| Abstract | Uvod: Asparaginaza je osnovna komponenta kemoterapijskih protokola za liječenje pedijatrijske akutne limfoblastične leukemije (ALL) i ključan citostatik za postizanje 5-godišnje stope preživljenja oko 90% u razvijenim zemljama. Primjena asparaginaze udružena je sa značajnom toksičnosti. Cilj rada je ispitati učestalost, vrstu i intenzitet toksičnih učinaka asparaginaze te njihov utjecaj na konačni ishod liječenja.
Materijali i metode: U istraživanje je uključeno 33 djece (21 dječak i 12 djevojčica) s novodijagnosticiranom ALL, prosječne dobi 5,95±3,45 godina, koja su liječena na Zavodu za hematologiju, onkologiju i kliničku genetiku Klinike za pedijatriju Kliničkog bolničkog centra Rijeka od 1. siječnja 2013. do 31. prosinca 2022. godine. U svih bolesnika provedena je kemoterapija prema ALL IC-BFM 2009 protokolu.
Rezultati: Primjena asparaginaze je udružena sa čestom i značajnom toksičnosti. Najučestaliji toksični učinci asparaginaze su poremećaji koagulacije (hipofibrinogenemija i deficit antitrombina III), hiperglikemija, hipoalbuminemija, hiperbilirubinemija i transaminitis. Reakcije preosjetljivosti prisutne su u gotovo trećine pacijenata s ALL. Nema razlike u ukupnoj toksičnosti između različitih formulacija asparaginaze. Toksičnost nije bila udružena s nepotpunom terapijom.
Zaključak: Toksičnost asparaginaze je značajna, ali ne utječe na konačan ishod liječenja djece s ALL ako nije udružena s nepotpunom primjenom lijeka. U svakoj odluci o prekidu terapije asparaginazom treba uvijek procijeniti individualni rizik toksičnosti zbog nastavka terapije od rizika recidiva. |
| Abstract (english) | Introduction: Asparaginase is a basic component of chemotherapy protocols for the treatment of pediatric acute lymphoblastic leukemia (ALL), and a crucial cytotoxic drug to achieve a 5-year survival rate of 90% in developed countries. The administration of asparaginase is associated with significant toxicity. The aim of the study is to examine the frequency, type, and intensity of the toxic effects of asparaginase, and their impact on the outcome.
Materials and methods: The study included 33 children (21 boys and 12 girls) with the newly diagnosed ALL, with median age 5,95±3,45 years, who were treated at the Division of Hematology, Oncology and Clinical genetics, Department of Pediatrics, Clinical Hospital Centre Rijeka, from January 1st, 2013, to December 31st, 2022. All patients were treated according to ALL IC-BFM 2009 protocol.
Results: The administration of asparaginase is associated with frequent and significant toxicity. The commonest toxic effects include coagulation disorders (hypofibrinogenemia and antithrombin III deficiency), hyperglycemia, hypoalbuminemia, hyperbilirubinemia, and transaminitis. Hypersensitivity reactions were present in almost one third of patients. No difference in the overall toxicity was found between different formulations of asparaginase. Asparaginase-related toxicity was not associated with incomplete administration of the drug.
Conclusion: Asparaginase has a significant toxicity, but does not influence the treatment outcome in children with ALL if not associated with insufficient exposure to the drug. In any decision to discontinue asparaginase therapy, the individual risk of toxicity due to the continuation of therapy should always be assessed against the risk of relapse. |
