Interventional probability of causation (IPoC) with epidemiological and partial mechanistic evidence: benzene vs. formaldehyde and acute myeloid leukemia (AML).

INTRODUCTION: Causal epidemiology for regulatory risk analysis seeks to evaluate how removing or reducing exposures would change disease occurrence rates. We define interventional probability of causation (IPoC) as the change in probability of a disease (or other harm) occurring over a lifetime or other specified time interval that would be caused by a specified change in exposure, as predicted by a fully specified causal model. We define the closely related concept of causal assigned share (CAS) as the predicted fraction of disease risk that would be removed or prevented by a specified reduction in exposure, holding other variables fixed. Traditional approaches used to evaluate the preventable risk implications of epidemiological associations, including population attributable fraction (PAF) and the Bradford Hill considerations, cannot reveal whether removing a risk factor would reduce disease incidence. We argue that modern formal causal models coupled with causal artificial intelligence (CAI) and realistically partial and imperfect knowledge of underlying disease mechanisms, show great promise for determining and quantifying IPoC and CAS for exposures and diseases of practical interest. METHODS: We briefly review key CAI concepts and terms and then apply them to define IPoC and CAS. We present steps to quantify IPoC using a fully specified causal Bayesian network (BN) model. Useful bounds for quantitative IPoC and CAS calculations are derived for a two-stage clonal expansion (TSCE) model for carcinogenesis and illustrated by applying them to benzene and formaldehyde based on available epidemiological and partial mechanistic evidence. RESULTS: Causal BN models for benzene and risk of acute myeloid leukemia (AML) incorporating mechanistic, toxicological and epidemiological findings show that prolonged high-intensity exposure to benzene can increase risk of AML (IPoC of up to 7e-5, CAS of up to 54%). By contrast, no causal pathway leading from formaldehyde exposure to increased risk of AML was identified, consistent with much previous mechanistic, toxicological and epidemiological evidence; therefore, the IPoC and CAS for formaldehyde-induced AML are likely to be zero. CONCLUSION: We conclude that the IPoC approach can differentiate between likely and unlikely causal factors and can provide useful upper bounds for IPoC and CAS for some exposures and diseases of practical importance. For causal factors, IPoC can help to estimate the quantitative impacts on health risks of reducing exposures, even in situations where mechanistic evidence is realistically incomplete and individual-level exposure-response parameters are uncertain. This illustrates the strength that can be gained for causal inference by using causal models to generate testable hypotheses and then obtaining toxicological data to test the hypotheses implied by the models-and, where necessary, refine the models. This virtuous cycle provides additional insight into causal determinations that may not be available from weight-of-evidence considerations alone.

Impact of aging on acute myeloid leukemia epidemiology and survival outcomes: A real-world, population-based longitudinal cohort study.

Acute myeloid leukemia (AML) is a severe and fatal form of leukemia that is prevalent in the older population. In this longitudinal retrospective study, we investigated the epidemiology and survival rates of patients diagnosed with de novo acute myeloid leukemia in South Korea from Jan 1, 2011, to Aug 31, 2020. We used real-world data from the Health Insurance Review and Assessment Service database. We observed an increase in the number of acute myeloid leukemia cases, with age-specific incidence rates escalating in older patients. In contrast a long-term decrease from 1.94 to 1.77 per 100,000 individuals was found in the age-standardized incidence rates. Meanwhile, age-standardized prevalence rates ascended from 8.93 to 9.67 per 100,000 individuals, with a remarkable increase in the age-specific prevalence rate for those aged 80 years and above. Survival rates were notably better in younger or treated patients, and in those who underwent Hematopoietic stem cell transplantation. The time of diagnosis did not affect the survival of patients younger than 65 years. However, the most recent survival rates were significantly lower for patients 65 or older, as shown in the unadjusted Cox survival analysis. After adjustments in the analysis, it was found that the overall survival rates of the most recently diagnosed group improved significantly compared with those diagnosed earlier, with a hazard ratio of 0.90 (95% confidence interval, 0.84-0.97). This improvement may potentially be influenced by the enhanced treatment alternatives available for newly diagnosed older patients aged 65 years or older. In conclusion, aging appears to fuel an increase in the number of acute myeloid leukemia cases and mortality. Further studies are warranted to understand the impact of aging on acute myeloid leukemia treatment outcomes and devise efficacious care strategies for older patients.

