RESUMO
The introduction of all-trans retinoic acid (ATRA) combined with anthracyclines has significantly improved the outcomes for patients with acute promyelocytic leukemia (APL), and this strategy remains the standard of care in countries where arsenic trioxide is not affordable. However, data from national registries and real-world databases indicate that low- and middle-income countries (LMIC) still face disappointing results, mainly due to high induction mortality and suboptimal management of complications. The American Society of Hematology established the International Consortium on Acute Leukemias (ICAL) to address this challenge through international clinical networking. Here, we present the findings from the ICAPL study involving 806 patients with APL recruited in Brazil, Chile, Paraguay, Peru, and Uruguay. The induction mortality rate has decreased to 14.6% compared to the pre-ICAL rate of 32%. Multivariable logistic regression analysis revealed as factors associated with induction death: age ≥ 40 years, ECOG = 3, high-risk status based on the PETHEMA/GIMEMA classification, albumin level ≤ 3.5 g/dL, bcr3 PML/RARA isoform, the interval between presenting symptoms to diagnosis exceeding 48 hours, and the occurrence of central nervous system and pulmonary bleeding. With a median follow-up of 53 months, the estimated 4-year overall survival (OS) rate is 81%, the 4-year disease-free survival (DFS) rate is 80%, and the 4-year cumulative incidence of relapse (CIR) rate is 15%. These results parallel those observed in studies conducted in high-income countries, highlighting the long-term effectiveness of developing clinical networks to improve clinical care and infrastructure in LMIC.
RESUMO
La evaluación genética en los niños con Leucemia Linfática Aguda (LLA) constituye actualmente un punto fundamental para una adecuada estratificación de riesgo de la enfermedad, y por tanto, para direccionar la intensidad del tratamiento de la misma. Es necesario conocer si las alteraciones genéticas en nuestra población son similares a las de otras realidades, para según esto poder adecuar nuestro tratamiento de acuerdo al perfil genético. El estudio solo incluye los resultados de cariotipo convencional en nuestra población pediátrica con LLA, encontrándose una cifra mayor de pacientes con cariotipo normal, debido a que no se han realizado pruebas más avanzadas para búsqueda de alteración como la t(12;21), entre otras. Tenemos un porcentaje similar a la literatura mundial de pacientes con hiperdiploidías, y se corrobora su buen pronóstico, sobre todo en aquellos con hiperdiploidías altas. Tendencia similar se observó en aquellos con pseudodiploidías. La cifra de pacientes con t(9;22) fue similar a lo reportado, y se evidenciaron sus características de mal pronóstico conocidas. Otros hallazgos se encuentran en números escasos para un análisis más profundo. Es sumamente necesario contar con técnicas actuales de evaluación de los parámetros genéticos en nuestra población para una adecuada estratificación de riesgos en nuestros pacientes, y así realizar terapias más dirigidas según estos hallazgos. Se debe continuar con los estudios de cariotipo convencional dentro de la evaluación de nuestros pacientes con LLA.
The genetic evaluation in children with Acute Lymphatic Leukemia (ALL) is a key point for accurate stratification of disease risk, and therefore to address the intensity of treatment. It is necessary to know whether the genetic alterations in our population are similar to those reported in other studies, so that our treatment can be directed to the genetic profile found. This study only includes the results of conventional karyotype in our pediatric population with ALL. It found a higher number of patients with normal karyotype, because no tests have been performed for more sofisticated search of alterations such as the t(12,21), among others. We have asimilar percentage of patients with hyperdiploidy as reported in the literature, and also confirms its good prognosis, especially in those with high hyperdiploidy, similar trend was observed in those with pseudodiploidies. The number of patients with t(9,22) were similar to those reported, and showed the well-known features of poor prognosis. Other findings are in small numbers that do not allow further analysis. It is extremely necessary to have current technical evaluation of genetic parameters in our population for adequate risk stratification in our patients, and thus make more targeted therapies according to these findings. We must continue with the conventional karyotype studies in the evaluation of our patients with ALL.
