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Background: Previous studies have shown continuous improved overall survival (OS) up to 2015 for young adults with acute lymphoblastic leukaemia (ALL). However, recently several important advances have been made justifying a more contemporary analysis of outcomes in adult with ALL., Methods: In this nationwide population-based cohort study, we included patients above 18 years of age diagnosed with ALL between January 1, 1998, and December 31, 2020. Patients were followed until December 31, 2022. By employing flexible parametric survival models, we quantified progress in OS using the key endpoint of 2-year age standardized OS for all patients and clinical subgroups of interest., Findings: This study includes 657 patients and demonstrates a significant improvement in OS over time with the 2-year age standardized OS increasing from 36·4 % (95 % CI, 27·0-45·8 %) for patients diagnosed in 1998 to 68·6 % (95 % CI, 60·2-76·9)for patients diagnosed in 2020, corresponding to an absolute increase in 2-year OS of 32·2 % points (95 % CI, 19·1-45·2). Stratified analysis revealed improvements for both Philadelphia chromosome positive and negative ALL, across cytogenetic risk groups, and for B- and T-cell ALL, whereas the latter did not reach statistical significance. Improvements were seen across all ages; however, most pronounced for Philadelphia chromosome positive ALL and patients below 60 years of age., Interpretation: These results show a universal and continuous improvement in the treatment of adult ALL. Currently, novel treatment combination and advances in cellular therapy occur rapidly, and we expect even further improvements in the years to come., Funding: Northern Region of Denmark., Competing Interests: Declaration of Competing Interest D.T.K: Consulting/advisory board: AbbVie, Atheneum, Astellas Pharma (non-related, potential); A.S.R: Consulting fees: AbbVie. Travel grant; Jazz Pharmaceuticals (non-related, potential). Other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The present study aims to provide outcome data in children with relapsed acute lymphoblastic leukemia (ALL) over two decades and variables that impact survival., Method: This retrospective study included children who were diagnosed with ALL and treated at our center and relapsed between March 2002 and March 2021., Results: A total of 100 children (64 boys, 36 girls) were included; 80 had B-ALL, 20 had T-ALL. 50 children had a very early relapse, while 25 each had an early and late relapse. The site of relapse was bone marrow in 57, isolated central nervous system (CNS) in 10, isolated testicular in 1, and combined bone marrow and CNS relapse in 32 children. Thirty-six families opted for the best supportive care; 23 of these had very early relapse. Among the 35 who were in remission following induction chemotherapy, 32 (91%) underwent hematopoietic stem cell transplantation (HSCT); 17/32 (53%) were alive and disease-free. Overall survival (OS) was 19 (19%) with a median follow-up of 23.5 months with a significantly improved survival post-measurable risk of disease (MRD) based risk stratification (4% vs 35%, P = 0.02). The OS with very early, early, and late relapses were 8%, 28%, and 32% (P = 0.018), and 15%, 12.5%, and 50% with bone marrow, combined and isolated CNS relapses (P = 0.008)., Conclusion: Relapsed ALL remains a challenge, with OS of 19% and 53% among those who underwent HSCT. Abandonment after relapse continues to be prevalent, and we need to integrate social support for providing care and optimal treatment.

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and B-cell ALL (B-ALL) is the most common subtype. The understanding of ALL has advanced significantly in recent years due to genomic sequencing, which has made it possible to identify genetic variants and detect the association between "single nucleotide polymorphisms" (SNP) and certain diseases., Methods: We evaluated 126 patients diagnosed with B-ALL in hospitals in Rio de Janeiro. We described the frequency of polymorphisms in the IKZF1, CDKN2A/2B genes, the contribution of these genetic variants in pediatric ALL, and compared them with the general population of Rio de Janeiro., Results: We demonstrated that the SNPs rs3731217, rs4132601, and rs11978267 were more frequent in patients with B-ALL., Conclusions: These findings contribute to a more complete understanding of B-ALL. They can guide future studies, bringing new perspectives on personalized therapies with reduced side effects and optimization efficacy of B-ALL treatment in children., (© 2024. The Author(s).)

According to the International Agency for Research on Cancer, leukemia ranks 14th in incidence and 11th in mortality and has a 5-year prevalence of approximately 1300,000 cases. Acute lymphoblastic leukemia is the most common hematopoietic syndrome in children during the first 5 years of life and represents approximately 75 % of all neoplasms among the pediatric population. The development of leukemia is strongly governed by DNA alterations that accelerate the growth of bone marrow cells. Currently, the most examined factor in pediatric leukemia is exposure to multiple compounds, such as hydrocarbons. Benzene, an aromatic hydrocarbon, can cause health challenges and is categorized as a carcinogen. Benzene toxicity has been widely associated with occupational exposure. Importantly, studies are underway to generate evidence that can provide clues regarding the risk of environmental benzene exposure and hematological problems in children. In this review, we summarize the existing evidence regarding the effects of benzene on pediatric leukemia, the associations between the effect of benzene on carcinogenesis, and the presence of certain molecular signatures in benzene-associated pediatric leukemia. Although there is sufficient evidence regarding the effects of benzene on carcinogenesis and leukemia, epidemiological research has primarily focused on occupational risk. Moreover, most benzene-induced molecular and cytogenetic alterations have been widely described in adults but not in the pediatric population. Thus, epidemiological efforts are crucial in the pediatric population in terms of epidemiological, clinical, and biomedical research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Prenatal folate supplementation has been consistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Previous germline genetic studies examining the one carbon (folate) metabolism pathway were limited in sample size, scope, and population diversity and led to inconclusive results., Methods: We evaluated whether ∼2,900 single-nucleotide polymorphisms (SNP) within 46 candidate genes involved in the folate metabolism pathway influence the risk of childhood ALL, using genome-wide data from nine case-control studies in the Childhood Cancer and Leukemia International Consortium (n = 9,058 cases including 4,510 children of European ancestry, 3,018 Latinx, and 1,406 Asians, and 92,364 controls). Each study followed a standardized protocol for quality control and imputation of genome-wide data and summary statistics were meta-analyzed for all children combined and by major ancestry group using METAL software., Results: None of the selected SNPs reached statistical significance, overall and for major ancestry groups (using adjusted Bonferroni P-value of 5 × 10-6 and less-stringent P-value of 3.5 × 10-5 accounting for the number of "independent" SNPs). None of the 10 top (nonsignificant) SNPs and corresponding genes overlapped across ancestry groups., Conclusions: This large meta-analysis of original data does not reveal associations between many common genetic variants in the folate metabolism pathway and childhood ALL in various ancestry groups., Impact: Genetic variants in the folate pathway alone do not appear to substantially influence childhood acute lymphoblastic leukemia risk. Other mechanisms such as gene-folate interaction, DNA methylation, or maternal genetic effects may explain the observed associations with self-reported prenatal folate intake., (©2024 The Authors; Published by the American Association for Cancer Research.)

The present study aimed to investigate the real-world results of childhood acute lymphoblastic leukemia (cALL) cases in Fujian, China. The clinical data of 1414 patients with newly diagnosed cALL in Fujian were retrospectively analyzed. Patients were treated according to the Chinese Children Leukemia Group 2008 protocol (CCLG-ALL 2008 group) or Chinese Children's Cancer Group 2015 protocol (CCCG-ALL 2015 group). Cumulative incidence of treatment abandonment (TA) at 5 years was 4.2% ± 0.6% and significantly associated with treatment period and risk stratification. The 5-OS and EFS were significantly higher in the CCCG-ALL 2015 group than in the CCLG-ALL 2008 group. Patients treated with CCCG-ALL 2015 from Fujian Medical Union Hospital had a significantly higher 4-year OS and EFS than did those from the other four hospitals. Real-world TA of cALL greatly decreased, and its long-term survival significantly increased in Fujian, which may be related to optimizing programs, multi-center collaboration, and improving treatment compliance.