Epidemiological characteristics and influencing factors of acute leukemia in children and adolescents and adults: a large population-based study.

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.

Myeloid neoplasms post cytotoxic therapy: epidemiology, pathogenesis outcomes, prognostic factors, and treatment options.

Myeloid neoplasms post cytotoxic therapy (MN-pCT) are a category includes AML, MDS, and MDS/MPN arising in patients exposed to cytotoxic (DNA-damaging) therapy for an unrelated condition in 2022 version World Health Organization (WHO) classification. With improved survival of patients with tumors, the incidence of MN-pCT after chemotherapy and/or radiation therapy among patients with tumors has gradually risen. However, the outcome of MN-pCT is poorer than that of primary myeloid neoplasms. This review summarizes the current understanding based on existing research, as a foundation for further research on MN-pCT.

Household income and health-related quality of life in children receiving treatment for acute myeloid leukemia: Potential impact of selection bias in health equity research.

OBJECTIVE: Examine the influence of household income on health-related quality of life (HRQOL) among children with newly diagnosed acute myeloid leukemia (AML). DESIGN: Secondary analysis of data prospectively collected from pediatric patients receiving treatment for AML at 14 hospitals across the United States. EXPOSURE: Household income was self-reported on a demographic survey. The examined mediators included the acuity of presentation and treatment toxicity. OUTCOME: Caregiver proxy reported assessment of patient HRQOL from the Peds QL 4.0 survey. RESULT: Children with AML (n = 131) and caregivers were prospectively enrolled to complete PedsQL assessments. HRQOL scores were better for patients in the lowest versus highest income category (mean ± SD: 76.0 ± 14 household income <$25,000 vs. 59.9 ± 17 income ≥$75,000; adjusted mean difference: 11.2, 95% CI: 2.2-20.2). Seven percent of enrolled patients presented with high acuity (ICU-level care in the first 72 h), and 16% had high toxicity (any ICU-level care); there were no identifiable differences by income, refuting mediating roles in the association between income and HRQOL. Enrolled patients were less likely to be Black/African American (9.9% vs. 22.2%), more likely to be privately insured (50.4% vs. 40.7%), and more likely to have been treated on a clinical trial (26.7% vs. 18.5%) compared to eligible unenrolled patients not enrolled. Evaluations of potential selection bias on the association between income and HRQOL suggested differences in HRQOL may be smaller than observed or even in the opposing direction. CONCLUSIONS: While primary analyses suggested lower household income was associated with superior HRQOL, differential participation may have biased these results. Future studies should partner with patients/families to identify strategies for equitable participation in clinical research.

Targetable genetic abnormalities in patients with acute myeloblastic leukemia across age groups.

Incidence of potential targetable genetic abnormalities by age in AML.

Risk of cancer in relatives of patients with myelodysplastic neoplasia and acute leukemias.

BACKGROUND: The risk of cancer among relatives of patients with either myelodysplastic neoplasia (MDS), acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) has not been thoroughly examined. METHODS: We linked the Danish Civil Registration System with the Danish Cancer Registry, the Danish National Acute Leukemia Registry, and the Danish Myelodysplastic Syndrome Database to estimate the relative risk of cancer among relatives of patients with MDS/AML/ALL. We used standardized incidence ratios (SIRs), i.e., the ratio of observed to expected number of cancers among the relatives as a measure of relative risk. RESULTS: We identified 13010 first-degree (FDR) and 22051 second-degree (SDR) relatives of 8386 patients with MDS/ALL/AML. Disregarding basal cell carcinoma (BCC), the relative risk for cancer overall was increased in both FDR (SIR=1.3; 95% confidence interval (CI) 1.1-1.4) and SDR (SIR=1.5; 95% CI 1.2-1.8). SIRs among FDRs were statistically significantly increased for malignant melanoma, BCC and for the combined groups of cancers of the male genital organs, urinary tract, and MDS/AML/ALL. Among SDRs, SIRs were statistically significantly increased for malignant melanoma, BCC, and cancers in the digestive organs and peritoneum. CONCLUSIONS: We observed an increased risk of cancer among FDR and SDR of patients with MDS/AML/ALL.

