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

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

ANÁLISIS DE LA EXPRESIÓN DE LOS ANTÍGENOS TESTICULARES DE CÁNCER EN LEUCEMIA MIELOIDE CRÓNICA

Los antígenos testiculares de cáncer (ATC) están expresados en diversos cánceres, pero no en tejido adulto normal, con excepción de células germinales de testículo, por esta característica son considerados como blancos para inmunoterapia. El objetivo de este trabajo fue estudiar el papel de estos ATC en inmunoterapia y la relación entre su expresión y el comportamiento biológico en leucemia mieloide crónica (LMC). Se identificaron 8 ATC (MAGE-A3, MAGE-A4, MAGE-B2 MAGE-C1, BAGE-1, GAGE-2, LAGE-1 and NY-ESO-1) en 8 líneas celulares hematológicas (K562, HL-60, Molt-4, Reh, Jurkat, Raji, Ramos, U-937), 10 muestras de médula ósea (MO) de individuos sanos y 65 muestras de MO de pacientes con LMC, mediante reacción en cadena de la polimerasa por transcriptasa reversa (RT-PCR) y Western-blot. En líneas celulares se detectó expresión de los ATC, la cual fue nula en individuos sanos. K562 expresó los 8 HL-60: MAGE-A3, MAGE-B2 y GAGE-2, en Reh: MAGE-A3, en U-937: GAGE-2, las 4 líneas restantes no expresaron ninguno de los ATC. Las frecuencias en los pacientes con LMC fueron: MAGE-A3 32,3%, MAGE-B2 1,5%, MAGE-C1 3,0%, MAGE-A4 63,6%, BAGE-1 6,6%, GAGE-2 20,0%, LAGE-1 13,3% y NY-ESO-1 36,6%. La correlación entre la expresión de los genes y los parámetros clinicopatológicos fue, MAGE-A3 en sexo con una p=0,018, MAGE-C1: leucocitos p=0,014 y plaquetas p=0,002 y finalmente LAGE-1 plaquetas p=0,001. Se detectó la proteína MAGE-A3 en los pacientes positivos a nivel de mRNA. .Además, se analizaron 10 muestras de pacientes bajo tratamientos convencionales (Hidroxiurea e interferon alfa) y 13 con inhibidores de tirosina cinasa (Imatinib, Nilotibib, Dasatinib). Había una expresión aumentada para ambos tratamientos de MAGE-A3, en inhibidores de tirosina cinasa 69,2% y convencionales 50,0%, de MAGE-A4 53,8% y 20,0%, NY-ESO-1 0% y 20,0% respectivamente. Los ATC podían utilizarse como antígenos específicos en inmunoterapia en LMC, siendo de gran importancia en enfermedad la mínima residual y en aquellos pacientes que son resistentes a la quimioterapia

Frequency and clinical association of NY-ESO-1 gene expression in diffuse large B-cell lymphoma

Objective: Our objective was to evaluate the frequency of expression and determine the expression levels of the NY-ESO-1 gene in patients with DLBCL as well as to examine its relationship with clinical parameters and survival. Methods: We analyzed NY-ESO-1 gene expression levels using real-time quantitative RT-PCR (RT-qPCR) in 112 patients with DLBCL. The associations between the expression of the NY-ESO-1 gene and the clinical variables were evaluated using the Chi-square test and Fisher’s exact test. Overall survival (OS) was determined using the Kaplan–Meier method. Result: The results showed that the NY-ESO-1 gene was expressed in 46.4% (52/112) of patients with DLBCL, and NY-ESO-1 gene expression was associated with clinical parameters such as LDH, clinical stage, and International Prognostic Index (IPI) (p ≤ 0.05). High levels of NY-ESO-1 gene expression were associated with advanced disease stages, and the survival rates after 5.3 years of tracking were lower in the patients expressing the NY-ESO-1 gene (66.4%) than in those not expressing the gene (23.1%). Conclusion: The expression levels of the NY-ESO-1 gene in patients with DLBCL may be of great utility for diagnosing and determining the prognosis of this disease