Childhood Leukemia Research Articles

Role of breastfeeding in disease prevention.

Human milk provides the infant with many bioactive factors, including immunomodulating components, antimicrobials and prebiotics, which modulate the infant microbiome and immune system maturation. As a result, breastfeeding can impact infant health from infancy, through adolescence, and into adulthood. From protecting the infant from infections, to reducing the risk of obesity, type 1 diabetes and childhood leukaemia, many positive health outcomes are observed in infants receiving breastmilk. For the mother, breastfeeding protects against postpartum bleeding and depression, increases weight loss, and long-term lowers the risk of type 2 diabetes, breast and ovarian cancer, and cardiovascular diseases. Beyond infants and mothers, the wider society is also impacted because of avoidable costs relating to morbidity and mortality derived from a lack of human milk exposure. In this review, Medline was used to search for relevant articles to discuss the health benefits of breastfeeding and its societal impact before exploring future recommendations to enhance our understanding of the mechanisms behind breastfeeding's positive effects and promote breastfeeding on a global scale.

The Effect Of Stress and Optimism on Resilience for Parents with Children Leukemia at Ulin Hospital Banjarmasin

Kanker Anak adalah penyakit yang mengancam jiwa dan penyebab utama kematian anak di negara berpenghasilan rendah dan menengah. Keluarga yang memiliki anak dengan penyandang kanker dapat memiliki dampak negatif pada kesejahteraan orang tua. Pengobatan leukemia yang panjang mnyebabkan dampak bagi orang tua oleh karena itu dibutuhkan resiliensi, beberapa faktor yang mempengaruhi resiliensi yakni stres dan optimisme. Tujuan penelitian ini adalah mengetahui hubungan stres dan optimisme terhadap resilience ibu yang memiliki anak penyandang leukemia di RSUD Ulin Banjarmasin. Desain survei analitik dan rancangan Cros-Sectional. Sampel adalah Ibu memiliki anak penyandang leukemia berjumlah 30 dengan teknik purposive sampling. Instrumen menggunakan kuesiner Stress Scale (PSS). Optimisme menggunakan kuesioner Life Orientation Test – Revised (LOT-R), Resiliensi menggunakan The Corner Davidson Resilience Questionnaire (CD-RISC) yang telah teruji validitas dan reabilitas. Analisis data univariat dilakukan untuk mengetahui frekuensi dan presentase, dan bivariat dilakukan menggunakan Kalmogorov-Smirnov untuk mengetahui hubungan antar variabel.

Resiliency process in the family after childhood leukaemia diagnosis: A longitudinal qualitative study.

To construct a conceptual framework on the process of family resilience during the first year following childhood leukaemia diagnosis. A longitudinal qualitative interview study. A longitudinal qualitative study following a grounded theory methodology was employed. Semi-structured interviews were conducted with parents of children with leukaemia in a general hospital. The participants were recruited through purposive and theoretical sampling and longitudinal engagement was achieved by conducting interviews at 1, 3, 6, and 12 months after the leukaemia diagnosis. The core category and categories were saturated following the enrolment of parents of children with leukaemia. Data collection and analyses were performed simultaneously. Sixteen parents of children with leukaemia participated. The core category of 'families living with childhood leukaemia' refers to the process of family resilience during the first year following childhood leukaemia diagnosis, which includes three phases: (1) destruction and resiliency period; (2) adjustment and consolidation period; and (3) growth and planning period. This study explored the dynamic, complex and continuous processes of resilience among families coping with childhood leukaemia during the first year following diagnosis. Further research should design tailored family interventions that characterise the different phases of family resilience, aiming to support family well-being, integrity and functioning. Both families and healthcare professionals must create an enabling environment that supports families coping with difficulties. Understanding the different phases of family resilience allows healthcare professionals to provide holistic care that meets the demands of families with childhood leukaemia. Unique knowledge emerged about the family's resiliency process when facing childhood leukaemia, suggesting a family-led revolution in understanding and managing childhood leukaemia. Therefore, the development of phased, resilience-based family interventions is imperative. This study was reported using the COREQ checklist. Patients contributed via study participation.