Neurocognitive and psychosocial outcomes in survivors of childhood leukemia with Down syndrome.

OBJECTIVE: The primary aim of this study was to assess the feasibility of a developmentally tailored neurocognitive assessment in survivors of childhood acute leukemia with Down syndrome (DS-leukemia). A secondary aim was to compare outcomes in the DS-leukemia group to a historical comparison group of individuals with DS and no history of childhood cancer. METHODS: Survivors of DS-leukemia (n = 43; 56% male, mean [SD] age at diagnosis = 4.3 [4.5] years; age at evaluation = 15 [7.9] years) completed a neurocognitive assessment battery that included direct measures of attention, executive function, and processing speed, and proxy ratings of attention problems and executive dysfunction. Direct assessment outcomes were compared to a historical comparison cohort of individuals with DS and no history of childhood cancer (DS-control; n = 117; 56% male, mean [SD] age at evaluation = 12.7 [3.4] years). RESULTS: Rates of valid task completion ranged from 54% to 95%, suggesting feasibility for most direct assessment measures. Compared to the DS-control group, the DS-leukemia group had significantly lower completion rates on measures of executive function (p = 0.008) and processing speed (p = 0.018) compared to the DS-control group. There were no other significant group differences in completion rates. Compared to the DS-control group, the DS-leukemia group had significantly more accurate performance on two measures of executive function (p = 0.032; p = 0.005). Compared to the DS-control group, the DS-leukemia group had significantly more problems with executive function as identified on proxy ratings (6.5% vs. 32.6%, p = <0.001). CONCLUSION: Children with Down syndrome (DS) are at increased risk for developing acute leukemia compared to the general population but are systematically excluded from neurocognitive outcome studies among leukemia survivors. This study demonstrated the feasibility of evaluating neurocognitive late effects in leukemia survivors with DS using novel measures appropriate for populations with intellectual developmental disorder.

Survival difference between secondary and de novo acute myeloid leukemia by age, antecedent cancer types, and chemotherapy receipt.

BACKGROUND: This study compared the survival of persons with secondary acute myeloid leukemia (sAML) to those with de novo AML (dnAML) by age at AML diagnosis, chemotherapy receipt, and cancer type preceding sAML diagnosis. METHODS: Data from Surveillance, Epidemiology, and End Results 17 Registries were used, which included 47,704 individuals diagnosed with AML between 2001 and 2018. Multivariable Cox proportional hazards regression was used to compare AML-specific survival between sAML and dnAML. Trends in 5-year age-standardized relative survival were examined via the Joinpoint survival model. RESULTS: Overall, individuals with sAML had an 8% higher risk of dying from AML (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.05-1.11) compared to those with dnAML. Disparities widened with younger age at diagnosis, particularly in those who received chemotherapy for AML (HR, 1.14; 95% CI, 1.10-1.19). In persons aged 20-64 years and who received chemotherapy, HRs were greatest for those with antecedent myelodysplastic syndrome (HR, 2.04; 95% CI, 1.83-2.28), ovarian cancer (HR, 1.91; 95% CI, 1.19-3.08), head and neck cancer (HR, 1.55; 95% CI, 1.02-2.36), leukemia (HR, 1.45; 95% CI, 1.12-1.89), and non-Hodgkin lymphoma (HR, 1.42; 95% CI, 1.20-1.69). Among those aged ≥65 years and who received chemotherapy, HRs were highest for those with antecedent cervical cancer (HR, 2.42; 95% CI, 1.15-5.10) and myelodysplastic syndrome (HR, 1.28; 95% CI, 1.19-1.38). The 5-year relative survival improved 0.3% per year for sAML slower than 0.86% per year for dnAML. Consequently, the survival gap widened from 7.2% (95% CI, 5.4%-9.0%) during the period 2001-2003 to 14.3% (95% CI, 12.8%-15.8%) during the period 2012-2014. CONCLUSIONS: Significant survival disparities exist between sAML and dnAML on the basis of age at diagnosis, chemotherapy receipt, and antecedent cancer, which highlights opportunities to improve outcomes among those diagnosed with sAML.

Development of a risk assessment model for cardiac injury in patients newly diagnosed with acute myeloid leukemia based on a multicenter, real-world analysis in China.

