A U.S. Lead Exposure Hotspots Analysis.

To identify U.S. lead exposure risk hotspots, we expanded upon geospatial statistical methods from a published Michigan case study. The evaluation of identified hotspots using five lead indices, based on housing age and sociodemographic data, showed moderate-to-substantial agreement with state-identified higher-risk locations from nine public health department reports (45-78%) and with hotspots of children's blood lead data from Michigan and Ohio (e.g., Cohen's kappa scores of 0.49-0.63). Applying geospatial cluster analysis and 80th-100th percentile methods to the lead indices, the number of U.S. census tracts ranged from ∼8% (intersection of indices) to ∼41% (combination of indices). Analyses of the number of children <6 years old living in those census tracts revealed the states (e.g., Illinois, Michigan, New Jersey, New York, Ohio, Pennsylvania, Massachusetts, California, Texas) and counties with highest potential lead exposure risk. Results support use of available lead indices as surrogates to identify locations in the absence of consistent, complete blood lead level (BLL) data across the United States. Ground-truthing with local knowledge, additional BLL data, and environmental data is needed to improve identification and analysis of lead exposure and BLL hotspots for interventions. While the science evolves, these screening results can inform "deeper dive" analyses for targeting lead actions.

Lead Data Mapping to Prioritize US Locations for Whole-of-Government Exposure Prevention Efforts: State of the Science, Federal Collaborations, and Remaining Challenges.

For this state-of-science overview of geospatial approaches for identifying US communities with high lead-exposure risk, we compiled and summarized public data and national maps of lead indices and models, environmental lead indicators, and children's blood lead surveillance data. Currently available indices and models are primarily constructed from housing-age and sociodemographic data; differing methods, variables, data, weighting schemes, and geographic scales yield maps with different exposure risk profiles. Environmental lead indicators are available (e.g., air, drinking water, dust, soil) at different spatial scales, but key gaps remain. Blood lead level data have limitations as testing, reporting, and completeness vary across states. Mapping tools and approaches developed by federal agencies and other groups for different purposes present an opportunity for greater collaboration. Maps, data visualization tools, and analyses that synthesize available geospatial efforts can be evaluated and improved with local knowledge and blood lead data to refine identification of high-risk locations for prioritizing prevention efforts and targeting risk-reduction strategies. Remaining challenges are discussed along with a work-in-progress systematic approach for cross-agency data integration, toward advancing "whole-of-government" public health protection from lead exposures. (Am J Public Health. 2022;112(S7):S658-S669. https://doi.org/10.2105/AJPH.2022.307051).

Behavioral Health Screening in Military Cystic Fibrosis Centers: A Survey.

INTRODUCTION: Cystic fibrosis (CF) is the most common life-threatening genetic illness in the United States. People with CF as well as their caregivers are up to three times more likely to report experiencing symptoms of depression and anxiety than those without CF. In 2016, the Cystic Fibrosis Foundation and the European Cystic Fibrosis Society came together to form the International Committee on Mental Health in CF and released guidelines outlining behavioral health (BH) screening recommendations for patients with CF and at least one primary caregiver. This study sought to characterize the role of BH care in routine CF treatment within the DoD health care system and identify potential opportunities for improvement. The resultant brief report is intended to elucidate and present identified areas of improvement as well as to inform further research projects in this field. MATERIALS AND METHODS: A representative sample of program leaders (8 of 12; five program directors and three nurse coordinators) from all six affiliate CF centers in the DoD completed a 23-item web-based survey. This study sought to identify the following: (1) What tools are DoD affiliate CF centers using to screen patients with CF and their caregiver(s) for psychological distress and how often does screening take place? (2) What is the composition of the DoD's CF BH teams by specialty and to what degree are BH personnel available to support the needs of CF patients? (3) How comfortable are program directors and nurse coordinators in screening patients with CF and their caregiver(s) for indicators of psychological distress? (4) How familiar are CF BH teams with the use of the U.S. Military's Behavioral Health Data Portal (BHDP)? This descriptive study was approved by the Human Use Committee at the Tripler Army Medical Center. RESULTS: The results of this study indicated that 80% of the DoD affiliate CF centers are screening patients with CF who are 12 years and older and at least one caregiver at least annually for depression and anxiety with the Patient Health Questionnaire depression module and generalized anxiety disorder screening tool, respectively. Reported screening tools for suicidality were not standardized across centers. All respondents indicated that there is a designated social worker in their CF clinic team. Three-quarters of respondents reported that their social worker is physically present in CF clinics 75%-100% of the time. Other types of BH team members varied by clinic. Program directors and nurse coordinators on average indicated feeling "somewhat comfortable" in screening patients with CF for depression, anxiety, and suicidality. Eighty percent of program directors reported being "not so comfortable" in screening caregivers for depression, anxiety, and suicidality, with nurse coordinators on average reporting feeling "somewhat comfortable." Eighty percent of affiliate CF centers indicated that they are unaware of, are not utilizing, or do not have access to the BHDP to screen and record BH data for patients with CF or their caregiver(s). CONCLUSIONS: This study characterized routine CF BH care at DoD affiliate CF centers. Areas for improvement include the standardized use of screening tools for suicidality, increased provider comfort with screening, and streamlined recording and tracking of this data using the BHDP. Limitations of this study include inherent self-report bias, specifically social desirability bias. Steps toward suggested improvements and further utilization of the BHDP may improve BH care for patients with CF and their caregiver(s) in addition to facilitating future research.

Using Small Area Prevalence Survey Methods to Conduct Blood Lead Assessments among Children.