Objective: To assess the epidemiological characteristics and prognostic factors of acute leukemia (AL) in children and adolescents, and make comparisons between pediatric and adult patients., Methods: This retrospective cohort study enrolled AL patients from the Surveillance, Epidemiology, and End Results (SEER) 1975-2016. OS in children and adolescents and adults with AL was compared and analyzed separately by age and AL subtype., Results: Totally 61,694 AL patients were identified, with 45,411 (73.6%) adults and 16,283 (26.4%) children and adolescents. From 2000 to 2016, the incidence rates of AL [annual percent changes (APC) = 1.2, 95%CI = 0.9-1.6, P  < 0.05] and acute lymphoblastic leukemia (ALL) (APC = 1.5, 95%CI = 1.1-1.8, P  < 0.05) in children and adolescents were significantly increasing. For adults, AL (APC = 0.9, 95%CI = 0.3-1.5, P  < 0.05), ALL (APC = 2.5, 95%CI = 2.0-3.1, P  < 0.05) and acute myeloid leukemia (AML) (APC = 0.9, 95%CI = 0.4-1.5, P  < 0.05) had significantly elevated incidence rates. Overall survival (OS) in children and adolescents with AL was significantly higher than that in adults with AL (log-rank P  < 0.0001). OS in children and adolescents and adults with ALL, AML and AUL decreased with age (all log-rank P  < 0.0001). Older age, male sex and black race were risk factors for the survival of children and adolescents and adults with ALL, AML and AUL., Conclusion: From 2000 to 2016, the incidence rates of AL in children and adolescents and adults were increasing. Children and adolescents with AL had significantly better OS than adults with AL, and OS declined with age in both children and adolescents and adults with ALL, AML and AUL.

Acute lymphoblastic leukemia (ALL) survivors are at risk for developing subsequent neoplasms, but there is limited information on long-term risks and risk factors for both subsequent malignant neoplasms (SMNs) and subsequent non-malignant neoplasms (SNMNs). We analyzed long-term risk and risk factors for SMNs and SNMNs among 3291 5-year ALL survivors from the Dutch Childhood Cancer Survivor Study-LATER cohort (1963-2014). We calculated standardized incidence ratios (SIRs) and cumulative incidences and used multivariable Cox proportional hazard regression analyses for analyzing risk factors. A total of 97 survivors developed SMNs and 266 SNMNs. The 30-year cumulative incidence was 4.1% (95%CI: 3.5-5.3) for SMNs and 10.4%(95%CI: 8.9-12.1) for SNMNs. Risk of SMNs was elevated compared to the general population (SIR: 2.6, 95%CI: 2.1-3.1). Survivors treated with hematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI) (HR:4.2, 95%CI: 2.3-7.9), and without TBI (HR:4.0,95%CI: 1.2-13.7) showed increased SMN risk versus non-transplanted survivors. Cranial radiotherapy (CRT) was also a risk factor for SMNs (HR:2.1, 95%CI: 1.4-4.0). In conclusion, childhood ALL survivors have an increased SMN risk, especially after HSCT and CRT. A key finding is that even HSCT-treated survivors without TBI treatment showed an increased SMN risk, possibly due to accompanied chemotherapy treatment. This emphasizes the need for careful follow-up of HSCT and/or CRT-treated survivors., (© 2024. The Author(s).)

Using a database of 1974-2003 incident cases of haematological malignancies, we explored the time trend, geographic spread and socio-economic and environmental correlates of ALL incidence in Sardinia, Italy, by sex and age. The age- and sex-standardized (World population) ALL incidence rate was 2.0 per 100,000 (95% CI 1.8 - 2.1) and showed variable trend patterns by sex and age. In the total population, ALL incidence showed an annual per cent change of -1.4% (95% CI -0.59 - -3.34) over the study period, with a knot separating a downward slope in 1974-1996 from an increase in 1996-2003. ALL incidence replicated such pattern in women but not men, whose incidence did not substantially vary over the study period (APC = -2.57%, 95% CI -5.45 - 0.26). Among women, the spatial analysis suggested a clustering of ALL in the southwestern part of the region, whilst only a commune had a high posterior probability of a high ALL incidence among men. Three unrelated communes showed a high posterior probability of ALL at age ≤ 24; only the most populated urban centre showed excess cases at age ≥ 25 years. There was no correlation between the geographic spread of ALL at ages ≤ 24 and ≥ 25 years (p = 0.082). Urban residence was a risk factor for the younger age group. Residences near industrial settlements and in the most populated urban centre were risk factors for subjects aged ≥ 25 years. Our findings suggest age-related differences in ALL aetiology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Leukemia is the fifth most common cancer in Saudi Arabia. The aim of this study was to assess the various patterns of leukemia associated with age, gender, and nationality in this region., Methods: This cross-sectional study was conducted at the regional laboratory in Makkah, Saudi Arabia, from April to November 2023. Descriptive statistics were presented as frequencies and percentages by using the GraphPad Prism software., Results: This study included 107 patients, and the results showed that leukemia cases were higher in males than females and more prevalent in older patients (above 50 years of age). Overall, acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) were the most common types of leukemia among Saudi patients. In addition, AML was the most prevalent type of leukemia in males and females, followed by ALL. Data also revealed that ALL was the most common type in the younger population, whereas AML was highly prevalent in older patients., Conclusions: In conclusion, this study provides valuable information about the patterns of leukemia reported at the regional laboratory in Makkah and will help in designing management and preventive approaches for these patients. This epidemiological investigation is also valuable for establishing proper medical databases.

Background: Accurate estimation of body composition, particularly, Body Cell Mass (BCM), which is independent of hydration status is important in children with cancer. This study aimed to accurately measure the anthropometry and body composition of children with Acute Lymphoblastic Leukaemia (ALL) at diagnosis and compare them with healthy children from South India., Methods: This was a cross-sectional study in children aged 2 to 8 y with ALL from St. John's Medical College Hospital, Bengaluru, and age and sex-matched, normal-weight children recruited as controls from communities. Anthropometry (weight, height, circumferences), skinfolds and body composition measurements using a whole-body potassium counter were performed. Body mass index-for-age, weight and height for age z-scores were calculated using WHO child growth standards. Biochemical markers, dietary intake and physical activity details were recorded. Categorical and continuous variables were analyzed by chi-square and independent t-tests respectively.     Results: The mean age of the children with ALL (n = 39) was 4.6±1.9 y and control group (n=39) was 4.7±1.9 y; 61.5% were boys. The prevalence of underweight, overweight/obesity and stunting were 17.9%, 7.7%, and 10.3% respectively. The mean weight and height, of children with ALL and children in the control group were 16.8±6.2 kg and 16.4±4.1 kg, 104.3±14.9 cm and 105.1±12.2 cm, respectively with no statistical difference. Children with ALL showed lower body cell mass index kg/m2 (4.6± 0.8), compared to children in the control group (4.7±0.9) p=0.527, but higher fat mass index kg/m2 (3.6±1.1 vs. 3.4±0.8) p=0.276., Conclusion: At diagnosis, anthropometric and body composition measurements were similar between children with ALL and children in the control group. The BCM showed a non-significant trend of being lower in children with ALL, which requires close monitoring during treatment. Evaluating early-stage nutritional status and body composition can help in planning appropriate interventions during treatment to prevent long term non-communicable diseases.