BACKGROUND: Studies have revealed that acute myeloid leukemia (AML) patients are prone to combined cardiac injury. We aimed to identify hematological risk factors associated with cardiac injury in newly diagnosed AML patients before chemotherapy and develop a personalized predictive model. METHODS: The population baseline, blood test, electrocardiogram, echocardiograph, and genetic and cytogenetic data were collected from newly diagnosed AML patients. The data were subdivided into training and validation cohorts. The independent risk factors were explored by univariate and multivariate logistic regression analysis respectively, and data dimension reduction and variable selection were performed using the least absolute shrinkage and selection operator (LASSO) regression models. The nomogram was generated and the reliability and generalizability were verified by receiver operating characteristic (ROC) curves, the area under the curve (AUC) and calibration curves in an external validation cohort. RESULTS: Finally, 499 AML patients were included. After univariate logistic regression, LASSO regression and multivariate logistic regression analysis, abnormal NT-proBNP, NPM1 mutation, WBC, and RBC were independent risk factors for cardiac injury in AML patients (all P < 0.05). The nomogram was constructed based on the above four variables with high accuracy. The area under the curve was 0.742, 0.750, and 0.706 in the training, internal validation, and external validation cohort, respectively. The calibration curve indicated that the model has good testing capability. The Kaplan-Meier curve showed that the higher the risk of combined cardiac injury in AML patients, the lower their probability of survival. CONCLUSIONS: This prediction nomogram identifies hematological risk factors associated with cardiac injury in newly diagnosed AML patients and can help hematologists identify the risk and provide precise treatment options.

Real-world data of AML in Japan: results of JALSG clinical observational study-11 (JALSG-CS-11).

This report covers acute myeloid leukemia (AML) results from a multicenter, prospective observational study of AML, myelodysplastic syndromes, and chronic myelomonocytic leukemia in Japan. From August 2011 to January 2016, 3728 AML patients were registered. Among them, 42% were younger than 65, and the male-to-female ratio was 1.57:1. With a median follow-up time of 1807 days (95% confidence interval [CI]: 1732-1844 days), the estimated 5-year overall survival (OS) rate in AML patients (n = 3707) was 31.1% (95% CI: 29.5-32.8%). Trial-enrolled patients had a 1.7-fold higher OS rate than non-enrolled patients (5-year OS, 58.9% [95% CI: 54.5-63.1%] vs 35.5% [33.3-37.8%], p < 0.0001). Women had a higher OS rate than men (5-year OS, 34% [95% CI; 31.4-36.7%] vs 27.7% [25.7-29.7%], p < 0.0001). The OS rate was lower in patients aged 40 and older than those under 40, and even lower in those over 65 (5-year OS for ages < 40, 40-64, 65-74, ≥ 75: 74.5% [95% CI; 69.3-79.0%] vs 47.5% [44.4-50.6%] vs 19.3% [16.8-22.0%] vs 7.3% [5.5-9.4%], respectively). This is the first paper to present large-scale data on survival and clinical characteristics in Japanese AML patients.

Uptake of novel therapies into first-line treatment for acute myeloid leukemia patients: EU4 + UK perspective.

Aim: To explore the incorporation of novel agents in the first-line setting for acute myeloid leukemia patients. Materials & methods: Observational study based on data from a multi-country cross-sectional retrospective web-based survey sent to 518 physicians in Europe between 2020 and 2021. Information from 2040 patients was analyzed. Results: 604 patients (29.6%) received novel agents in both intensive and non-intensive setting. Comorbidities were not a barrier for the use of novel agents. The presence of tumor mutations was observed to be an important element for treatment decision. Conclusion: There is a progressive incorporation of novel agents for newly diagnosed acute myeloid leukemia patients.

What is this article about? We now have new treatments for patients suffering from a type of blood cancer called acute myeloid leukemia (acronym AML). They are available as the first choice of therapy. In this study we explored how these new treatments are included in daily patient care. What were the results? We reviewed the data of 2040 patients in Europe, obtained from an online survey sent to physicians in two waves (between 2020 and 2021). The use of these new AML treatments was more frequent in patients who presented some specific gene alterations (changes in their DNA sequence) and were in worse health due to other diseases and old age. Most of the new treatments were administered together with other milder chemotherapies. What do the results of the study mean? The results of this study help us understand how new AML treatments are being used.