Particulate Matter Exposure during Pregnancy and Childhood Leukemia Incidence

Leukemia is the most common childhood cancer and its etiology could be related to various environmental contaminants such as particulate matter (PM). The objective of our study is to evaluate the potential association between exposure to PM during pregnancy and the incidence of childhood leukemia. We established a population-based nationwide cohort using the Spanish Birth Registry Statistics database of the National Statistics Institute. We used spatiotemporal land use random forest models to estimate the concentrations of PM10 and PM2.5 for the entire pregnancy and by trimesters. We conducted logistic regression analyses adjusted for various covariates. In addition, we fitted generalized additive models (GAMs) to estimate the non-linear relationship between PM levels and leukemia incidence. The study included 3,112,123 children and 1066 cases of leukemia. The results for the continuous variable of PM10 exposure levels suggested an increased risk of childhood leukemia to be associated with higher exposure. The results for the categorized PM10 variable suggest an increased risk of childhood leukemia among pregnant women whose exposure levels were higher than the median (third and fourth quartiles). The results for PM2.5 were weaker. We found association between exposure to PM10 during pregnancy and an increased risk of childhood leukemia. Our findings indicate that public health interventions should aim to reduce air pollution to lower the incidence of childhood leukemia.

Folate Metabolism and Risk of Childhood Acute Lymphoblastic Leukemia: A Genetic Pathway Analysis from the Childhood Cancer and Leukemia International Consortium.

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. 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. 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. 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. 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.

Early-life tobacco exposure is causally implicated in aberrant RAG-mediated recombination in childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children, yet few environmental risk factors have been identified. We previously found an association between early-life tobacco smoke exposure and frequency of somatic deletions of 8 leukemia driver genes among childhood ALL patients in the California Childhood Leukemia Study. To expand analysis genome-wide and examine potential mechanisms, we conducted tumor whole-genome sequencing in 35 ALL patients, including 18 with high prenatal tobacco exposure and 17 with low exposure as determined by established epigenetic biomarkers. High tobacco exposure patients had significantly more structural variants (P < .001) and deletions (P = .001) genome-wide than low exposure patients. Investigation of off-target RAG recombination revealed that 41% of deletions in the high tobacco exposure patients were putatively RAG-mediated (full RAG motif identified at one or both breakpoints) compared with only 21% in the low exposure group (P = .001). In a multilevel model, deletions in high tobacco exposure patients were 2.44-fold (95% CI:1.13-5.38) more likely to be putatively RAG-mediated than deletions in low exposure patients. No point mutational signatures were associated with prenatal tobacco exposure. Our findings suggest that early-life tobacco smoke exposure may promote leukemogenesis by driving development of somatic deletions in pre-leukemic lymphocytes via off-target RAG recombination.

Transient Differentiation-State Plasticity Occurs during Acute Lymphoblastic Leukemia Initiation.

Leukemia is characterized by oncogenic lesions that result in a block of differentiation, whereas phenotypic plasticity is retained. A better understanding of how these two phenomena arise during leukemogenesis in humans could help inform diagnosis and treatment strategies. Here, we leveraged the well-defined differentiation states during T-cell development to pinpoint the initiation of T-cell acute lymphoblastic leukemia (T-ALL), an aggressive form of childhood leukemia, and study the emergence of phenotypic plasticity. Single-cell whole genome sequencing of leukemic blasts was combined with multiparameter flow cytometry to couple cell identity and clonal lineages. Irrespective of genetic events, leukemia-initiating cells altered their phenotypes by differentiation and dedifferentiation. The construction of the phylogenies of individual leukemias using somatic mutations revealed that phenotypic diversity is reflected by the clonal structure of cancer. The analysis also indicated that the acquired phenotypes are heritable and stable. Together, these results demonstrate a transient period of plasticity during leukemia initiation, where phenotypic switches seem unidirectional. Significance: A method merging multicolor flow cytometry with single-cell whole genome sequencing to couple cell identity with clonal lineages uncovers differentiation-state plasticity in leukemia, reconciling blocked differentiation with phenotypic plasticity in cancer.

