Alfaro-Hernández Laura, Ramírez-Ramírez Dalia, Romo-Rodríguez Rubí, Ayala-Contreras Karen, Del Campo-Martínez Ángeles, López-Aguilar Enrique, Flores Lujano Janet, Allende-López Aldo, Alarcón-Ruiz Erika, Banos-Lara Ma Del Rocio, Casique-Aguirre Diana, Elizarrarás-Rivas Jesús, López-Aquino Javier Antonio, Garrido-Hernández Miguel Ángel, Olvera-Caraza Daniela, Terán-Cerqueda Vanessa, Solís-Poblano Juan Carlos, Aristil-Chery Pierre Mitchel, Alvarez-Rodríguez Enoch, Herrera-Olivares Wilfrido, Chavez-Aguilar Lénica Anahí, Márquez-Toledo Aquilino, Cano-Cuapio Lena Sarahi, Luna-Silva Nuria Citlalli, Martínez-Martell Maria Angélica, Ramirez-Ramirez Anabel Beatriz, Rodríguez-Espinosa Juan Carlos, Medina-León Daniela, Rodríguez-Díaz Roberto, Mata-Rocha Minerva, Olivares-Sosa Amanda Idaric, Rosas-Vargas Haydeé, Mejia-Arangure Juan Manuel, Millán-Pérez-Peña Lourdes, Pelayo Rosana, Núñez-Enríquez Juan Carlos
Laboratorio de Citómica del Cáncer Infantil, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, Mexico.
Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico.
Front Oncol. 2025 Jul 28;15:1614445. doi: 10.3389/fonc.2025.1614445. eCollection 2025.
Despite high cure rates for pediatric B-cell acute lymphoblastic leukemia (B-ALL) in high-income countries, early mortality remains unacceptably high in low- and middle-income countries (LMICs), largely due to limited access to risk-adapted therapy and response monitoring. Southern Mexico, a region marked by socioeconomic vulnerability, is emblematic of this disparity. In 2022 the Childhood Cancer Cytomics Laboratory (CCCL) started the implementation of standardized protocols for immunophenotyping and measurable residual disease (MRD) monitoring of B-ALL patients from this region.
To evaluate the impact of implementing standardized immunophenotyping and MRD monitoring on early mortality in children with B-ALL treated in public hospitals in southern Mexico.
A prospective cohort study was conducted between 2022 and 2024. Before initiating CCCL activities, public hospitals were invited to participate, and standardized protocols for sample collection, handling, and transportation were implemented across all participating sites. A total of 298 children newly diagnosed with B-ALL were enrolled and followed throughout treatment. Patients were stratified based on whether immunophenotyping and MRD monitoring were performed at the CCCL. MRD was assessed at the end of induction (EOI) therapy using standardized EuroFlow-based flow cytometry protocols. Simultaneously, early mortality-defined as death occurring within the first year after diagnosis-was evaluated. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were estimated using multivariable Cox regression, with p-values < 0.05 considered statistically significant.
Early mortality was significantly lower among patients who underwent MRD monitoring at the CCCL (10.8%) compared to those who did not (24.8%, p<0.01). One-year overall survival was also higher in patients evaluated at the CCCL (89.6% . 75.2%, p<0.001). In the multivariable Cox regression analysis, patients who underwent MRD monitoring at the CCCL showed a significantly lower risk of early mortality during the first year of treatment (adjusted hazard ratio [aHR] 0.41; 95% CI: 0.22-0.77; p < 0.01), after adjusting for sex, NCI risk classification, treatment abandonment, and early relapse. MRD positivity was associated with a CD34 ProB immunophenotype, suggesting a more treatment-resistant leukemic profile.
Centralized, standardized MRD monitoring at the CCCL was associated with a reduction in early mortality and improved one-year survival in children with B-ALL from a socioeconomically vulnerable population. These findings demonstrate the clinical value and feasibility of implementing MRD-informed response assessment in LMICs and highlight the potential of centralized diagnostic platforms to reduce survival disparities in childhood leukemia.
尽管高收入国家儿童B细胞急性淋巴细胞白血病（B-ALL）的治愈率很高，但在低收入和中等收入国家（LMICs），早期死亡率仍然高得令人无法接受，这主要是由于获得风险适应性治疗和反应监测的机会有限。墨西哥南部是一个社会经济脆弱的地区，是这种差异的典型代表。2022年，儿童癌症细胞组学实验室（CCCL）开始对该地区B-ALL患者实施免疫表型分析和可测量残留病（MRD）监测的标准化方案。
评估实施标准化免疫表型分析和MRD监测对墨西哥南部公立医院治疗的B-ALL儿童早期死亡率的影响。
在2022年至2024年期间进行了一项前瞻性队列研究。在CCCL活动开始前，邀请公立医院参与，并在所有参与地点实施样本采集、处理和运输的标准化方案。共有298名新诊断为B-ALL的儿童入组并在整个治疗过程中进行随访。患者根据是否在CCCL进行免疫表型分析和MRD监测进行分层。在诱导治疗结束时（EOI），使用基于标准化EuroFlow的流式细胞术方案评估MRD。同时，评估早期死亡率，即诊断后第一年内发生的死亡。使用多变量Cox回归估计调整后的风险比（aHR）和95%置信区间（CI），p值<0.05被认为具有统计学意义。
与未在CCCL进行MRD监测的患者（24.8%）相比，在CCCL进行MRD监测的患者早期死亡率显著降低（10.8%，p<0.01）。在CCCL接受评估的患者一年总生存率也更高（89.6%对75.2%，p<0.001）。在多变量Cox回归分析中，在CCCL进行MRD监测的患者在治疗的第一年早期死亡风险显著降低（调整后的风险比[aHR]为0.41；95%CI：0.22-0.77；p<0.01），在调整了性别、NCI风险分类、治疗放弃和早期复发后。MRD阳性与CD34 ProB免疫表型相关，提示白血病谱更具治疗抗性。
CCCL的集中化、标准化MRD监测与社会经济弱势群体中B-ALL儿童的早期死亡率降低和一年生存率提高相关。这些发现证明了在LMICs中实施基于MRD的反应评估的临床价值和可行性，并突出了集中化诊断平台在减少儿童白血病生存差异方面的潜力。
