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

Background and aims: Pediatric 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. Methods: Patients <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. Results: Overall, 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. Conclusion: Outcomes 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.

Lanthanum delays senescence and improves postharvest quality in cut tulip (Tulipa gesneriana L.) flowers.

We tested two sources of lanthanum (La), LaCl3 and La(NO3)3 × 6H2O at a concentration of 40 µM each, in the treatment solution of cut flowers of 15 tulip (Tulipa gesneriana L.) cultivars. Ascorbic acid (AsA; 0.2 g/L) was used as a reference solution, while distilled water was evaluated as an absolute control. With both La sources, bud length and diameter, and stem length were increased; as a result, stem curvature was also significantly increased with La treatments. The cultivars Laura Fygi and Rosario registered the highest relative stem elongation. Lalibela and Acropolis displayed the greatest stem curvature on the last day in vase. At 3, 5, 7, 9 and 11 days after cutting, the highest solution uptake was recorded in flower stems treated with LaCl3, surpassing the control by 5, 11, 15, 18 and 24%, respectively. The relative stem elongations observed were 21.3, 27.4, 35.2 and 35.5% in the control, AsA, LaCl3 and La(NO3)3, respectively. The mean solution uptake per gram of stem fresh biomass weight was 1.44, 1.44, 1.71 and 1.54 mL in the control, AsA, LaCl3 and La(NO3)3, respectively. LaCl3 significantly increased the bud length and solution uptake of flower stems, while La(NO3)3 × 6H2O increased stem fresh weight.

Lanthanum Prolongs Vase Life of Cut Tulip Flowers by Increasing Water Consumption and Concentrations of Sugars, Proteins and Chlorophylls.

We evaluated the effect of separately adding two sources of lanthanum (La), LaCl3 and La(NO3)3 × 6H2O at a concentration of 40 µM each, to the preservative solution of 15 cut tulip flower varieties. Ascorbic acid (AsA; 0.2 g/L) was used as a reference solution, while distilled water was used as control. The variety Laura Fygi recorded the longest vase life with 13 days. The highest water consumption per gram of stem fresh biomass weight (FBW) (2.5 mL) was observed in the variety Violet Beauty, whereas the lowest (1.098 mL) was recorded in Pink Impression. At the end of the vase life period, higher concentrations of total soluble sugars in petals and total soluble proteins in leaves were recorded in La-treated stems, compared to the AsA treatment and the control. Additionally, La(NO3)3 × 6H2O supply increased the fresh weight of stems in vase and prolonged vase life. Moreover, this treatment resulted in the highest foliar concentration of chlorophylls at the end of vase life. Therefore, La increases tulip flower vase life as a consequence of improving the concentrations of some vital biomolecules.

Endoscopic Ultrasound in Pediatric Patients With Pancreatobiliary Disease.

BACKGROUND: Endoscopic ultrasound (EUS) is one of the greatest advances of the last few decades for the diagnostic and therapeutic approach of gastrointestinal diseases in adults. However, there are limitations to the application of the procedure in the pediatric population. The aim of this study was to describe the diagnostic yield and therapeutic role of EUS in pediatric patients with pancreatobiliary disease. MATERIALS AND METHODS: A retrospective study was performed on a prospective database of pediatric patients who underwent diagnostic and therapeutic endosonographic procedures. All patients seen in a 12-year period were included. RESULTS: A total of 54 patients were included, including 32 (59.3%) female individuals, with an average age of 16 (9 to 17) years. EUS was abnormal in 46 (85%) patients. Of the abnormal procedures, 4 (7.4%) corresponded to therapeutic ones. The main indication of the study was recurrent acute pancreatitis in 29 (54%). The main endosonographic findings were microlithiasis in 14 (25.9%), chronic pancreatitis in 9 (16.7%), and pancreatic tumors in 6 (11.1%) patients. Follow-up was performed in 31 (57.4%) patients, 19/31 patients underwent surgery, and 4/31 patients had endoscopic retrograde cholangiopancreatography. The median follow-up was 910 (2 to 3916) days. In 100% of the patients with follow-up, the initial diagnosis of EUS was confirmed. CONCLUSION: EUS is a useful and safe tool in the pediatric population with pancreatobiliary diseases.

Variants in ARID5B gene are associated with the development of acute lymphoblastic leukemia in Mexican children.

A high impact of ARID5B SNPs on acute lymphoblastic leukemia (ALL) susceptibility has been described in Hispanic children; therefore, it is relevant to know if they influence the high incidence of childhood-ALL in Mexicans. Seven SNPs (rs10821936, rs10994982, rs7089424, rs2393732, rs2393782, rs2893881, rs4948488) of ARID5B were analyzed in 384 controls and 298 ALL children using genomic DNA and TaqMan probes. The SNPs were analyzed for deviation of Hardy-Weinberg equilibrium; Fisher's exact test was used to compare the genotypic and allelic frequencies between controls and patients. The association between SNPs and ALL susceptibility was calculated, and haplotype and ancestry analyses were conducted. All SNPs were associated with ALL, pre-B ALL, and hyperdiploid-ALL susceptibility (p < 0.05). No association with T-ALL and gene fusions was found (p > 0.05). The seven SNPs were associated with risk of pre-B ALL in younger children; however, rs2393732, rs2393782, rs2893881, and rs4948488 were not associated with susceptibility in older children and adolescents. The CAG haplotype (rs10821936, rs10994982, rs7089424) was strongly associated with ALL risk in our population (p < 0.00001). The frequency of all risk alleles in our ALL, pre-B, and hyperdiploid-ALL patients was higher than that in Hispanic children reported. This is the first report showing the association between rs2393732, rs2393782, and rs4948488 with pre-B hyperdiploid-ALL children. The G allele at rs2893881 confers major risk for pre-B hyperdiploid-ALL in Mexican (OR, 2.29) than in Hispanic children (OR, 1.71). The genetic background of our population could influence the susceptibility to ALL and explain its high incidence in Mexico.