Utilization of supportive care medications and opportunities for pre-emptive pharmacogenomic testing in pediatric and young adults with leukemia

This study aimed to evaluate the utilization of drugs with pharmacogenomic guidelines (PGx-drugs) for personalized dosing in pediatric leukemia. A retrospective observational study of pediatric leukemia patients admitted between 2009–2019 at a single-center academic children’s hospital was conducted to determine PGx-drug exposure within 3 years of diagnosis. Along with baseline demographic and clinical characteristics of these patients, data regarding dates of diagnosis, relapse, death were collected. During the study period, inclusion criteria were met by 714 patients. The most frequently given medications were ondansetron (96.1%), morphine (92.2%), and allopurinol (85.3%) during the study period. In this cohort, 82% of patients received five or more PGx-drugs. Patients diagnosed with acute myeloid leukemia and leukemia unspecified were prescribed more PGx-drugs than other types of leukemia. There was a significant relationship between age at diagnosis and the number of PGx-drugs prescribed. Adolescents and adults both received a median of 10 PGx-drugs, children received a median of 6 PGx-drugs, and infants received a median of 7 PGx-drugs (p < 0.001). Patients with recurrent leukemia had significantly more PGx-drugs prescribed compared to those without recurrent disease, 10 drugs and 6 drugs, respectively (p < 0.001). Patients diagnosed with childhood leukemia are high utilizers of PGx-drugs. There is a vital need to understand how PGx testing may be utilized to optimize treatment and enhance quality of life. Preemptive PGx testing is a tool that aids in optimization of drug therapy and decreases the need for later treatment modifications. This can result in financial savings from decreased health-care encounters.

Targeting IGF2BP1 alleviated benzene hematotoxicity by reprogramming BCAA metabolism and fatty acid oxidation

Benzene is the main environmental pollutant and risk factor of childhood leukemia and chronic benzene poisoning. Benzene exposure leads to hematopoietic stem and progenitor cell (HSPC) dysfunction and abnormal blood cell counts. However, the key regulatory targets and mechanisms of benzene hematotoxicity are unclear. In this study, we constructed a benzene-induced hematopoietic damage mouse model to explore the underlying mechanisms. We identified that Insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) was significantly reduced in benzene-exposed mice. Moreover, targeting IGF2BP1 effectively mitigated damages to hematopoietic function and hematopoietic molecule expression caused by benzene in mice. On the mechanics, by metabolomics and transcriptomics, we discovered that branched-chain amino acid (BCAA) metabolism and fatty acid oxidation were key metabolic pathways, and Branched-chain amino acid transaminase 1 (BCAT1) and Carnitine palmitoyltransferase 1a (CPT1A) were critical metabolic enzymes involved in IGF2BP1-mediated hematopoietic injury process. The expression of the above molecules in the benzene exposure population was also examined and consistent with animal experiments. In conclusion, targeting IGF2BP1 alleviated hematopoietic injury caused by benzene exposure, possibly due to the reprogramming of BCAA metabolism and fatty acid oxidation via BCAT1 and CPT1A metabolic enzymes. IGF2BP1 is a potential regulatory and therapeutic target for benzene hematotoxicity.

Flow Cytometry-Based Detection of Minimal/Measurable Residual Disease Predicts Survival Outcomes in Pediatrics, Adolescents, and Young Adults With T-acute Lymphoblastic Leukemia.