Pre- and Postnatal Exposures to Tobacco Smoking and Survival of Childhood Acute Lymphoblastic and Myeloid Leukemias in California, United States.

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.

Exposure to persistent organic pollutants in newborn dried blood spots and childhood acute myeloid leukemia.

Acute myeloid leukemia (AML) is a rare malignancy representing 15-20% of all leukemia diagnoses among children. Maternal exposure to persistent organic pollutants is suggestive of increased risk for childhood AML based on existing evidence. We aimed to evaluate the relationship between persistent organic pollutants and childhood AML using newborn dried bloodspots (DBS) from the Michigan BioTrust for Health. We obtained data on AML cases diagnosed prior to 15 years of age (n = 130) and controls (n = 130) matched to cases on week of birth from the Michigan Department of Health and Human Services. We quantified levels of dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), and polybrominated diphenyl ether congener 47 (BDE-47) in newborn DBS. We also evaluated other organochlorine pesticides, polychlorinated biphenyls, polybrominated biphenyl congener 153, and polybrominated diphenyl ethers, though these were not further evaluated as >60% of observations were above the limit of detection for these chemicals. To evaluate the association between each chemical and AML, we used multivariable conditional logistic regression. In our multivariable model of HCB adjusted for month of birth, maternal age at delivery, and area poverty, we observed no association with AML (Odds Ratio [OR] per interquartile range increase: 1.17, 95% CI: 0.80, 1.69). For p,p'-DDE, ORs were significantly lower for those exposed to the highest tertile of p,'p-DDE (≥0.29 pg/mL, OR: 0.32, 95% CI: 0.11, 0.95) compared to the first tertile (<0.09 pg/mL). We observed no statistically significant associations between HCB and BDE-47 and AML. We observed a reduced odds of exposure to p,'p-DDE and an increased, though imprecise, odds of exposure to HCB among AML cases compared to controls. Future studies would benefit from a larger sample of AML patients and pooling newborn DBS across multiple states to allow for additional variability in exposures and evaluation of AML subtypes, which may have differing etiology.

Sociodemographic associations with uptake of novel therapies for acute myeloid leukemia.

Inequitable uptake of novel therapies (NT) in non-cancer settings are known for patients with lower socioeconomic status (SES), People of Color (POC), and older adults. NT uptake equity in acute myeloid leukemia (AML) is not well known. We performed a retrospective cohort study (1/2014-8/2022) of the United States nationwide Flatiron HealthTM electronic health record-derived, de-identified database. We estimated sociodemographic associations with AML NT receipt using incidence rate ratios (IRR). Odds ratios (OR) assessed differences in venetoclax (the most common NT) receipt at community sites and between site characteristics and NT adoption. Of 8081 patients (139 sites), 3102 (38%) received a NT. NT use increased annually (IRR 1.14, 95% confidence interval [1.07, 1.22]). NT receipt was similar between Non-Hispanic-Whites and POC (IRR 1.03, [0.91, 1.17]) and as age increased (IRR 1.02 [0.97, 1.07]). At community sites, Non-Hispanic-Whites were less likely to receive venetoclax (OR 0.77 [0.66, 0.91]); older age (OR 1.05 [1.04, 1.05]) and higher area-level SES were associated with venetoclax receipt (OR 1.23 [1.05, 1.43]). Early NT adopting sites had more prescribing physicians (OR 1.25 [1.13, 1.43]) and higher SES strata patients (OR 2.81 [1.08, 7.66]). Inequities in AML NT uptake were seen by SES; for venetoclax, differential uptake reflects its label indication for older adults and those with comorbidities.

Association between Residential Proximity to Viticultural Areas and Childhood Acute Leukemia Risk in Mainland France: GEOCAP Case-Control Study, 2006-2013.

