Childhood acute lymphoblastic leukemia survival and spatial analysis of socio-environmental risks in Mexico.

Background: Acute lymphoblastic leukemia (ALL) etiology remains largely unknown; incidence patterns by age, sex, and geographical distribution suggest a potential environmental role. Aim: To identify ALL clusters from four contrasting urban areas of Mexico and to characterize the sources of environmental carcinogens. Methods: Hospital-based ALL cases (n = 443) diagnosed in children <19 years old from the Metropolitan Zones of Merida and San Luis Potosi, the State of Mexico, and Tijuana were analyzed (2015-2020). ALL cases were coded according to the International Classification of Diseases for Oncology. ALL clusters were identified by Kernel Density, and excess risk was estimated. Data of particulate matter ≤2.5 µm (PM2.5) concentrations measured by community-monitoring stations were analyzed. Geocoded datasets of benzene, polycyclic aromatic hydrocarbons, and PM2.5 sources were analyzed to characterize patterns of exposure in ALL clusters. Results: The survival rate for ALL ranged from 61.5% to 78.6%. Seven ALL clusters with excess risk (RR 1.4-2.3, p < 0.05) were identified. The carcinogen sources included artisanal brick kilns, gas stations, cement works, carpentry, paint, and chemical manufacturing establishments. PM2.5 levels ranged from 15 µg/m3 to 37 µg/m3 among study areas. Conclusion: ALL clusters were identified at the community level; the excess risk could be explained by small-scale carcinogen sources. The levels of PM2.5 in outdoor air ranged from 3 to 6 times above the World Health Organization (WHO) air quality guidelines. Healthcare providers must raise awareness of the increased risk of ALL in children living near sources of environmental carcinogens; cancer control and prevention strategies must be steered from a multi-sectoral and multi-action perspective to protect children's health.

Securing access to a comprehensive diagnostic panel for children with suspected acute lymphoblastic leukemia: Results from the Mexico in Alliance with St. Jude "Bridge Project".

Background: The "Bridge Project" is a Mexico in Alliance with St. Jude (MAS) initiative developed in 2019 to improve access, accuracy, and timeliness of specialized diagnostic studies for patients with suspected acute lymphoblastic leukemia (ALL). The project strategy relies on service centralization to improve service delivery, biological characterization, risk-group classification, and support proper treatment allocation. Methods: This is an ongoing prospective multisite intersectoral quality improvement (QI) project available to all patients 0-18 years of age presenting with suspected ALL to the 14 actively participating institutions in 12 Mexican states. Institutions send specimens to one centralized laboratory. From a clinical standpoint, the project secures access to a consensus-derived comprehensive diagnostic panel. From a service delivery standpoint, we assess equity, timeliness, effectiveness, and patient-centeredness. From an implementation science standpoint, we document feasibility, utility, and appropriateness of the diagnostic panel and centralized approach. This analysis spans from July 2019 to June 2023. Results: 612 patients have accessed the project. The median age was 6 years (IQR 3-11), and 53% were males. 94% of the specimens arrived within 48 hours, which documents the feasibility of the centralized model, and 100% of the patients received precise and timely diagnostic results, which documents the effectiveness of the approach. Of 505 (82.5%) patients with confirmed ALL, 463/505 (91.6%) had B-cell ALL, and 42/505 (8.3%) had T-cell ALL. High-hyperdiploidy was detected by DNA index in 36.6% and hypodiploidy in 1.6%. 76.6% of the patients had conclusive karyotype results. FISH studies showed t(12;21) in 15%, iAMP21 in 8.5%, t(1;19) in 7.5%, t(4;11) in 4.2%, t(9;22) in 3.2%, del(9)(p21) in 1.8%, and TRA/D (14)(q11.2) rearrangement in 2.4%. Among B-cell ALL patients, 344/403 (85.1%) had Day 15 MRD<1% and 261/305 (85.6%) Day 84 MRD<0.01. For T-cell ALL patients 20/28 (71.4%) had Day 29 MRD<0.01% and 19/22 (86.4%) Day 84 MRD<0.01%. Conclusions: By securing access to a standardized consensus-derived diagnostic panel, the Bridge Project has allowed better characterization of childhood ALL in Mexico while producing unprecedented service improvements and documenting key implementation outcomes. We are using these results to inform iterative changes to the diagnostic panel and an associated treatment guideline (MAS-ALL18).