Measurable/minimal residual disease (MRD) is considered the single most powerful high-risk factor in acute leukemia, including T-cell acute lymphoblastic leukemia (T-ALL). In this study, we evaluated the impact of flow cytometry (FC)-based detection of MRD on survival outcomes in pediatrics, adolescents, and young adults (AYA) with T-ALL. We included 139 patients, 88 pediatric patients between the ages of one and 14 years, and 51 AYA patients between 15 and 39 years of age, over a period of three years and were treated with the Indian Collaborative Childhood Leukemia Group (ICiCLe) protocol. MRD assessment was performed on post-induction (PI) bone marrow aspirate samples using a 10-color 11-antibody MRD panel on a Gallios instrument (Beckman Coulter, Miami, FL, USA). MRD value > 0.01% was considered positive. PI-MRD status was available in 131 patients. The five-year event-free survival (5-year EFS) in PI-MRD positive patients was inferior to those of negative patients (13.56% vs 79.06%), which was statistically significant (P < 0.001). However, the five-year overall survival (5-year OS) did not show any statistically significant difference between PI-MRD positive and negative T-ALL patients (92.93% vs 94.28%). The hazard ratio (HR) for 5-year EFS and MRD positivity was 8.03 (p-value < 0.0001). HR for 5-year EFS and early T-cell precursor ALL (ETP-ALL) was 2.63 (p = -0.02). PI-MRD detected using FC is a strong predictive factor of inferior survival outcomes in pediatrics, AYA patients with T-ALL. PI-MRD positivity can be used to modify the treatment of T-ALL patients, especially in resource-constrained developing countries where molecular tests are not widely available.

Identification of Risk Factors for Relapse in Childhood Leukemia Using Penalized Semi-parametric Mixture Cure Competing Risks Model.

Leukemia is the most common childhood malignancy. Identifying prognostic factors of patient survival and relapse using more reliable statistical models instead of traditional variable selection methods such as stepwise regression is of great importance. The present study aimed to apply a penalized semi-parametric mixture cure model to identify the prognostic factors affecting short-term and long-term survival of childhood leukemia in the presence of competing risks. The outcome of interest in this study was time to relapse. Study Design: A retrospective cohort study. A total of 178 patients (0‒15 years old) with leukemia participated in this study (September 1997 to September 2016, followed up to June 2021) at Golestan University of Medical Sciences, Iran. Demographic, clinical, and laboratory data were collected, and then a penalized semi-parametric mixture cure competing risk model with smoothly clipped absolute deviation (SCAD) and least absolute shrinkage and selection operator (LASSO) regularizations was used to analyze the data. Important prognostic factors of relapse patients selected by the SCAD regularization method were platelets (150000‒400000 vs.>400000; odds ratio=0.31) in the cure part and type of leukemia (ALL vs. AML, hazard ratio (HR)=0.08), mediastinal tumor (yes vs. no, HR=16.28), splenomegaly (yes vs. no; HR=2.94), in the latency part. In addition, significant prognostic factors of death identified by the SCAD regularization method included white blood cells (<4000 vs.>11000, HR=0.25) and rheumatoid arthritis signs (yes vs. no, HR=5.75) in the latency part. Several laboratory factors and clinical side effects were associated with relapse and death, which can be beneficial in treating the disease and predicting relapse and death time.

Accelerated aging among survivors of childhood leukemia and lymphoma: Estimates of early onset and excess morbidity from the COMPASS model.

10028 Background: Cohort studies have detected an increased risk of accelerated aging among survivors of childhood cancer but the timing and magnitude are not known. Methods: To predict the clinical course of diseases of aging— cancer and cardiovascular disease — among survivors of childhood leukemia and lymphoma compared to the general population, we developed the Cancer Outcomes Microsimulation: Pediatric and Adolescent SurvivorShip (COMPASS) model. The model simulates 8 severe, disabling or life-threatening chronic health conditions (CHCs), including 4 subsequent cancers (breast, colorectal, glial tumors, sarcomas) and 4 cardiovascular diseases (heart failure, myocardial infarction/coronary artery disease, valvular disease, stroke), and excess mortality risks among survivors diagnosed between 1970 and 1999 over the course of their lifetimes. Treatment-related risks varied by patient characteristics (sex, age at diagnosis, diagnosis) and treatment exposures (chemotherapy, radiation dose) and were based on data from the Childhood Cancer Survivor Study (CCSS). Age-related risks and competing mortality were based on national databases (SEER, NHLBI, CDC Wonder). We used model calibration to identify parameter sets that generated outcomes consistent with observed data. Model outcomes included cumulative CHC risk. For comparisons to the general population, age-, sex, and diagnosis year-matched individuals who faced only age-related risks were simulated. Results: Among survivors representative of CCSS participants, the model estimated that 45% of leukemia and 65% of lymphoma survivors will develop at least 1 of the 8 CHCs by age 65. Compared to the estimated 20% cumulative risk for the general population, this represented a two- to three-fold excess morbidity risk among survivors. The age at which 20% of survivors developed at least 1 CHC was 51 years for leukemia and 42 years for lymphoma, suggesting an early onset of 14 and 21 years compared to the general population. Outcomes varied by diagnosis and treatment era due to competing risk changes. Among leukemia survivors diagnosed in the 1990s vs. 1970s, cumulative late recurrence mortality by age 40 (11% to 1%) declined. This combined with a reduction in radiation exposure (79% to 24%) resulted in a greater proportion living into adulthood and developing CHCs by age 65 (38% to 48%). In contrast, among lymphoma survivors, the proportion projected to develop a CHC by age 65 remained stable during the same period (62% to 65%) as late recurrence mortality risk declined (8% to 1%), but almost half still received radiation (90% to 49%). Conclusions: Despite improvements in therapy, leukemia and lymphoma survivors are projected to experience CHC early onset and excess morbidity, underscoring the importance of prevention-focused survivorship care and continued efforts to develop more targeted therapies.

