Evaluation of factors leading to poor outcomes for pediatric acute lymphoblastic leukemia in Mexico: a multi-institutional report of 2,116 patients
Authors: Moreira Daniel C. , González-Ramella Oscar , Echavarría Valenzuela Maite , Carrillo Angela K. , Faughnan Lane , Job Godwin , Chen Yichen , Villegas Cesar , Ellis Irigoyen Andrea , Barra Urbays Rosario , Ramírez Martinez Maribel , Altamirano Alvarez Eduardo , León Espitia José Antonio , López Facundo Norma Araceli , Colunga Pedraza Julia Esther , Reyes Gutierrez Flor de María , Aguilar Román Ana Berenice , Tamez Gómez Edna Liliana , Portillo Zavala Claudia Selene , Negroe Ocampo Natalia del Carmen , Pulido Sanchez Sandra Guadalupe , Cortés Alva Deyanira , Casillas Toral Paola , Salas Villa Karime , Mendoza Sánchez Patricia Judith , Pérez Alvarado Carlos , Tamayo Pedraza Gabriela , González Zamorano Margarita , Ávila Alba José Manuel Ricardo , Becerril Becerril Jocelyn , Ramírez Durán Hernán , Sandoval Cabrera Antonio , Pineda Gordillo Adolfo , de la Rosa Alonso Dora Iveth , Mejía Marín Leonardo Javier , Benítez Can Leslie de los Ángeles , Gutiérrez Martinez Itzel , Jiménez Osorio Mariana Isabel , Echeandia Naomi , Casillas Erika , Guerrero-Gomez Karla , Devidas Meenakshi , Friedrich Paola 
Published: September 2023

Background and aims

Pediatric acute lymphoblastic leukemia (ALL) survival rates in low- and middle-income countries are lower due to deficiencies in multilevel factors, including access to timely diagnosis, risk-stratified therapy, and comprehensive supportive care. This retrospective study aimed to analyze outcomes for pediatric ALL at 16 centers in Mexico.

Methods

Patients &lt;18 years of age with newly diagnosed B- and T-cell ALL treated between January 2011 and December 2019 were included. Clinical and biological characteristics and their association with outcomes were examined.

Results

Overall, 2,116 patients with a median age of 6.3 years were included. B-cell immunophenotype was identified in 1,889 (89.3%) patients. The median white blood cells at diagnosis were 11.2.5 × 103/mm3. CNS-1 status was reported in 1,810 (85.5%), CNS-2 in 67 (3.2%), and CNS-3 in 61 (2.9%). A total of 1,488 patients (70.4%) were classified as high-risk at diagnosis. However, in 52.5% (991/1,889) of patients with B-cell ALL, the reported risk group did not match the calculated risk group allocation based on National Cancer Institute (NCI) criteria. Fluorescence in situ hybridization (FISH) and PCR tests were performed for 407 (19.2%) and 736 (34.8%) patients, respectively. Minimal residual disease (MRD) during induction was performed in 1,158 patients (54.7%). The median follow-up was 3.7 years. During induction, 191 patients died (9.1%), and 45 patients (2.1%) experienced induction failure. A total of 365 deaths (17.3%) occurred, including 174 deaths after remission. Six percent (176) of patients abandoned treatment. The 5-year event-free survival (EFS) was 58.9% ± 1.7% for B-cell ALL and 47.4% ± 5.9% for T-cell ALL, while the 5-year overall survival (OS) was 67.5% ± 1.6% for B-cell ALL and 54.3% ± 0.6% for T-cell ALL. The 5-year cumulative incidence of central nervous system (CNS) relapse was 5.5% ± 0.6%. For the whole cohort, significantly higher outcomes were seen for patients aged 1–10 years, with DNA index &gt;0.9, with hyperdiploid ALL, and without substantial treatment modifications. In multivariable analyses, age and Day 15 MRD continued to have a significant effect on EFS.

Conclusion

Outcomes in this multi-institutional cohort describe poor outcomes, influenced by incomplete and inconsistent risk stratification, early toxic death, high on-treatment mortality, and high CNS relapse rate. Adopting comprehensive risk-stratification strategies, evidence-informed de-intensification for favorable-risk patients and optimized supportive care could improve outcomes.