Background: Acute Lymphoblastic Leukemia (ALL) is the most prevalent neoplasia in children and teenagers in Mexico. Although epidemiological data supports that children's residence close to emissions from vehicular traffic or industrial processes increases the risk of ALL; and the IARC states that benzene, PAHs, and PM 2.5 are well-known environmental carcinogens, there is a gap in linking these carcinogenic hazards with the sources and their distribution from scenario perspective., Aim: To identify ALL clusters in the population under 19 years of age and characterize the environment at the neighborhood level by integrating information on sources of carcinogenic exposure using spatial analysis techniques in the Metropolitan Area of San Luis Potosi, Mexico., Methods: Using the Kernel Density test, we designed an ecological study to identify ALL clusters from incident cases in the population under 19 years of age. A multicriteria analysis was conducted to characterize the risk at the community level from carcinogenic sources. A hierarchical cluster analysis was performed to characterize risk at the individual level based on carcinogenic source count within 1 km for each ALL case., Results: Eight clusters of carcinogenic sources were located within the five identified ALL clusters. The multicriteria analysis showed high-risk areas (by density of carcinogenic source) within ALL clusters., Conclusions: This study has a limited source and amount of available data on ALL cases, so selection bias is present as well as the inability to rule out residual confounding factors, since covariates were not included. However, in this study, children living in environments with high vehicular density, gas stations, brick kilns, incinerators, commercial establishments burning biomass, or near industrial zones may be at higher risk for ALL., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: High ambient temperature is increasingly common due to climate change and is associated with risk of adverse pregnancy outcomes. Acute lymphoblastic leukaemia is the most common malignancy in children, the incidence is increasing, and in the USA disproportionately affects Latino children. We aimed to investigate the potential association between high ambient temperature in pregnancy and risk of childhood acute lymphoblastic leukaemia., Methods: We used data from California birth records (children born from Jan 1, 1982, to Dec 31, 2015) and California Cancer Registry (those diagnosed with childhood cancer in California from Jan 1, 1988, to Dec 31, 2015) to identify acute lymphoblastic leukaemia cases diagnosed in infants and children aged 14 years and younger and controls matched by sex, race, ethnicity, and date of last menstrual period. Ambient temperatures were estimated on a 1-km grid. The association between ambient temperature and acute lymphoblastic leukaemia was evaluated per gestational week, restricted to May-September, adjusting for confounders. Bayesian meta-regression was applied to identify critical exposure windows. For sensitivity analyses, we evaluated a 90-day pre-pregnancy period (assuming no direct effect before pregnancy), adjusted for relative humidity and particulate matter less than 2·5 microns in aerodynamic diameter, and constructed an alternatively matched dataset for exposure contrast by seasonality., Findings: 6849 cases of childhood acute lymphoblastic leukaemia were identified and, of these, 6258 had sufficient data for study inclusion. We also included 307 579 matched controls. Most of the study population were male (174 693 [55·7%] of the 313 837 included in the study) and of Latino ethnicity (174 906 [55·7%]). The peak association between ambient temperature and risk of acute lymphoblastic leukaemia was observed in gestational week 8, where a 5°C increase was associated with an odds ratio of 1·07 (95% CI 1·04-1·11). A slightly larger effect was seen among Latino children (OR 1·09 [95% CI 1·04-1·14]) than non-Latino White children (OR 1·05 [1·00-1·11]). The sensitivity analyses supported the results of the main analysis., Interpretation: Our findings suggest an association between high ambient temperature in early pregnancy and risk of childhood acute lymphoblastic leukaemia. Further replication and investigation of mechanistic pathways might inform mitigation strategies., Funding: Yale Center on Climate Change and Health, The National Center for Advancing Translational Science, National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: A recent single-center study reported a significant increase in acute myeloid leukaemia (AML) cases, including mixed-phenotype acute leukaemia (MPAL), after exposure to direct acting agents (DAA). We investigated whether DAA use increased the risk of AML in patients with chronic hepatitis C virus (HCV) infection., Methods: We conducted a disproportionality analysis of the WHO Pharmacovigilance database Vigibase up to 2020. Queries focused on all DAAs, subclasses, combinations or each DAA separately as well as interferon and ribavirin as negative controls. The primary outcome was AML. Secondary outcomes were AML without MPAL, MPAL, acute lymphoid leukemia (ALL) and acute leukemia (AL, high-level term encompassing AML, ALL, MPAL and unspecified acute leukemia [UAL]). The information component (IC0.25) and proportional reporting ratio (PRR0.25) were computed to assess a potential pharmacovigilance signal., Results: We identified 49 notifications reporting any AL occurrence after anti-HCV treatments from June 1997 to December 2020: 23 (47%) involved a DAA, 24 (49%) interferon and 12 (24%) ribavirin. The DAAs sofosbuvir and ledipasvir were suspected in 74% (n = 17) and 39% (n = 9) of cases. The events reported were AML (n = 22), ALL (n = 11), AML and ALL (n = 1) and UAL (n = 15) and no MPAL. DAA, interferon or ribavirin were not significantly associated with AML, ALL or AL., Conclusion: This study did not find any association between DAA exposure and the occurrence of AML. Nevertheless, vigilance should remain, particularly for MPAL, which may not have been well captured in our study because of its rareness and high risk of misclassification., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C SCHEIFER, A DECHARTRES and B LEBRUN-VIGNES declare that they have no conflicts of interest. P LEBRAY has served as a speaker or a consultant from ASTELLAS and GILEAD and has received research funding from GILEAD. F Tubach is head of the clinical research unit of Pitié-Salpêtrière and Charles Foix hospitals and the pharmacoepidemiology center of Assistance Publique Hôpitaux de Paris, that have received research funding, grants and fees for consultant activities from a large number of pharmaceutical companies, that have contributed indiscriminately to the salaries of its employees. She is not employed by these structures and didn't receive any personal remuneration from these companies., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Researchers have used commercial databases containing residential addresses to reduce exposure misclassification in case-control studies. Our objective is to evaluate the potential systematic bias regarding case status when reconstructing residential locations from commercial databases., Methods: Our study population of 3640 Colorado-born children includes 520 children diagnosed with acute lymphocytic leukemia between 2002 and 2019. We aligned addresses and date ranges obtained from LexisNexis with registry dates to determine three dichotomous outcomes: Found in LexisNexis, conception date found in LexisNexis, and reference date/diagnosis date found in LexisNexis. We applied logistic regression to determine whether outcomes differed by case status., Results: Mothers of cases were 39% more likely to be found in LexisNexis than mothers of controls (OR = 1.39, 95% CI: 0.97, 2). Of the mothers found in LexisNexis, a conception address was 33% more likely (OR= 1.33, 95% CI: 1.06, 1.66) and a reference/diagnosis address was 60% more likely (OR= 1.60, 95% CI: 1.21, 2.12) to be found for mothers of cases than mothers of controls., Conclusion: This study indicates that use of commercial databases to reconstruct residential locations may systematically bias results in case-control studies of childhood cancers., Competing Interests: Declaration of Competing Interest We have read, approved, and accept responsibility for the manuscript. We declare that we have no potential conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Per- and polyfluoroalkyl substances (PFAS) are widespread and environmentally persistent chemicals with immunotoxic properties. Children are prenatally exposed through maternal transfer of PFAS to cord blood, but no studies have investigated the relationship with childhood leukemia., Methods: We measured maternal serum levels of 19 PFAS in first-trimester samples collected in 1986-2010 and evaluated associations with acute lymphoblastic leukemia in full-term offspring (aged younger than 15 years) for 400 cases and 400 controls in the Finnish Maternity Cohort, matched on sample year, mother's age, gestational age, birth order, and child's sex. We analyzed continuous and categorical exposures, estimating odds ratios (ORs) and 95% confidence intervals (CIs) via conditional logistic regression adjusted for maternal smoking and correlated PFAS (ρ ≥ ±0.3). We also stratified by calendar period, mean diagnosis age, and the child's sex., Results: N-methyl-perfluorooctane sulfonamidoacetic acid was associated with acute lymphoblastic leukemia in continuous models (per each doubling in levels: ORperlog2 = 1.22, 95% CI = 1.07 to 1.39), with a positive exposure-response across categories (OR>90th percentile = 2.52, 95% CI = 1.33 to 4.78; Ptrend = .01). Although we found no relationship with perfluorooctane sulfonic acid overall, an association was observed in samples collected in 1986-1995, when levels were highest (median = 17.9 µg/L; ORperlog2 = 4.01, 95% CI = 1.62 to 9.93). A positive association with perfluorononanoic acid was suggested among first births (Pinteraction = .06). The N-methyl-perfluorooctane sulfonamidoacetic acid association was mainly limited to children diagnosed before age 5 years (Pinteraction = .02). We found no consistent patterns of association with other PFAS or differences by sex., Conclusions: These novel data offer evidence of a relationship between some PFAS and risk of the most common childhood cancer worldwide, including associations with the highest levels of perfluorooctanesulfonic acid and with a precursor, N-methyl-perfluorooctane sulfonamidoacetic acid., (Published by Oxford University Press 2023.)