Differential impact of asparaginase discontinuation on outcomes of children with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma.

Asparaginase is essential for treating T-cell acute lymphoblastic leukemia (T-ALL). Despite the ongoing debate on whether T-ALL and T-cell lymphoblastic lymphoma (T-LBL) are the same disease entity or two distinct diseases, patients with T-LBL often receive the same or similar treatment protocols as those with T-ALL. The outcomes of patients with or without L-asparaginase discontinuation were retrospectively analyzed among four national protocols: Japan Association of Childhood Leukemia Study (JACLS) ALL-02 and ALL-97 for T-ALL and Japanese Pediatric Leukemia/Lymphoma Study Group ALB-NHL03 and JACLS NHL-98 for T-LBL. The hazard ratio (HR) was calculated with the Cox regression model by considering L-asparaginase discontinuation as a time-dependent variable. In total, 199 patients with T-ALL, and 133 patients with T-LBL were included. L-asparaginase discontinuation compromised event-free survival (EFS) of T-ALL patients (ALL-02: HR 3.32, 95% confidence interval [CI] 1.40-7.90; ALL-97: HR 3.39, 95%CI 1.19-9.67). Conversely, EFS compromise was not detected among T-LBL patients (ALB-NHL03: HR 1.39, 95%CI 0.41-4.68; NHL-98: HR 0.92, 95%CI 0.11-7.60). The effects of L-asparaginase discontinuation differed between T-ALL and T-LBL. We assume that the differential impact results from (1) the inherent differential response to L-asparaginase between them and/or (2) a less stringent assessment of early treatment response in T-LBL than in T-ALL. Given the poor salvage rate of refractory or relapsed T-ALL and T-LBL, optimization of the frontline therapy is critical, and the current study provides a new suggestion for further treatment modifications. However, larger studies in contemporary intensified treatment protocols are required.

Examining the relationship between land use and childhood leukemia and lymphoma in Tehran

We conducted a hospital-based case–control study to explore the association between proximity to various land use types and childhood leukemia and lymphoma. This research involved 428 cases of childhood leukemia and lymphoma (2016–2021), along with a control group of 428 children aged 1–15 in Tehran. We analyzed the risk of childhood cancer associated with land use by employing logistic regression adjusted for confounding factors such as parental smoking and family history. The odds ratio (OR) for children with leukemia and lymphoma residing within 100 m of the nearest highway was 1.87 (95% CI = 1.00–3.49) and 1.71 (95% CI = 1.00–2.93), respectively, in comparison to those living at a distance of 1000 m or more from a highway. The OR for leukemia with exposure to petrol stations within 100 m was 2.15 (95% CI = 1.00–4.63), and for lymphoma it was 1.09 (95% CI = 0.47–2.50). A significant association was observed near power lines (OR = 3.05; 95% CI = 0.97–9.55) within < 100 m for leukemia. However, no significant association was observed between power lines and the incidence of childhood lymphoma. There was no association between bus stations, major road class 2, and the incidence of childhood leukemia and lymphoma. In conclusion, our results suggest a possible association between the incidence of childhood leukemia and proximity to different urban land uses (i.e., highways and petrol stations). This study is the first step in understanding how urban land use affects childhood leukemia and lymphoma in Tehran. However, comprehensive studies considering individual-level data and specific pollutants are essential for a more nuanced understanding of these associations.

