Frontiers in Oncology (Sep 2023)

Evaluation of factors leading to poor outcomes for pediatric acute lymphoblastic leukemia in Mexico: a multi-institutional report of 2,116 patients

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

DOI
https://doi.org/10.3389/fonc.2023.1255555
Journal volume & issue
Vol. 13

Abstract

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Background and aimsPediatric 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.MethodsPatients <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.ResultsOverall, 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 >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.ConclusionOutcomes 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.

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