Background: Acute lymphocytic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) are among the commonest types of childhood cancer. Some previous studies suggested that elevated ultraviolet radiation (UVR) exposures increase ALL risk; many more indicate NHL risk is reduced., Methods: We assessed age<20 ALL/NHL incidence in Surveillance, Epidemiology and End Results data using AVGLO-derived UVR irradiance/cumulative radiant exposure measures, using quasi-likelihood models accounting for underdispersion, adjusted for age, sex, racial/ethnic group and other county-level socioeconomic variables., Results: There were 30,349 cases of ALL and 8062 of NHL, with significant increasing trends of ALL with UVR irradiance (relative risk (RR) = 1.200/mW/cm 2 (95% CI 1.060, 1.359, p = 0.0040)), but significant decreasing trends for NHL (RR = 0.646/mW/cm 2 (95% CI 0.512, 0.816, p = 0.0002)). There was a borderline-significant increasing trend of ALL with UVR cumulative radiant exposure (RR = 1.444/MJ/cm 2 (95% CI 0.949, 2.197, p = 0.0865)), and significant decreasing trends for NHL (RR = 0.284/MJ/cm 2 (95% CI 0.166, 0.485, p < 0.0001)). ALL and NHL trend RR is substantially increased among those aged 0-3. All-age trend RRs are most extreme (increasing for ALL, decreasing for NHL) for Hispanics for both UVR measures., Conclusions: Our more novel finding, of excess UVR-related ALL risk, is consistent with some previous studies, but is not clear-cut, and in need of replication., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: Acute lymphoblastic leukemia (ALL) is a type of blood cancer that affects white blood cells. Here, we use data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, to estimate the burden and incidence rate changes in adolescents and young adults (AYA) ALL in the Western Pacific Region and to reveal potential risk factors of incidence- and mortality rates., Methods: The GBD 2019 study data was stratified by sex, age, country, and territory. We calculated the Estimated annual percentage changes (estimated APC) in mortality and incidence rates for each of the 25 countries and territories of the western Pacific region from 1990 to 2019., Results: This study found global AYA ALL incidence rates had increased while the mortality rates had decreased between 1990 and 2019. Moreover, healthcare access and quality (HAQ), and government per capita health spending were identified as country-level risk factors of AYA ALL incidence rates, while HAQ, male education, and sex were identified as mortality rate predictors in 25 Western Pacific Region countries., Conclusion: To address and reduce the burden of incidence and mortality among AYA, various regions around the world, particularly developing countries, could revise their AYA prevention and treatment strategies., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and among the most common malignancies in young adults and requires a unique pattern of healthcare utilization including an acute/emergent presentation and an intensive initial 8 months of therapy followed by two years of outpatient treatment. The COVID-19 pandemic caused massive global disruptions in healthcare use and delivery. This report aims to examine the effects of the COVID-19 pandemic on the presentation, diagnosis and continued management of childhood and young adult ALL in regard to utilization and cost of care among commercially insured individuals in the United States., Results: Utilizing a commercial insurance claims database, 529 pediatric and young adult patients were identified who were diagnosed with ALL between January 2016 and March 2021. New diagnoses were evaluated by era and demographics. Utilization was measured by COVID-related era as number of inpatient and outpatient encounters, inpatient days, and cumulative cost during the initial 8 months of therapy. None of these cost or utilization factors changed significantly during or shortly after the pandemic. These findings reinforce that the necessary care for pediatric and young adult ALL was unwavering despite the massive shifts in the healthcare system caused by the COVID-19 pandemic. This provides a valuable benchmark as we further examine the factors that influence the pandemic's impact on health equity and access to care, especially in vulnerable pediatric and young adult populations. This is the first investigation of the effect of the COVID-19 pandemic on utilization and cost of care in pediatric and young adult cancer., (© 2024. The Author(s).)

Background: Acute lymphoblastic leukemia (ALL) has survival rates of greater than 90% in developed nations. However, various sociodemographic factors adversely affect outcome rates in low- and middle-income countries (LMICs)., Objective: To study induction outcome of ALL and various factors affecting it., Methods: This was a prospective cohort study which enrolled 86 children up to the age of 18 years with newly diagnosed ALL registered in newly established pediatric hematology and oncology division over the duration of 3 years. Sociodemographic and clinical data was collected. Outcome was assessed using morphological remission, minimal residual disease (MRD) and mortality rate., Results: Of the 170 children with malignancies registered, 86 were ALL. Mean age was 7.09 ± 4.07 years and the M: F ratio of 1.32:1. Sixteen (38.09%) of them had severe acute malnutrition and another 16 (38.09%) had moderate acute malnutrition. Thirty (68.18%) children over 5 years were undernourished. Seventy-four (86.05%) were B-ALL and 12 (13.95%) T-ALL. In total, 28.77% had WBC counts greater than 50 × 10 9 /L. t (12;21) was the most common cytogenetic abnormality. Majority (60.46%) of the patients belonged to lower socioeconomic status. Seventy-one (93.42%) patients completed induction of which 100% attained morphological remission and 64 (90.14%) were MRD negative. There were five mortalities, three (60%) due to sepsis and 2 (40%) due to hemophagocytic lymphohistiocytosis. Fifty (65.78%) children had morbidities during induction, febrile neutropenia being the commonest., Conclusions: Successful induction outcome rates at par with high-income countries can be achieved even in resource-limited settings of LMIC with support from government and NGOs. Decentralized cancer care centers can effectively pave the way in reducing cancer mortality in children of lower socioeconomic status residing in rural areas., (Copyright © 2024 Copyright: © 2024 Indian Journal of Cancer.)

Adolescent and young adults (AYAs) belong to a unique category of patients diagnosed with acute lymphoblastic leukaemia (ALL). Bloodstream infection (BSI) is a leading cause of treatment-related mortality in ALL patients. However, the epidemiology and risk factors for mortality from BSIs in AYA patients remain unclear. In this study, we analysed these aspects in AYAs patients and compared similarities and differences with children (<15 years old) and older adults (>39 years old). We analysed the pathogenic epidemiology, antibiotic resistance and BSI risk factors of 73 children, 180 AYAs, and 110 older adults with ALL in three comprehensive hospitals from January 2010 to August 2021. The data on BSIs in AYAs were compared to that of the other two groups. In this study, the epidemiology of BSIs in AYAs was similar to that of older adult patients. Concerning clinical characteristics, most AYAs and older adults with BSIs were in a relapsed or uncontrolled state (34.5% vs. 35.4%, p = 0.861). In terms of pathogen distribution, Gram-negative bacteria (GNB) were the most common causative pathogens in AYAs and older adult groups. Extended-spectrum beta-lactamase (ESBL)-producing bacteria were more commonly found in AYAs than in children (32.8% vs. 16.4%, p = 0.09). Regarding risk factors, the length of hospitalization (>14 days) and renal inadequacy (creatinine ≥ 177 μmol/L) were influencing factors for 30-day mortality in AYAs patients with BSIs. In our study, AYA patients with BSIs showed clinical characteristics and pathogen distributions similar to those of older adult patients but quite different from those of children., (© 2024 John Wiley & Sons Australia, Ltd.)

