Controle da contagem de leucócitos durante a manutenção definitiva como fator prognóstico na Leucemia Linfocítica Aguda da infância

Abstract

Introduction: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Chemotherapy protocols have been refined over the years to reduce relapse rates and treatment-related toxicities. While current treatment protocols include several risk stratification and prognostic factors, leukocyte count control during maintenance therapyhas not yet been established as one of them. Methods: This was an observational, analytical, and retrospective study based on the analysis of leukocyte counts during the maintenance phase of treatment in children with ALL treated at the pediatric hematology unit of IPPMG/UFRJ from 2005 to 2016. These patients were followed up, and data were collected in 2019. An index was created to quantify the daily burden of leukocyte counts exceeding 3,000/mm³ during the maintenance phase, calculated through area under the curve using triangular/trapezoidal and exponential methods. These indices were correlated with event-free survival after the start of maintenance and late relapse-free survival, and adjusted for established prognostic factors such as age at diagnosis, initial leukocyte count, and BFM risk stratification. Results: A total of 77 patients were analyzed, with a median age of 4.65 years and male predominance (57.1%). Most patients had Bcell ALL (84.4%) and an initial leukocyte count below 50,000/mm³ (79.2%). According to the BFM protocol, 33.8% were classified as high risk, 40.2% as intermediate risk, and 26,0% as low risk. During follow-up, 24.7% relapsed, 13% died, and 5.2% underwent hematopoietic stem cell transplantation. A mean leukocyte count g 4,200/mm³ during the maintenance phase was associated with worse event-free survival after the start of maintenance, both when adjusted for age and initial leukocyte count (HR 3.93; 95% CI 1.09314.17; p = 0.04), and when adjusted for risk group (HR 3.96; 95% CI 1.08314.52; p = 0.04). It was also associated with a higher risk of late relapse when adjusted for age and initial leukocyte count (HR 4.41; 95% CI 1.05318.48; p = 0.04), and showed a trend toward significance when adjusted for risk (HR 3.94; 95% CI 0.99315.61;p=0.06). Conclusion: A mean leukocyte count g 4.200/mm³ during maintenance was associated with increased risk of post maintenance events and late relapse and may serve as an important therapeutic guide during this phase of treatment.