A Latin American consensus on the use of L-asparaginase in pediatric and adolescent/young adult acute lymphoblastic leukemia – part 1

Background L-asparaginase remains a fundamental component of curative therapy for children, adolescents and young adults (AYA; 15–39 years) with acute lymphoblastic leukemia (ALL). However, optimal treatment remains challenging across Latin America due to shortages, heterogeneous product quality, limited access to therapeutic drug monitoring (TDM), and toxicities. This study aimed to develop regionally adapted, evidence-informed recommendations for L-asparaginase use in ALL. Methods A multinational modified Delphi process involved 19 experts from 10 Latin American countries. Following a literature review, candidate statements were developed. Consensus was predefined as ≥80% of respondents assigning scores of 7–9 on a 9-point Likert scale. Statements not reaching consensus underwent iterative discussion, revision, and reevaluation. Results Ninety-three statements were evaluated in the first anonymous voting round and grouped post hoc into five thematic blocks; this first part reports the 46 statements of blocks 1–3: treatment continuity, pharmacokinetic and dosing principles, and TDM and treatment optimization. Round-level participation was 94.7%, 84.2%, and 84.2% in Rounds 1–3. Thirty-two statements achieved consensus in the first round. The 14 that did not were subdivided, merged, reformulated, or withdrawn, yielding 14 revised statements; six achieved consensus in the second round, one was withdrawn, and the remaining seven were consolidated into six third-round statements, all achieving consensus. The process resulted in 44 final consensus statements. Key recommendations emphasize preservation of therapeutic exposure, avoidance of unnecessary discontinuation, formulation-specific pharmacokinetics and dosing, linkage of dose and dosing intervals to the desired duration of exposure, and expansion of TDM, with serum asparaginase activity ≥0.1 IU/mL at a formulation- and schedule-appropriate sampling time endorsed as the minimum therapeutic target. Conclusions This consensus provides a multinational Latin American framework for L-asparaginase use in ALL. The recommendations support exposure-centered treatment strategies and identify priorities for regional collaboration, including pharmacokinetic monitoring, toxicity management, and access to high-quality L-asparaginases.