BACKGROUND: Pesticide exposures are suspected of being a risk factor for several childhood cancers, particularly acute leukemia (AL). Most of the evidence is based on self-reported parental domestic use of pesticides, but some studies have also addressed associations with agricultural use of pesticides near the place of residence. OBJECTIVES: The objective of the study was to evaluate the risk of AL in children living close to vines, a crop subject to intensive pesticide use. METHODS: Data were drawn from the national registry-based GEOCAP study. We included all of the AL cases under the age of 15 years diagnosed in 2006-2013 (n=3,711) and 40,196 contemporary controls representative of the childhood population in France. The proximity of the vines (probability of presence within 200, 500, and 1,000m) and the viticulture density (area devoted to vines within 1,000m) were evaluated around the geocoded addresses in a geographic information system combining three national land use maps. Logistic regression models were used to estimate odds ratios (ORs) for all AL and for the lymphoblastic (ALL) and myeloid (AML) subtypes. Heterogeneity between regions was studied by stratified analyses. Sensitivity analyses were carried out to take into account, in particular, geocoding uncertainty, density of other crops and potential demographic and environmental confounders. RESULTS: In all, about 10% of the controls lived within 1km of vines. While no evidence of association between proximity to vines and AL was found, viticulture density was positively associated with ALL [OR=1.05 (1.00-1.09) for a 10% increase in density], with a statistically significant heterogeneity across regions. No association with AML was observed. The results remained stable in all the sensitivity analyses. CONCLUSION: We evidenced a slight increase in the risk of ALL in children living in areas with high viticulture density. This finding supports the hypothesis that environmental exposure to pesticides may be associated with childhood ALL. https://doi.org/10.1289/EHP12634.

Incidence and Bayesian Mapping of Myeloid Hematologic Malignancies in Sardinia, Italy.

BACKGROUND: The epidemiology of myeloid hematologic malignancies in Italy has been poorly investigated. METHODS: We used a validated database of 1974-2003 incident cases of hematologic malignancies among the resident population (all ages) of Sardinia, Italy, to describe the incidence of myeloid malignancies overall (N = 4389 cases) and by subtype. We investigated the time trend of acute myeloid leukemia (N = 1227 cases), chronic myeloid leukemia (N = 613 cases), and myelodysplastic syndrome (N = 1296 cases), and used Bayesian methods to explore their geographic spread, and Poisson regression analysis to estimate their association with environmental and socio-economic factors. RESULTS: The annual standardized (world population) incidence rate (IR) of myeloid malignancies over the study period was 6.5 per 100,000 (95% CI 6.2-6.7). Myelodysplastic syndromes were the most prevalent subgroup (IR = 1.7, 95% CI 1.5-1.8). Incidence of all myeloid malignancies combined increased sharply during the study period with an annual percent change (APC) of 10.06% (95% CI 9.51-10.61), 19.77% for myelodysplastic syndromes (95% CI 19.63-19.91), and 3.18% (95% CI 2.99-3.37) for acute myeloid leukemia. Chronic myeloid leukemia did not show an upward trend. Apart from sporadic excesses in small rural communities and the major urban area, there was no evidence of spatial clustering. The risk of myeloid malignancies increased with increasing prevalence of sheep breeding. CONCLUSIONS: Our results might prompt further research on the local genetic and environmental determinants of myeloid hematologic malignancies.

Early Life Nutrition Factors and Risk of Acute Leukemia in Children: Systematic Review and Meta-Analysis.

Acute leukemia commonly occurs in young children with peak incidence at the age of 2-5 years. However, the etiology is still unclear and many preventable risk factors still deserve to be reviewed. The focus of this systematic review and meta-analysis is to summarize the evidence concerning early life nourishment (breastfeeding, early life diet), neonatal vitamin K administration and the risk of acute leukemia. All epidemiological studies published up to June 2023 and assessing diet-related risk factors for childhood acute leukemia were identified in two electronic databases (PubMed and Web of Science), with no limits on publication year or language. A total of 38 studies (37 case-control studies and 1 study with pooled analysis) were included. The published risk estimates were combined into a meta-analysis using the Generic Inverse Variance method. The current evidence shows that breastfeeding (yes vs. no) has a protective effect against acute lymphoblastic leukemia (odds ratio = 0.85; 95% CI, 0.76-0.94). Evidence related to the role of other studied factors (foods and supplements) is inconclusive. Further research into the potential role of diet in early life and the risk of acute leukemia is needed to develop prevention strategies at population level. Review Registration: PROSPERO registration no. CRD42019128937.