig Lynggaard, Kjeld Schmiegelow
Summary: This study evaluated the safety and efficacy of eryaspase in non-high-risk ALL patients. The results showed that eryaspase maintained effective asparaginase enzyme activity after the first infusion, with a half-life of approximately 15.3 days. Few patients experienced clinical allergy associated with enzyme inactivation, but replacement therapy was successfully completed. Therefore, eryaspase has good tolerability and effectiveness in continuing asparaginase treatment after hypersensitivity.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
Line Stensig Lynggaard, Goda Vaitkeviciene, Cecilia Langenskiold, Anne Kristine Lehmann, Paivi M. Lahteenmaki, Kristi Lepik, Iman El Hariry, Kjeld Schmiegelow, Birgitte Klug Albertsen
Summary: This study evaluated the safety and efficacy of eryaspase in treating patients with acute lymphoblastic leukaemia. The results showed that eryaspase was well tolerated and successfully completed the replacement therapy for most patients, allowing them to continue receiving asparaginase treatment.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Review
Pediatrics
Luke Maese, Rachel E. Rau
Summary: Cure rates for pediatric acute lymphoblastic leukemia (ALL) have significantly improved in the past five decades, largely due to the development and understanding of combination chemotherapy. Asparaginase, a recent addition to ALL chemotherapy, plays a crucial role in therapy by depleting the essential amino acid asparagine. Its unique toxicity profile, including hypersensitivity reactions, and the need for therapeutic drug monitoring have influenced the incorporation of asparaginase into ALL treatment. Despite its long-term use and standard-of-care status, there is still room for further improvement in the utilization of asparaginase therapy.
FRONTIERS IN PEDIATRICS
(2022)
Article
Oncology
Priyadarshani Dharia, Michael D. Swartz, M. Brooke Bernhardt, Han Chen, M. Monica Gramatges, Philip J. Lupo, Austin L. Brown, Michael E. Scheurer
Summary: This study retrospectively analyzed 548 patients with acute lymphoblastic leukemia and found that older age, overweight, and treatment intensity increased the risk of pegaspargase-associated toxicities.
LEUKEMIA & LYMPHOMA
(2022)
Article
Hematology
Wojciech Lizurej, Lukasz Mazurkiewicz, Michal Kowalski, Sylwia Szydlowska, Michal Wyrzykowski, Krzysztof Lewandowski
Summary: Mixed phenotype acute leukaemia (MPAL) is a challenging disease to treat with poor overall survival. A case of a 36-year-old woman diagnosed with MPAL was successfully treated with a protocol containing PEG-asparaginase, however, she developed a complication of brain sinus thrombosis. The patient achieved complete remission and underwent allo-HSCT with good outcomes.
THROMBOSIS JOURNAL
(2023)
Article
Oncology
Leiah J. Brigitha, Marta Fiocco, Rob Pieters, Birgitte K. Albertsen, Gabriele Escherich, Elixabet Lopez-Lopez, Veerle Mondelaers, Ajay Vora, Lynda Vrooman, Kjeld Schmiegelow, Inge M. van der Sluis
Summary: This study compares the incidence of allergic reactions caused by PEGasparaginase in different pediatric acute lymphoblastic leukemia (ALL) protocols. The results show that the incidence of allergic reactions is lower in protocols using PEGasparaginase as first-line treatment compared to those using native Escherichia coli asparaginase or PEGasparaginase after E.coli asparaginase. Postinduction phase, a higher number of PEGasparaginase-free intervals, and initiation of PEGasparaginase in postinduction phase are risk factors for allergic reactions.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Hematology
Hisashi Ishida, Toshihiko Imamura, Yasuhisa Tatebe, Takashi Ishihara, Kimiyoshi Sakaguchi, Souichi Suenobu, Atsushi Sato, Yoshiko Hashii, Takao Deguchi, Yoshihiro Takahashi, Daiichiro Hasegawa, Takako Miyamura, Akihiro Iguchi, Koji Kato, Akiko Saito-Moriya, Junichi Hara, Keizo Horibe
Summary: Asparaginase is a vital drug for ALL treatment, but discontinuation often leads to compromised patient outcomes. The ALL-02 protocol introduced additional chemotherapies and intense corticosteroid administration to compensate for asparaginase discontinuation. However, discontinuation of asparaginase was found to be an independent poor prognostic factor for EFS, and additional chemotherapies failed to fully compensate for its discontinuation. The study suggests that intensive corticosteroid treatment may help reduce allergy to asparaginase.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Review
Oncology
Leiah J. Brigitha, Rob Pieters, Inge M. van der Sluis
Summary: This review evaluates the optimal amount of asparaginase needed for childhood ALL treatment outcomes. While the level of exposure does not impact the outcome as long as therapeutic asparaginase activity levels are reached, the duration of exposure does have an effect on the outcome, with no clear cutoff for optimal exposure duration established. Other factors such as immunophenotype, (cyto)genetic subgroups, risk group stratification, and backbone therapy also influence the optimal exposure duration.