Caracterización clínica y genética de leucemias pediátricas en Montería-Córdoba.

Introduction: leukemias are characterized by the infiltration of malignant cells from the hematopoietic system to the bone marrow and other tissues. 95% of childhood leukemias are acute, of which 75% are lymphoid and 25% myeloid. Although the survival rate can reach up to 90% in high-income countries, for middle- and low-income countries it can vary from 20 to 40%, depending on social and clinical factors that are determinant for survival in the pediatric age. Objective: to describe the clinical and genetic characteristics of a retrospective cohort of pediatric patients with leukemia, in a high complexity clinic in Montería-Córdoba. Methodology: Retrospective cohort study of 124 subjects aged 1-18 years. Frequencies were calculated and associated factors were identified using Ji-square in SPSS 27.0. Results: the highest proportion of patients were men (54.8%), aged 1-5 years (38.7%); 83.1% with lymphoblastic leukemia and 14.5% myeloblastic, the majority with affiliation to the subsidized regime. The clinical and genetic characteristics were not associated with sociodemographic variables. Conclusion: The main leukemias were type B ALL, a higher probability of splenomegaly was found in ALL and more advanced risk levels in AML, determining information to optimize care actions for this pathology

Sociodemographic and Lifestyle Characteristics Associated with Maternal Dietary Patterns in Mexico.

There is scarce evidence on sociodemographic and lifestyle characteristics that may explain adherence to different dietary patterns (DPs) during pregnancy. Our aims were to identify dietary patterns in a sample of pregnant Mexican women and to describe their association with selected sociodemographic and lifestyle characteristics. This is a secondary cross-sectional analysis of 252 mothers of children that participated as controls in a hospital-based case-control study of childhood leukemia. We obtained parents' information about selected sociodemographic characteristics, as well as alcohol and tobacco consumption. We also obtained dietary information during pregnancy. We identified DPs using cluster and factor analyses and we estimated their association with characteristics of interest. We identified two DPs using cluster analysis, which we called "Prudent" and "Non healthy", as well as three DPs through factor analysis, namely "Prudent", "Processed foods and fish", and "Chicken and vegetables". Characteristics associated with greater adherence to "Prudent" patterns were maternal education, older paternal age, not smoking, and being a government employee and/or uncovered population. Likewise, the "Processed foods and fish" pattern was associated with greater maternal and paternal education, as well as those with less household overcrowding. We did not identify sociodemographic variables related to the "Chicken and Vegetables" pattern. Our results may be useful to identify target populations that may benefit from interventions aimed to improve individual dietary decisions during pregnancy.

Trends in childhood leukemia incidence in urban countries and their relation to environmental factors, including space weather.

Leukemia is the most common cancer in children. Its incidence has been increasing worldwide since 1910th, suggesting the presence of common sources of the disease, most likely related to people's lifestyle and environment. Understanding the relationship between childhood leukemia and environmental conditions is critical to preventing the disease. This discussion article examines established potentially-carcinogenic environmental factors, such as vehicle emissions and fires, alongside space weather-related parameters like cosmic rays and the geomagnetic field. To discern the primary contributor, we analyze trends and annual variations in leukemia incidence among 0-14-year-olds in the United States, Canada, Australia, and Russia from 1990 to 2018. Comparisons are drawn with the number of vehicles (representing gasoline emissions) and fire-affected land areas (indicative of fire-related pollutants), with novel data for Russia introduced for the first time. While childhood leukemia incidence is rising in all countries under study, the rate of increase in Russia is twice that of other nations, possibly due to a delayed surge in the country's vehicle fleet compared to others. This trend in Russia may offer insights into past leukemia levels in the USA, Canada, and Australia. Our findings highlight vehicular emissions as the most substantial environmental hazard for children among the factors examined. We also advocate for the consideration of potential modulation of carcinogenic effects arising from variations in cosmic ray intensity, as well as the protective role of the geomagnetic field. To support the idea, we provide examples of potential space weather effects at both local and global scales. The additional analysis includes statistical data from 49 countries and underscores the significance of the magnetic field dip in the South Atlantic Anomaly in contributing to a peak in childhood leukemia incidence in Peru, Ecuador and Chile. We emphasize the importance of collectively assessing all potentially carcinogenic factors for the successful future predictions of childhood leukemia risk in each country.