Pediatric mature B-cell NHL, early referral and supportive care problems in a developing country.

OBJECTIVE: Mature B-cell non-Hodgkin lymphoma (B-NHL) comprises more than 50% of all non-Hodgkin lymphoma (NHL) in children and adolescents. An official report published by the Mexican National Center for the Control and Prevention of Cancer in the Pediatric and Adolescent Populations, reported a lymphoma OS of 71% (including all Hodgkin and NHL). The Mexican Association of Pediatric Oncology and Hematology conducted a retrospective study to analyze the clinical characteristics and outcomes of children with diagnosis of B-NHL in Mexico, in order to perceive the main areas of improvement in the health care. METHODS: From 1 January 2000 to 31 December 2016, 166 pediatric patients were diagnosed with B-cell NHL at the participant institutions. RESULTS: According to histology the outcomes were 5-year EFS 63%, for BL/BLL, and 80% DLBCL, (P = .051), 5-year PFS 81%, for BL/BLL, and 91% for DLBCL, (P = .126), and 5-year OS 71%, for BL/BLL, and 83% for DLBCL, (P = .095). DISCUSSION: Overall, 18 patients died due to acute treatment toxicity, resulting in a cumulative incidence of toxic death of 10.84% and an early death rate of 7.23%, defined as <30 days after initial treatment. In conclusion, there is an urgent need to establish an academic collaboration to create strategies to improve pediatric cancer care according to our resources, especially in diseases with expected excellent prognosis as B-NHL. These strategies must include comprehensive supportive care, early referral, and the creation of easy communication between pediatric and adults centers as well as late-effects clinics.

Analysis of Thiopurine S-Methyltransferase Deficient Alleles in Acute Lymphoblastic Leukemia Patients in Mexican Patients.

BACKGROUND AND AIMS: It has been demonstrated that heterozygote and homozygote thiopurine S-methyltransferase (TPMT) mutant allele carriers are at high risk to develop severe and potentially fatal hematopoietic toxicity after treatment with standard doses of 6-mercaptopurine (6-MP) and methotrexate (MX). Those drugs are the backbone of acute lymphoblastic leukemia (ALL) and several autoimmune disease treatments. We undertook this study to determine the frequency of the TPMT deficient alleles in children with ALL and non-ALL subjects from Mexico City and Yucatan, Mexico. METHODS: We included 849 unrelated subjects, of which 368 ALL children and 342 non-ALL subjects were from Mexico City, and 60 ALL cases and 79 non-ALL individuals were from Yucatan. Genotyping of the rs1800462, rs1800460 and rs1142345 SNPs was performed by 5'exonuclease technique using TaqMan probes (Life Technologies Foster City, CA). RESULTS: The mutant TPMT alleles were present in 4.8% (81/1698 chromosomes) and only 0.2% were homozygote TPMT*3A/TPMT*3A. We did not find statistically significant differences in the distribution of the mutant alleles between patients from Mexico City and Yucatan in either ALL cases or non-ALL. Nonetheless, the TPMT*3C frequency in ALL patients was higher than non-ALL subjects (p = 0.03). To note, the null homozygous TPMT*3A/TPMT*3A genotype was found in 2.5% of the non-ALL subjects. CONCLUSIONS: TPMT mutant alleles did not exhibit differential distribution between both evaluated populations; however, TPMT*3C is overrepresented in ALL cases in comparison with non-ALL group. Assessing the TPMT mutant alleles could benefit the ALL children and those undergoing 6-MP and MX treatment.