Influence of Different Asparaginase Formulations in the Prognosis of Children With Acute Lymphocytic Leukemia in Brazil: A Multicenter, Retrospective Controlled Study

Abstract

Background: Our research group recently showed that the only ASNase formulation available in Brazil from 2017 to 2018 when used at the same dose and frequency as the formulation provided previously did not reach, in most cases, the serum activity considered therapeutic. Based on these data, our goal was to assess the impact of these facts on the prognosis of children with ALL at 10 different pediatric oncology centers in our country. Methods: a multicenter retrospective observational study followed by prospective follow-up. Patients aged >1 and <18 years in first-line treatment followed up at 10 referral centers of Brazil, between 2014 and 2018 who received the formulation Leuginase® were identified (Group B). For each patient, the center registered 2 patients who received ASNase in the presentation of Aginasa® exclusively (Group A). Data collection was performed by searching for medical records and registered using Redcap® software. Findings: A total of 419 patients were included; 282 in Group A and 137 in Group B. Clinical features at diagnosis were similar in both groups. Group A had a 3-year OS and EFS of 91·8% and 84·8% respectively, while Group B had a 3-year OS of 83·8% (p= 0·003) and EFS of 76·1% (p = 0·008). Interpretation: There was an impact on 3-year OS and EFS of children who received an asparaginase formulation that previously showed inferior activity in laboratory analysis. This result highlights the importance of evaluating asparaginase formulations and monitoring their activity during treatment. Funding Statement: The research was supported by FIPE/HCPA (Fundo de Incentivo a Pesquisa e Eventos do Hospital de Clinicas de Porto Alegre). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Ethical approval to conduct this study has been granted by the Ethics Committee of Hospital de Clinicas de Porto Alegre (HCPA). Participating adults as well as those responsible for minors signed informed consents in duplicate, keeping a copy for themselves.