Prognostic value of indicators of the level of buccal micronuclei in childhood leukemia

Prognostic value of indicators of the level of buccal micronuclei in childhood leukemia

Exercise and QUality Diet after Leukemia: A Randomized Weight Loss Trial among Adult Survivors of Childhood Leukemia in the Childhood Cancer Survivor Study.

Obesity is prevalent in childhood cancer survivors and interacts with cancer treatments to potentiate risk for cardiovascular (CV) death. We tested a remote weight-loss intervention trial that was effective among adults with CV risk factors in a cohort of adult survivors of childhood acute lymphoblastic leukemia (ALL) with overweight/obesity. In this phase III efficacy trial, survivors of ALL enrolled in the Childhood Cancer Survivor Study with a body mass index ≥25 kg/m2 were randomized to a remotely delivered weight-loss intervention versus self-directed weight loss, stratified by history of cranial radiotherapy. The primary endpoint was the difference in weight loss at 24 months in an intent-to-treat analysis. Analyses were performed using linear mixed-effects models. Among 358 survivors (59% female; median attained age: 37 years; IQR: 33-43 years), the baseline mean (SD) weight was 98.6 kg (24.0) for the intervention group (n = 181) and 94.9 kg (20.3) for controls (n = 177). Adherence to the intervention was poor; 15% of individuals in the intervention group completed 24/30 planned coaching calls. Weight at 24 months was available for 274 (77%) participants. After controlling for cranial radiotherapy, sex, race/ethnicity, and age, the mean (SE) change in weight from baseline to 24 months was -0.4 kg (0.8) for the intervention group and 0.2 kg (0.6) for control participants (P = 0.59). A remote weight-loss intervention that was successful among adults with CV conditions did not result in significant weight loss among adult survivors of childhood ALL. Future interventions in this population must be tailored to the unique needs of survivors to encourage engagement and adherence. See related In the Spotlight, p. 1147.

Late Adverse Effects after Treatment for Childhood Acute Leukemia.

The aim of this review is to raise awareness and knowledge among healthcare professionals and policymakers about late adverse effects in survivors of childhood leukemia. With contemporary treatment, over 90% of children with acute lymphoblastic leukemia (ALL) and over 60% with acute myeloid leukemia (AML) are cured. Large cohort studies demonstrate that 20% of ALL and most AML survivors have at least one chronic health condition by 20-25 years after diagnosis. These are life-changing or threatening in some survivors and contribute to increased premature mortality. We describe the frequency, causes, clinical features, and natural history of the most frequent and severe late adverse effects in childhood leukemia survivors, including subsequent malignant neoplasms, metabolic toxicity, gonadotoxicity and impaired fertility, endocrinopathy and growth disturbances, bone toxicity, central and peripheral neurotoxicity, cardiotoxicity, psychosocial late effects, accelerated ageing and late mortality. The wide range of late effects in survivors of haemopoietic stem cell transplant is highlighted. Recent developments informing the approach to long-term survivorship care are discussed, including electronic personalized patient-specific treatment summaries and care plans such as the Survivor Passport (SurPass), surveillance guidelines and models of care. The importance of ongoing vigilance is stressed given the increasing use of novel targeted drugs with limited experience of long-term outcomes. CONCLUSION: It is vital to raise awareness of the existence and severity of late effects of childhood leukemia therapy among parents, patients, health professionals, and policymakers. Structured long-term surveillance recommendations are necessary to standardize follow-up care.