Background: Several studies have documented an increased risk of leukemia among children exposed to magnetic fields from high-voltage power lines, with some evidence of dose-response relation. However, findings in some studies have been inconsistent, and data on the effects of different sources of exposure are lacking. In this study, we evaluated the relation of childhood leukemia risk to exposure to magnetic fields from transformer stations., Methods: We conducted a population-based case-control study in a pediatric population of two Northern Italian provinces of Modena and Reggio Emilia. We included 182 registry-identified childhood leukemia cases diagnosed during 1998-2019 and 726 population controls matched on sex, year of birth, and province of residence. We assessed exposure by calculating distance from childhood residence to the nearest transformer station within a geographical information system, computing disease odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, adjusting for potential confounders. We evaluated exposure using two buffers (15 m and 25 m radius) and assessed two case groups: leukemia (all subtypes) and acute lymphoblastic leukemia (ALL)., Results: Residing within 15 m of a transformer station (vs. ≥15 m) was not appreciably associated with risk of leukemia (all subtypes) or ALL. We found similar results using a less stringent exposure buffer (25 m). Among children aged ≥5 years, the adjusted ORs were 1.3 (95% CI 0.1-12.8) for leukemia and 1.3 (95% CI 0.1-12.4) for ALL using the 15 m buffer, while they were 1.7 (95% CI 0.4-7.0) for leukemia and 0.6 (95% CI 0.1-4.8) for ALL using the 25 m buffer., Conclusions: While we found no overall association between residential proximity to transformer stations and childhood leukemia, there was some evidence for elevated risk of childhood leukemia among children aged ≥5 years. Precision was limited by the low numbers of exposed children., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Wise is a consultant for AbbVie Inc, and the Gates Foundation. Her institution also receives NIH funding for studies outside of this work. Finally, Dr. Wise receives in-kind donations for primary data collection in the PRESTO cohort (Swiss Precision Diagnostics and Kindara.com). All other authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Breastfeeding has been suggested to protect against childhood cancers, particularly acute lymphoblastic leukemia (ALL). However, the evidence stems from case-control studies alone., Objective: To investigate whether longer duration of exclusive breastfeeding is associated with decreased risk of childhood ALL and other childhood cancers., Design, Setting, and Participants: This population-based cohort study used administrative data on exclusive breastfeeding duration from the Danish National Child Health Register. All children born in Denmark between January 2005 and December 2018 with available information on duration of exclusive breastfeeding were included. Children were followed up from age 1 year until childhood cancer diagnosis, loss to follow-up or emigration, death, age 15 years, or December 31, 2020. Data were analyzed from March to October 2023., Exposure: Duration of exclusive breastfeeding in infancy., Main Outcomes and Measures: Associations between duration of exclusive breastfeeding and risk of childhood cancer overall and by subtypes were estimated as adjusted hazard ratios (AHRs) with 95% CIs using stratified Cox proportional hazards regression models., Results: A total of 309 473 children were included (51.3% boys). During 1 679 635 person-years of follow-up, 332 children (0.1%) were diagnosed with cancer at ages 1 to 14 years (mean [SD] age at diagnosis, 4.24 [2.67] years; 194 boys [58.4%]). Of these, 124 (37.3%) were diagnosed with hematologic cancers (81 [65.3%] were ALL, 74 [91.4%] of which were B-cell precursor [BCP] ALL), 44 (13.3%) with central nervous system tumors, 80 (24.1%) with solid tumors, and 84 (25.3%) with other and unspecified malignant neoplasms. Compared with exclusive breastfeeding duration of less than 3 months, exclusive breastfeeding for 3 months or longer was associated with a decreased risk of hematologic cancers (AHR, 0.66; 95% CI, 0.46-0.95), which was largely attributable to decreased risk of BCP-ALL (AHR, 0.62; 95% CI, 0.39-0.99), but not with risk of central nervous system tumors (AHR, 0.96; 95% CI, 0.51-1.88) or solid tumors (AHR, 0.87; 95% CI, 0.55-1.41)., Conclusions and Relevance: In this cohort study, longer duration of exclusive breastfeeding was associated with reduced risk of childhood BCP-ALL, corroborating results of previous case-control investigations in this field. To inform future preemptive interventions, continued research should focus on the potential biologic mechanisms underlying the observed association.

Purpose of Review: To examine the epidemiological data on obesity and leukemia; evaluate the effect of obesity on leukemia outcomes in childhood acute lymphoblastic leukemia (ALL) survivors; assess the potential mechanisms through which obesity may increase the risk of leukemia; and provide the effects of obesity management on leukemia. Preventive (diet, physical exercise, obesity pharmacotherapy, bariatric surgery) measures, repurposing drugs, candidate therapeutic agents targeting oncogenic pathways of obesity and insulin resistance in leukemia as well as challenges of the COVID-19 pandemic are also discussed., Recent Findings: Obesity has been implicated in the development of 13 cancers, such as breast, endometrial, colon, renal, esophageal cancers, and multiple myeloma. Leukemia is estimated to account for approximately 2.5% and 3.1% of all new cancer incidence and mortality, respectively, while it represents the most frequent cancer in children younger than 5 years. Current evidence indicates that obesity may have an impact on the risk of leukemia. Increased birthweight may be associated with the development of childhood leukemia. Obesity is also associated with worse outcomes and increased mortality in leukemic patients. However, there are several limitations and challenges in meta-analyses and epidemiological studies. In addition, weight gain may occur in a substantial number of childhood ALL survivors while the majority of studies have documented an increased risk of relapse and mortality among patients with childhood ALL and obesity. The main pathophysiological pathways linking obesity to leukemia include bone marrow adipose tissue; hormones such as insulin and the insulin-like growth factor system as well as sex hormones; pro-inflammatory cytokines, such as IL-6 and TNF-α; adipocytokines, such as adiponectin, leptin, resistin, and visfatin; dyslipidemia and lipid signaling; chronic low-grade inflammation and oxidative stress; and other emerging mechanisms. Obesity represents a risk factor for leukemia, being among the only known risk factors that could be prevented or modified through weight loss, healthy diet, and physical exercise. Pharmacological interventions, repurposing drugs used for cardiometabolic comorbidities, and bariatric surgery may be recommended for leukemia and obesity-related cancer prevention., (© 2023. The Author(s).)

