Allergic complications of L-asparaginase therapy in children with acute lymphoblastic leukaemia

Abstract

Introduction. L-asparaginase (L-ASP) is one of the most effective medications for the treatment of acute lymphoblastic leukaemia (ALL) in children, and allergic reactions to the therapy are considered the most significant side effects. Objective. The aim of this study was to determine the prevalence and type of allergic reactions, as well as to identify potential risk factors for the development of allergic reactions during L-ASP therapy in children with ALL. Methods. The study encompassed 70 patients under 18 years of age, who were treated at the Institute for Child and Youth Healthcare of Vojvodina, Novi Sad in the period January 2000 - June 2009. We analyzed the frequency and type of allergic reactions during the administration of L-ASP, the onset of allergic reaction in relation to the phase of therapy of underlying disease, as well as the prevalence of allergic reactions in relation to drug administration method. Results. Allergic reaction manifested in 17 patients (24%). In 14 patients (82%) allergic reaction to L-ASP manifested as urticaria, bronchospasm or anaphylaxis, whereas a mild local reaction was observed in only three patients (18%). In a group treated, according to the high-risk protocol, the prevalence of allergic reactions was statistically significantly higher in the intermediate-risk group of patients (p<0.01), i.e. statistically significantly more frequent, as compared to the standard-risk group of patients (p<0.05). The majority of patients (11; 65%) developed allergic reactions to the 9th dose of L-ASP, i.e. the first dose during the reinduction phase. The time interval between the last L-ASP dose in the induction phase and the 1st dose in the reinduction phase was at least four weeks. With respect to administration method, the majority of patients (16; 94%) developed allergic reaction after intravenous application of L-ASP. Conclusion. Potential risk factors for the development of allergic reaction to L-ASP are a high-risk therapy group, intravenous administration route and repeated application of the drug after at least four-week cessation period.Uvod. Jedan od najdelotvornijih lekova koji se primenjuju u lecenju dece obolele od akutne limfoblastne leukemije (ALL) jeste L-asparaginaza (L-ASP), a najznacajniji nezeljeni efekti tokom njegove primene jesu alergijske reakcije. Cilja rada. Cilj rada bio je da se odrede ucestalost i tip alergijskih reakcija, te ustanove faktori rizika koji mogu dovesti do razvoja alergije tokom primene L-ASP kod dece sa ALL. Metode rada. Istrazivanje je obuhvatilo 70 bolesnika uzrasta do 18 godina koji su leceni u Institutu za zdravstvenu zastitu dece i omladine Vojvodine u Novom Sadu od januara 2000. do juna 2009. godine. Analizirani su: ucestalost i tip alergijskih reakcija tokom primene L-ASP, vreme pojave alergijskih reakcija u odnosu na fazu lecenja osnovne bolesti i ucestalost alergijskih reakcija u zavisnosti od nacina primene leka. Rezultati. Alergijska reakcija se ispoljila kod 17 ispitanika (24%). Kod 14 bolesnika (82%) ona se manifestovala kao urtikarija, bronhospazam ili anafilaksa, a kod tri bolesnika (18%) kao blaga lokalna reakcija. U grupi dece lecene prema protokolu za visok rizik ucestalost alergijskih reakcija bila je statisticki visoko znacajno cesca nego u grupi bolesnika srednjeg rizika (p<0,01), odnosno statisticki znacajno cesca nego kod bolesnika sa standardnim rizikom (p<0,05). Alergijske reakcije su se kod 11 bolesnika (65%) javile po primeni devete doze L-ASP, odnosno prve doze tokom faze reindukcije, a interval izmedju poslednje L-ASP u indukciji i prve doze u reindukciji bio je najmanje cetiri nedelje. U pogledu nacina primene leka, kod najveceg broja ispitanika (16; 94%) alergijska reakcija se razvila nakon intravenske primene L-ASP. Zakljucak. Moguci faktori rizika za razvoj alergije na L-ASP su terapijska grupa visokog rizika, intravenska primena i ponovna primena leka nakon pauze od najmanje cetiri nedelje.