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).

Geographical Distribution and Cluster Detection of Childhood Leukemia in the Metropolitan Area of Guadalajara, Mexico.

BACKGROUND: Acute leukemia is the most common cancer in childhood. Analyzing the spatial distribution of acute leukemia may generate the identification of risk factors. OBJECTIVE: To study the incidence rate of acute leukemia, its geographic distribution, and cluster detection in the metropolitan area of Guadalajara, Mexico. METHODS: We included children under 15 years of age diagnosed with acute leukemia during the period 2010-2014 in the metropolitan area of Guadalajara. Each case was geo-referenced to street level to latitude and longitude coordinates using Quantum Geographic Information System (QGIS). Spatial clusters were found in the location of the acute leukemia cases applying the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm with R statistical software. RESULTS: A total of 269 cases of leukemia were registered, 227 (84%) were acute lymphoblastic leukemia and 42 (16%) acute myeloblastic leukemia. The mean age was 6 ± 4 years. The mean incidence of acute leukemia was 6.44 cases/100,000 inhabitants: El Salto 10.12/100,000, Guadalajara 7.55/100,000, and Tlaquepaque 6.74/100,000. The DBSCAN found three clusters, all located within the municipality of Guadalajara. CONCLUSIONS: The incidence of acute leukemia in our population is higher than that in Canada and the USA. We found three spatial clusters of childhood acute lymphoblastic leukemia in the municipality of Guadalajara, suggesting the presence of local predisposing factors.

Secondary malnutrition and overweight in a pediatric referral hospital: associated factors.

OBJECTIVES: To establish the prevalence and identify the clinical and sociodemographic factors associated with malnutrition and overweight in a pediatric referral hospital. PATIENTS AND METHODS: We studied a cross-sectional, random sample from a pediatric hospital. Malnutrition was defined as acute when the z score of weight/height was less than -2.0 and as chronic if in addition the height/age z score was less than -2.0. Overweight risk was defined as a body mass index percentile between 85 and 94, and overweight as a body mass index percentile of 95 or higher. RESULTS: The study included 641 patients, with mean age 7.1 +/- 4.9 years (56% male). The overall prevalence of acute malnutrition was 8% and chronic malnutrition 17.0%. Overweight risk was present in 15.4% and overweight in 12.2%. Acute malnutrition was predicted by conditions on admission (hospitalization: odds ratio [OR] 2.3, confidence interval [CI] 1.3-4.3; nonsurgical subspecialty: OR 2.1, CI 1.0-4.3) and number of siblings (1 child, single mother: OR 2.6, CI 1.3-5.0). Chronic malnutrition was predicted by age (infants vs preschoolers: OR 2.0, CI 1.1-3.6; infants vs school children: OR 3.1, CI 1.8-5.5) and illness duration (>30 days: OR 2, CI 1.1-3.7). Overweight risk was associated with age (>36 months: OR 2.0, CI 1.6-3.4) and the father's educational level (college and university: OR 2.3, CI 1.3-4.3). Overweight was predicted by sex (boys: OR 2.0, CI 1.0-3.6) and age (>36 months: OR 1.7, CI 1.0-2.8). CONCLUSIONS: Overweight was as prevalent as malnutrition. Malnutrition was associated with clinical condition, age, family size, and illness duration, whereas overweight was related to age, sex, and father's education. Overweight appears as a novel finding in the nutritional profile of pediatric referral hospitals in Mexico.

Preirradiation ifosfamide, carboplatin and etoposide (ICE) for the treatment of high-grade astrocytomas in children.

BACKGROUND: Astrocytomas are the most common form of primary intracranial tumor; however, survival of patients with high-grade tumors has not changed much compared with that reported in the early 1970s. OBJECTIVE. Our objective was to assess the efficacy, security, and survival rate of postoperative chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) in pediatric patients with anaplastic astrocytomas (AA) and glioblastoma multiforme (GM). METHODS: In a phase II study, we evaluated 25 children with AA or GM. The proposed treatment was four courses of chemotherapy with ICE followed by hyperfractionated radiotherapy, and then four more courses of ICE. Patients were evaluated using MRI after surgery, after the second course of chemotherapy, and again after the last. Toxicity was determined before each course. RESULTS: The overall and disease-free survival at 60 months was 67% and 56% respectively. For supratentorial localization it was 92% at 60 months and 20% at 18 months for brain stem tumors. Fourteen patients had a complete response and 9 died as a result of tumor progression. CONCLUSIONS: Postoperative chemotherapy with ICE reduces the tumor size and increases the survival rate of pediatric patients with malignant astrocytomas with minimal toxicity.