Objective: There are significant disparities in outcomes among Hispanic patients with acute lymphoblastic leukemia (ALL). Recent studies have demonstrated favorable outcomes of pegaspargase-containing ALL regimens (PEG-CAR) in young adults however, outcomes in Hispanic ethnicity continue to be underreported., Methods: We evaluated outcomes of newly diagnosed, adult B-cell ALL Hispanic and non-Hispanic patients consecutively treated with a PEG-CAR or HyperCVAD between January 2011 and November 2022. The primary endpoint was event-free survival (EFS) while secondary endpoints included cumulative incidence of relapse and overall survival (OS)., Results: Among 105 included patients, 48 (45.7%) were treated with a PEG-CAR and 57 (54.3%) with HyperCVAD. Median age was 38 years (range, 18-75 years), 61% were Hispanic, and 35.2% had poor-genetic risk. Hispanic patients demonstrated significantly worse 5-year EFS with a PEG-CAR compared to that seen with HyperCVAD (HR, 2.58; 95% CI, 1.32-5.04; p = .006) whereas non-Hispanic patients had better outcomes with PIR (52.4% vs. 42.0%). Hispanic ethnicity (p = .015) and male sex (p = .019) were independent predictors for poor OS., Conclusions: Hispanic patients with B-cell ALL had worse EFS with a PEG-CAR as compared with HyperCVAD. Future studies will aim to confirm these findings and establish a tailored treatment approach for this high-risk population., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Mexican and Hispanic children in Mexico and the United States, respectively, have the highest incidence and worst outcomes of pre-B acute lymphoblastic leukemia (ALL) compared with other racial/ethnic groups. Terminal deoxynucleotidyl transferase (TdT) is an intranuclear DNA polymerase normally present on immature lymphocytes (TdT-positive) and distinguishes ALL from mature lymphoid malignancies. We performed a multisite retrospective study to determine the incidence of TdT-negative precursor B-cell acute lymphoblastic leukemia (pre-B ALL) among Mexican, Caucasian, and US-born Hispanic children to correlate TdT expression with patient characteristics and known prognostic factors. Fisher exact test was performed for categorical variables and the Wilcoxon rank-sum test was used for continuous variables. TdT-negative pre-B ALL was most frequently identified in patients with National Cancer Institute high-risk disease ( P =0.014). TdT-negative expression was also most frequently associated with hypodiploid pre-B ALL ( P =0.001) and KMT2A gene rearrangement ( P =0.0012). Mexican children had the highest incidence of TdT-negative ALL compared with Caucasians and US Hispanics ( P <0.001), with an increased incidence of poor prognostic features as well. This study demonstrates significant differences in TdT-negative expression, genomic alterations, and leukemic ploidy based on race and ethnicity., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: COVID-19 in pediatric patients with acute lymphoblastic leukemia or lymphoma (ALL/LLy) has not been described in detail and may affect chemotherapy administration and long-term outcomes., Objective: To describe the clinical presentation of COVID-19 and chemotherapy modifications in pediatric patients with ALL/LLy., Design, Setting, and Participants: This is a retrospective case series of patients at St Jude Children's Research Hospital and its affiliate sites with newly diagnosed ALL/LLy who were treated on the Total XVII protocol (NCT03117751) between March 30, 2020, and June 20, 2022. Participants included patients aged 1 to 18 years who were receiving protocol chemotherapy. Acute symptoms and chemotherapy modifications were evaluated for 60 days after the COVID-19 diagnosis, and viral clearance, adverse events, and second SARS-CoV-2 infections were followed up during the 27-month study period., Exposures: SARS-CoV-2; all patients were screened at least weekly and at symptom onset and/or after known exposure to SARS-CoV-2., Main Outcomes and Measures: Description of the spectrum of COVID-19 illness and chemotherapy modifications., Results: Of 308 pediatric patients, 110 (36%) developed COVID-19 at a median age of 8.2 (IQR, 5.3-14.5) years. Sixty-eight patients (62%) were male. Most patients were in the continuation/maintenance phase of chemotherapy (101 [92%]). Severe disease was rare (7 [6%]) but was associated with older age, higher white blood cell counts at ALL/LLy diagnosis, lower absolute lymphocyte counts at COVID-19 diagnosis, abnormal chest imaging findings, and SARS-CoV-2 reinfection. Rare but serious thrombotic events included pulmonary embolism and cerebral venous sinus thrombosis (n = 1 for each). No multisystem inflammatory syndrome in children or death was seen. SARS-CoV-2 reinfection occurred in 11 patients (10%) and was associated with older age and with receiving standard or high-risk vs low-risk ALL/LLy therapy. Chemotherapy interruptions occurred in 96 patients (87%) and were longer for patients with severe disease, SARS-CoV-2 reinfection, and/or a COVID-19 diagnosis during the pre-Omicron variant period vs the post-Omicron period (after December 27, 2021)., Conclusions and Relevance: In this case series of COVID-19 in pediatric patients with ALL/LLy, severe COVID-19 was rare, but chemotherapy administration was affected in most patients. Long-term studies are needed to establish the outcomes of COVID-19 in this population.

Objectives: This study examines associations of functional outcomes (adaptive functioning and academic achievement) with executive functioning (EF), socioeconomic status (SES), and academic support in pediatric acute lymphoblastic leukemia (ALL) survivors., Methods: Fifty survivors of B-lineage ALL treated with chemotherapy-only (42% female, 76% NHW, ages 6-19) were evaluated on performance-based EF and academic achievement, and parent-rated EF and adaptive functioning. Area deprivation and child opportunity (i.e., SES) were extracted using census blocks and tracts. Academic support data were extracted from chart review., Results: Compared to population norms, pediatric ALL survivors demonstrated significantly lower overall adaptive skills and performance in word reading and math calculation (all p ≤ .011). Frequencies of impairment were significantly elevated on all adaptive scales and in math calculation compared to the population (all p ≤ .002). Parent-rated EF significantly predicted overall adaptive skills (p < .001), while performance-based EF significantly predicted word reading and math calculation (all p < .05). Adaptive functioning was not associated with neighborhood-specific variables or academic support. However, academic support predicted word reading (p < .001), while area deprivation and academic support predicted performance-based EF (all p ≤ .02)., Conclusions: Screening of functional outcomes, targeted intervention, and neuropsychological monitoring are necessary to support pediatric ALL survivors' neurocognitive and psychosocial development., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Abstract: Occupational exposure to medical agents and ionizing radiation has been suggested as a possible risk factor for childhood cancer. However, the relationship between such exposure and pediatric malignant neoplasms has not yet been comprehensively studied. This cohort study aimed to investigate the association between parental occupational exposure to hazardous medical agents or ionizing radiation and the risk of childhood cancer in offspring. Data from a large birth cohort in Japan, which included 104 062 fetuses, were analyzed. The primary outcome was the development of leukemia or brain tumors diagnosed by community physicians during the first 3 years after birth. Exposure factors were medical agents, including anticancer agents, ionizing radiation, and anesthetics, handled by mothers during pregnancy or by fathers for 3 months before conception. The incidence of leukemia, but not of brain tumors, was higher in mothers exposed to anticancer drugs. Multivariable regression analysis showed that maternal exposure to anticancer drugs was associated with an increased risk of leukemia in offspring older than 1 year (adjusted relative risk, 7.99 [95% confidence interval, 1.98-32.3]). Detailed information obtained from medical certificates of patients with identified leukemia revealed no infant leukemia but acute lymphoblastic leukemias in the exposed group. Our findings suggest that maternal occupational exposure to anticancer drugs may be a potential risk factor for acute lymphoblastic leukemia in offspring older than 1 year. Effective prevention methods may be necessary to prevent maternal exposure to anticancer drugs and to reduce the risk of childhood malignant neoplasms., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Abstract: Various socioeconomic and biologic factors affect cancer health disparities and differences in health outcomes. To better characterize the socioeconomic vs biologic determinants of acute lymphoblastic leukemia (ALL) outcomes, we conducted a single-institution, retrospective analysis of adult patients with ALL treated at the University of Chicago (UChicago) from 2010 to 2022 and compared our outcomes with the US national data (the Surveillance, Epidemiology, and End Results [SEER] database). Among 221 adult patients with ALL treated at UChicago, BCR::ABL1 was more frequent in patients with higher body mass index (BMI; odds ratio [OR], 7.64; 95% confidence interval [CI], 1.17-49.9) and non-Hispanic Black (NHB) ancestry (59% vs 24% in non-Hispanic White (NHW) and 20% in Hispanic patients; P = .001). In a multivariable analysis, age (hazard ratio [HR], 6.93; 95% CI, 2.27-21.1) and higher BMI at diagnosis (HR, 10.3; 95% CI, 2.56-41.5) were independent predictors of poor overall survival (OS). In contrast, race or income were not predictors of OS in the UChicago cohort. Analysis of the national SEER database (2010-2020) demonstrated worse survival outcomes in Hispanic and NHB patients than in NHW patients among adolescent and young adults (AYAs) but not in older adults (aged >40 years). Both AYA and older adult patients with higher median household income had better OS than those with lower income. Therefore, multidisciplinary medical care coupled with essential supportive care services offered at centers experienced in ALL care may alleviate the socioeconomic disparities in ALL outcomes in the United States., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Tobacco smoke adversely affects the prognosis of adult cancers including myeloid leukemia, but less is known in children., Methods: We evaluated whether pre- and postnatal exposures to tobacco smoke decrease 5-year survival of 1,235 childhood acute lymphoblastic leukemia (ALL) and 188 childhood acute myeloid leukemia (AML) cases derived from a population-based case-control study in California. Cases were diagnosed between 1995 and 2015 (median follow-up time of 13.2 years overall). We obtained data on tobacco smoking (before conception, during pregnancy, after birth), parental education and income, clinical features, and vital status through 2020. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for mortality associated with smoking, adjusting for sociodemographic characteristics and risk group (ALL only)., Results: About 23% of mothers and 39% of fathers reported smoking and 130 children with ALL and 52 with AML died within 5 years. For AML, increased risks of death were observed among children whose fathers smoked before conception compared with nonsmoking fathers [HR = 1.41; 95% confidence interval (CI), 0.95-3.44 and 3.47; 95% CI, 1.37-8.81, respectively for <20 vs. ≥20 cigarettes per day; Ptrend = 0.01]. HR for child's passive smoking was 1.74, 95% CI, 0.81-3.73. Paternal preconception smoking may also reduce 5-year survival among ALL with favorable prognostic molecular subtypes (high hyperdiploidy and absence of IKZF1 gene deletion), although the associations did not reach statistical significance (Pheterogeneity = 0.07)., Conclusions: Paternal preconception smoking decreased 5-year survival of childhood AML., Impact: Knowledge of exposure to tobacco smoking should be integrated in the treatment plan of childhood leukemias., (©2023 American Association for Cancer Research.)

