Acute leukemia is the leading cause of death in children worldwide, particularly in developing countries where the growing number of cases with unfavorable prognosis and high risk of early relapse have positioned pediatric cancer as a priority. The late and imprecise diagnosis, malnutrition and unfavorable environmental conditions, and toxicity-associated therapy are some of the factors that compromise the success of the treatment and affect survival rates in vulnerable regions. An early and exhaustive classification of malignant neoplasms at the clinical debut and the proper follow-up of treatment's response constitute one of the most powerful prognostic factors. Remarkably, the ultrasensitive detection of residual and relapse clones that determine the minimal/measurable residual disease (MRD) has been a milestone in the comprehensive management of hematologic malignancies that favorably improve the complete remission cases. In this review, we discuss the scientific and technological advances applied to laboratory diagnosis in MRD determination: from the multiparametric immunophenotyping to next-generation sequencing and cytomics. As a result of multidisciplinary research in the main concentration oncology centers and laboratories, residual leukemia detection strategies that combine molecular analysis and cellular markers are recommended as the most valuable tools, making them the paradigm for stratification campaigns in vulnerable regions.
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