EUROPEAN JOURNAL OF CANCER
(2021)
Review
Hematology
Yannis K. Valtis, Andrew E. Place, Lewis B. Silverman, Lynda M. Vrooman, Daniel J. DeAngelo, Marlise R. Luskin
Summary: Osteonecrosis (ON) is a complication of acute lymphoblastic leukaemia (ALL) treatment, with patient and treatment-specific risk factors. Age is consistently identified as a key risk factor, with adolescents at higher risk. Limited studies on adults suggest that adolescents and young adults (AYAs) treated with specific regimens are more at risk. Effective strategies for prevention and management of osteonecrosis and other orthopaedic complications are lacking. Further research and evidence-based guidelines are needed, particularly for high-risk AYAs being treated with paediatric-inspired regimens.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
RuiQi Chen, Eshetu G. Atenafu, Jack Seki, Xing Liu, Steven Chan, Vikas Gupta, Dawn Maze, Andre C. Shuh, Mark D. Minden, Karen Yee, Aaron D. Schimmer, Hassan Sibai
Summary: This study found that PEG-ASP is associated with a higher incidence of VTE compared to L-ASP in patients with ALL, despite prophylactic anticoagulation. Further VTE mitigation strategies are needed for adult patients receiving PEG-ASP.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Cell Biology
Cheng-Yu Tsai, Toshie Saito, Mayur Sarangdhar, Maisam Abu-El-Haija, Li Wen, Bomi Lee, Mang Yu, Den A. Lipata, Murli Manohar, Monique T. Barakat, Kevin Contrepois, Thai Hoa Tran, Yves Theoret, Na Bo, Ying Ding, Kristen Stevenson, Elena J. Ladas, Lewis B. Silverman, Loredana Quadro, Tracy G. Anthony, Anil G. Jegga, Sohail Z. Husain
Summary: A systems approach revealed that vitamin A can reduce the risk of asparaginase-associated pancreatitis (AAP). Lower levels of vitamin A were found in ALL patients who developed pancreatitis. Therefore, vitamin A supplementation should be considered in preventing or treating AAP.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Genetics & Heredity
Arcangelo Iannuzzi, Mario Annunziata, Giuliana Fortunato, Carola Giacobbe, Daniela Palma, Alessandro Bresciani, Emilio Aliberti, Gabriella Iannuzzo
Summary: PEG-asparaginase is a standard treatment for acute lymphoblastic leukaemia, but high doses can cause severe side effects. This case report describes a 28-year-old male patient who developed severe hypertriglyceridemia following treatment with PEG-asparaginase. Genetic analysis revealed a rare variant and its association with common SNPs related to increased plasma triglyceride levels. This is the first reported case of a genetic variant associated with SNPs in the onset of severe drug-induced hypertriglyceridemia.
FRONTIERS IN GENETICS
(2022)
Article
Medicine, Research & Experimental
Tong Lin, Tajhia Whigham, Indrasiri Fernando, Mi Rim Choi, Qi Wang, Jeffrey A. Silverman
Summary: JZP458 is a recombinant Erwinia chrysanthemi asparaginase used for hypersensitive ALL/LBL patients. A PopPK model was established for intramuscular JZP458, finding a one-compartment model with mixed-order absorption and linear elimination. The model suggests that a dose of 25/25/50 mg/m(2) on MWF or 25 mg/m(2) every 48 hours is suitable for ALL/LBL patients.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Oncology
Sarah Menig, Andrew Dinh, Jonathan Angus, Sarah Tucker, Kasey J. Leger, Teresa Rushing, Etan Orgel
Summary: The implementation of universal premedication (UPM) prior to pegylated l-asparaginase (PEG) infusion did not reduce the incidence or severity of hypersensitivity reactions (HSRs). Alternative strategies are urgently needed to decrease the occurrence of HSRs.
PEDIATRIC BLOOD & CANCER
(2023)
Article
Oncology
Meghan Pike, Ketan Kulkarni, Tamara MacDonald
Summary: There is substantial variation in asparaginase activity monitoring practices across different medical centers in Canada, highlighting the need for a national practice guideline on asparaginase activity monitoring.
JOURNAL OF ONCOLOGY PHARMACY PRACTICE
(2023)