Objective: To evaluate if the comorbidity and coinfections presented by SARS-CoV-2 infection vs. COVID-19 impact our Mexican children., Method: Prospective and observational study that included the 2020-2021 peak influenza season. All patients with a diagnosis of infection by SARS-CoV-2 vs. COVID-19 who were admitted to the Hospital Infantil de Mexico were analyzed. Real-time RT-PCR for SARS-CoV-2 was performed in all patients, determining E, RdRp and RP genes and protein N, as well as RT-PCR for detection of respiratory viruses., Results: The inclusion criteria were met by 163 patients. The group with the highest risk of becoming ill was adolescents (40.4%), followed by schoolchildren and preschoolers (21.4% and 19.6% of the cases, respectively). There were three cases with viral coinfection: two (1.2%) with parvovirus B-19 and one (0.6%) with herpes type I; another two (1.2%) showed bacterial coinfection. The main comorbidity were obesity, acute lymphoblastic leukemia and arterial hypertension. Regarding mortality, we only had four cases (2.4%)., Conclusions: Obesity, cancer, hypertension, heart disease and diabetes are comorbidity present in our patients, as referred to in literature, but not coinfections. In our study, we did not have any associated mortality related to comorbidity., (Copyright: © 2024 Permanyer.)

The most common complications related to the treatment of childhood acute lymphoblastic leukemia (ALL) are infections. The aim of the study was to analyze the incidence and mortality rates among pediatric patients with ALL who were treated in 17 Polish pediatric hematology centers in 2020-2021 during the pandemic. Additionally, we compared these results with those of our previous study, which we conducted in the years 2012-2017. The retrospective analysis included 460 patients aged 1-18 years with newly diagnosed ALL. In our study, 361/460 (78.5%) children were reported to have microbiologically documented bacterial infections during chemotherapy. Ten patients (2.8%) died due to sepsis. Fungal infections were reported in 99 children (21.5%), of whom five (5.1%) died due to the infection. We especially observed an increase in bacterial infections during the pandemic period compared to the previous study. The directions of our actions should be to consider antibiotic prophylaxis, shorten the duration of hospitalization, and educate parents and medical staff about complications (mainly infections) during anticancer therapy. It is necessary to continue clinical studies evaluating infection prophylaxis to improve outcomes in childhood ALL patients., (© 2023. The Author(s).)

Objective: to conduct a comparative analysis of the incidence of malignant oncohematological diseases structure among the population of the 4 most ecologically disadvantaged cities of the Dnipropetrovsk region, taking into account the possible influence of various adverse environmental factors (radiation and chemical pollution of air, water and soil) for the period 2006-2017., Materials and Methods: 1948 cases of acute myeloblastic and lymphoblastic leukemia, chronic myeloid and lymphocytic leukemia in residents of 4 cities of the Dnipropetrovsk region were analyzed, taking into account the possible influence of adverse environmental factors (radiation, air pollution, etc.). We used clinical and hematological data per patient and statistic information on these diseasis incidence in the region., Results: An analysis of the oncohematological patients incidence structure, namely: acute lymphoblastic (C91.0) and myeloblastic leukemia (C92.0), chronic lymphocytic (C91.1) and myeloid (C92.1) leukemia, over 12 years in environmentally disadvantaged cities of Dnipropetrovsk region have been conducted. A comparative analysis of the incidence of these diseases among the population of 4 cities of the Dnipropetrovsk region was carried out, taking into account the possible influence of adverse environmental factors (radiation, air pollution, etc.). An excess of the incidence rates of the above-mentioned oncohematological diseases for the period 2006-2017 was revealed in the cities of Dnipro, Kryvyi Rih, Kamianske and Zhovti Vody, where environmental factors significantly affect the increase in morbidity due to pollution mainly by radioactive and chemical substances., (I. O. Selina, I. S. Dyagil.)

Purpose: To assess the prevalence and severity of and describe dental anomalies in children treated for acute lymphoblastic leukemia (ALL) under recent Dana-Farber Cancer Institute (DFCI) protocols. Methods: Patients aged between 14 and 25 years old having received a diag- nosis of ALL before the age of 11 years and after September 2000 received clinical and radiographic oral examinations. Results: Dental anomalies were observed in 26 (51.0 percent) of 51 subjects. Microdontia was the most prevalent dental defect (39.2 percent). Impacted permanent second molars were observed in five (9.8 percent) patients. Being age five years or younger at diagnosis significantly increased the prevalence and severity of dental anomalies (P<0.001). Conclusions: Recent DFCI protocols showed a decreased prevalence of dental disturbances. The anomalies observed may still alter the development of the dental arches and occlusion in pediatric ALL survivors. Further research is needed to confirm the association between ALL treatment and permanent second molar impaction.

Background: Children with acute lymphoblastic leukaemia (ALL) experience multiple symptoms that occur in complicated patterns and negatively affect patient outcomes. To date, no systematic review has been performed on the prevalence of symptoms in children with ALL., Objective: The study aimed to report and analyse the prevalence of symptoms in children with ALL during treatment., Methods: A systematic search was conducted in eight databases (PubMed, Ovid Embase, Web of Science, CINAHL, PsycINFO, China WanFang Database, China Science and Technology Journal Database, and China National Knowledge Infrastructure) for studies published between January 1, 2000, and August 12, 2023. The methodological quality of the included studies was evaluated and a meta-analysis was performed to pool the prevalence of symptoms., Results: In total, 17 studies were included, from which 34 symptoms were identified. The symptom prevalence ranged between 1.5 and 91.0% and the most frequent symptoms observed were fatigue, lack of energy, dry mouth, lack of appetite, sweating, and feeling irritable, which occurred in at least 60% of the patients., Conclusions: Symptoms remain highly prevalent in paediatric patients with ALL, which provides support for the need for symptom assessment in the clinical setting. Specific intervention is urgently needed to mitigate the symptoms in children with ALL and help them cope with the symptom burden., (© 2023. The Author(s).)

A fully powered randomized controlled cancer trial can be challenging to conduct in children because of difficulties in enrollment of pediatric patients due to low disease incidence. One way to improve the feasibility of trials in pediatric patients, when clinically appropriate, is through borrowing information from comparable external adult trials in the same disease. Bayesian analysis of a pediatric trial provides a way of seamlessly augmenting pediatric trial efficacy data with data from external adult trials. However, not all external adult trial subjects may be equally clinically relevant with respect to the baseline disease severity, prognostic factors, co-morbidities, and prior therapy observed in the pediatric trial of interest. The propensity score matching method provides a way of matching the external adult subjects to the pediatric trial subjects on a set of clinically determined baseline covariates, such as baseline disease severity, prognostic factors and prior therapy. The matching then allows Bayesian information borrowing from only the most clinically relevant external adult subjects. Through a case study in pediatric acute lymphoblastic leukemia (ALL), we examine the utility of propensity score matched mixture and power priors in bringing appropriate external adult efficacy information into pediatric trial efficacy assessment, and present considerations for scaling fixed borrowing from external adult data.

Background: Parent psychological distress during childhood cancer treatment has short- and long-term implications for parent, child, and family well-being. Identifying targetable predictors of parental distress is essential to inform interventions. We investigated the association between household material hardship (HMH), a modifiable poverty-exposure defined as housing, food, or utility insecurity, and severe psychological distress among parents of children aged 1-17 years with acute lymphoblastic leukemia (ALL) enrolled on the multicenter Dana-Farber ALL Consortium Trial 16-001., Methods: This was a secondary analysis of parent-reported data. Parents completed an HMH survey within 32 days of clinical trial enrollment (T0) and again at 6 months into therapy (T1). The primary exposure was HMH at T0 and primary outcome was severe parental distress at T0 and T1, defined as a score greater than or equal to 13 on the Kessler-6 Psychological Distress Scale. Multivariable models were adjusted for ALL risk group and single parent status., Results: Among 375 evaluable parents, one-third (32%; n = 120/375) reported HMH at T0. In multivariable analyses, T0 HMH was associated with over twice the odds of severe psychological distress at T0 and T1 HMH was associated with over 5 times the odds of severe distress at T1., Conclusions: Despite uniform clinical trial treatment of their children at well-resourced pediatric centers, HMH-exposed parents-compared with unexposed parents-experienced statistically significantly increased odds of severe psychological distress at the time of their child's leukemia diagnosis, which worsened 6 months into therapy. These data identify a high-risk parental population who may benefit from early psychosocial and HMH-targeted interventions to mitigate disparities in well-being., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Patient re-engagement with primary care physicians (PCPs) after cancer treatment is essential to facilitate survivorship care and to meet non-oncology primary care needs. We identified rates and predictors of PCP visits both during and after treatment among a population-based cohort of children with acute lymphoblastic leukemia (ALL)., Methods: Children of age less than 18 years at ALL diagnosis in Ontario between 2002 and 2012 were linked to administrative data and matched to controls without cancer. PCPs at diagnosis were identified and PCP visit rates during treatment compared between patients and controls. Post-treatment PCP visit rates were also calculated. Predictors included demographic-, disease-, and PCP-related variables., Results: A total of 743/793 (94%) patients and 3112/3947 (79%) controls had a PCP at diagnosis. Almost half of patients (361/743, 45%) did not visit their PCP during treatment. Visit rate during treatment was 0.64 per person per year (PPPY) versus 1.4 PPPY among controls (adjusted rate ratio [aRR] 0.47, 95th confidence interval [95CI]: 0.40-0.54; p < .0001). No disease- or PCP-related factors were associated with visit rates. Total 711 patients completed frontline therapy; 287 (40.4%) did not have a PCP visit after treatment. Nonetheless, survivors overall visited PCPs post treatment more often than controls (aRR 1.4, 95CI: 1.2-1.6; p < .0001). Survivors who saw their PCP during treatment had post-treatment visit rates twice that of other survivors (aRR 2.0, 95CI: 1.6-2.5; p < .0001)., Conclusions: Only a portion of children with ALL see their PCPs during treatment and return to PCP care following treatment completion. Post-treatment engagement with PCPs may be improved by PCP involvement during ALL treatment., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: Several studies have suggested an excess risk of leukemia among children living close to high-voltage power lines and exposed to magnetic fields. However, not all studies have yielded consistent results, and many studies may have been susceptible to confounding and exposure misclassification., Methods: We conducted a case-control study to investigate the risk of leukemia associated with magnetic field exposure from high-voltage power lines. Eligible participants were children aged 0-15 years residing in the Northern Italian provinces of Modena and Reggio Emilia. We included all 182 registry-identified childhood leukemia cases diagnosed in 1998-2019, and 726 age-, sex- and province-matched population controls. We assessed exposure by calculating distance from house to nearest power line and magnetic field intensity modelling at the subjects' residence. We used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for potential confounders (distance from nearest petrol station and fuel supply within the 1000 m-buffer, traffic-related particulate and benzene concentrations, presence of indoor transformers, percentage of urban area and arable crops)., Results: In multivariable analyses, the OR comparing children living <100 m from high-voltage power-lines with children living ≥400 m from power-lines was 2.0 (95% CI 0.8-5.0). Results did not differ substantially by age at disease diagnosis, disease subtype, or when exposure was based on modeled magnetic field intensity, though estimates were imprecise. Spline regression analysis showed an excess risk for both overall leukemia and acute lymphoblastic leukemia among children with residential distances <100 m from power lines, with a monotonic inverse association below this cutpoint., Conclusions: In this Italian population, close proximity to high-voltage power lines was associated with an excess risk of childhood leukemia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Wise is a consultant for AbbVie Inc, and the Gates Foundation. Her institution also receives NIH funding for studies outside of this work. Finally, Dr. Wise receives in-kind donations for primary data collection in the PRESTO cohort (Swiss Precision Diagnostics and Kindara.com). All other authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Polyethylene glycol (PEG)-asparaginase (pegaspargase) is a key agent in chemotherapy for acute lymphoblastic leukemia (ALL), but recipients frequently experience allergic reactions. We hypothesized that by decreasing antibody-producing CD20-positive B cells, rituximab may reduce these reactions. Children and adolescents (aged 1-18 years) with newly diagnosed B-ALL treated on the St. Jude Total XVII study were randomized to induction therapy with or without rituximab on day 3 (cohort 1) or on days 6 and 24 (cohort 2). Patient clinical demographics, CD20 expression, minimal residual disease (MRD), rituximab reactions, pegaspargase allergy, anti-pegaspargase antibodies, and pancreatitis were evaluated. Thirty-five patients received rituximab and 37 did not. Among the 35 recipients, 16 (45.7%) experienced a grade 2 or higher reaction to rituximab. There were no differences between recipients and non-recipients in the incidence of pegaspargase reactions (P  >  0.999), anti-pegaspargase antibodies (P  =  0.327), or pancreatitis (P  =  0.480). CD20 expression on day 8 was significantly lower in rituximab recipients (P  <  0.001), but there were no differences in MRD levels on day 8, 15, or at the end of induction. Rituximab administration during induction in pediatric patients with B-ALL was associated with a high incidence of infusion reactions with no significant decrease in pegaspargase allergies, anti-pegaspargase antibodies, or MRD., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

IKZF1 (IKAROS family Zinc Finger 1) alteration is an essential regulator of both T- and B-cell lineage specification with leukemogenic potential. IKZF1 deletion have been described in childhood acute lymphoblastic leukemia (ALL) with varying prevalence often influenced by underlying cytogenetics and also shown to have diverse prognostic significance. We aimed to evaluate the prevalence and prognostic significance of IKZF1 deletion among childhood ALL. Electronic databases of MEDLINE, EMBASE and SCOPUS were searched and 32 studies found eligible. Estimated prevalence of IKZF1 deletion among BCR::ABL1 negative and BCR::ABL1 positive ALL patients was 14% (95%CI:13-16%, I 2  = 79%; 26 studies) and 63% (95%CI:59-68% I 2  = 42%; 10 studies) respectively. Most common site of IKZF1 deletion was whole chromosome (exon1-8) deletion in 32.3% (95%CI: 23.8-40.7%) followed by exon 4-7 deletion in 28.6% (95%CI: 19.7-37.5%). A positive minimal residual disease at the end of induction was more common among patients with IKZF1 deletion, odds ratio: 3.09 (95%CI:2.3-4.16, I 2  = 54%; 15 studies). Event-free survival and overall survival were significantly worse for IKZF1 deletion, hazard ratio (HR): 2.10 (95%CI:1.90-2.32, I 2  = 28%; 31 studies) and HR: 2.38 (95%CI:1.93-2.93, I 2  = 40; 15 studies) respectively. In summary, the current meta-analysis highlights the frequency of IKZF1 deletion and its negative impact on survival in childhood ALL. Further studies exploring the influence of IKZF1 deletion in the presence of classical cytogenetic and other copy number alterations would further help in characterising its prognostic role., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)