INTRODUCTION: Prevalence surveys conducted in geographically small areas such as towns, zip codes, neighborhoods or census tracts are a valuable tool for estimating the extent to which environmental risks contribute to children's blood lead levels (BLLs). Population-based, cross-sectional small area prevalence surveys assessing BLLs can be used to establish a baseline lead exposure prevalence for a specific geographic region. MATERIALS AND METHODS: The required statistical methods, biological and environmental sampling, supportive data, and fieldwork considerations necessary for public health organizations to rapidly conduct child blood lead prevalence surveys at low cost using small area, cluster sampling methodology are described. RESULTS: Comprehensive small area prevalence surveys include partner identification, background data collection, review of the assessment area, resource availability determinations, sample size calculations, obtaining the consent of survey participants, survey administration, blood lead analysis, environmental sampling, educational outreach, follow-up and referral, data entry/analysis, and report production. DISCUSSION: Survey results can be used to estimate the geographic distribution of elevated BLLs and to investigate inequitable lead exposures and risk factors of interest. CONCLUSIONS: Public health officials who wish to assess child and household-level blood lead data can quickly apply the data collection methodologies using this standardized protocol here to target resources and obtain assistance with these complex procedures. The standardized methods allow for comparisons across geographic areas and over time.

Successes and challenges of implementing a cancer care delivery intervention in community oncology practices: lessons learned from SWOG S1415CD.

BACKGROUND: Cancer Care Delivery (CCD) research studies often require practice-level interventions that pose challenges in the clinical trial setting. The SWOG Cancer Research Network (SWOG) conducted S1415CD, one of the first pragmatic cluster-randomized CCD trials to be implemented through the National Cancer Institute (NCI) Community Oncology Program (NCORP), to compare outcomes of primary prophylactic colony stimulating factor (PP-CSF) use for an intervention of automated PP-CSF standing orders to usual care. The introduction of new methods for study implementation created challenges and opportunities for learning that can inform the design and approach of future CCD interventions. METHODS: The order entry system intervention was administered at the site level; sites were affiliated NCORP practices that shared the same chemotherapy order system. 32 sites without existing guideline-based PP-CSF standing orders were randomized to the intervention (n = 24) or to usual care (n = 8). Sites assigned to the intervention participated in tailored training, phone calls and onboarding activities administered by research team staff and were provided with additional funding and external IT support to help them make protocol required changes to their order entry systems. RESULTS: The average length of time for intervention sites to complete reconfiguration of their order sets following randomization was 7.2 months. 14 of 24 of intervention sites met their individual patient recruitment target of 99 patients enrolled per site. CONCLUSIONS: In this paper we share seven recommendations based on lessons learned from implementation of the S1415CD intervention at NCORP community oncology practices representing diverse geographies and patient populations across the U. S. It is our hope these recommendations can be used to guide future implementation of CCD interventions in both research and community settings. TRIAL REGISTRATION: NCT02728596 , registered April 5, 2016.

Blood Lead Levels in U.S. Children Ages 1-11 Years, 1976-2016.

BACKGROUND: Lead can adversely affect child health across a wide range of exposure levels. We describe the distribution of blood lead levels (BLLs) in U.S. children ages 1-11 y by selected sociodemographic and housing characteristics over a 40-y period. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) II (1976-1980), NHANES III (Phase 1: 1988-1991 and Phase II: 1991-1994), and Continuous NHANES (1999-2016) were used to describe the distribution of BLLs (in micrograms per deciliter; 1µg/dL=0.0483µmol/L) in U.S. children ages 1-11 y from 1976 to 2016. For all children with valid BLLs (n=27,122), geometric mean (GM) BLLs [95% confidence intervals (CI)] and estimated prevalence ≥5µg/dL (95% CI) were calculated overall and by selected characteristics, stratified by age group (1-5 y and 6-11 y). RESULTS: The GM BLL in U.S. children ages 1-5 y declined from 15.2µg/dL (95% CI: 14.3, 16.1) in 1976-1980 to 0.83µg/dL (95% CI: 0.78, 0.88) in 2011-2016, representing a 94.5% decrease over time. For children ages 6-11 y, GM BLL declined from 12.7µg/dL (95% CI: 11.9, 13.4) in 1976-1980 to 0.60µg/dL (95% CI: 0.58, 0.63) in 2011-2016, representing a 95.3% decrease over time. Even so, for the most recent period (2011-2016), estimates indicate that approximately 385,775 children ages 1-11 y had BLLs greater than or equal to the CDC blood lead reference value of 5µg/dL. Higher GM BLLs were associated with non-Hispanic Black race/ethnicity, lower family income-to-poverty-ratio, and older housing age. DISCUSSION: Overall, BLLs in U.S. children ages 1-11 y have decreased substantially over the past 40 y. Despite these notable declines in population exposures to lead over time, higher GM BLLs are consistently associated with risk factors such as race/ethnicity, poverty, and housing age that can be used to target blood lead screening efforts. https://doi.org/10.1289/EHP7932.

Decreases in Young Children Who Received Blood Lead Level Testing During COVID-19 - 34 Jurisdictions, January-May 2020.

Exposure to lead, a toxic metal, can result in severe effects in children, including decreased ability to learn, permanent neurologic damage, organ failure, and death. CDC and other health care organizations recommend routine blood lead level (BLL) testing among children as part of well-child examinations to facilitate prompt identification of elevated BLL, eliminate source exposure, and provide medical and other services (1). To describe BLL testing trends among young children during the coronavirus disease 2019 (COVID-19) pandemic, CDC analyzed data reported from 34 state and local health departments about BLL testing among children aged <6 years conducted during January-May 2019 and January-May 2020. Compared with testing in 2019, testing during January-May 2020 decreased by 34%, with 480,172 fewer children tested. An estimated 9,603 children with elevated BLL were missed because of decreased BLL testing. Despite geographic variability, all health departments reported fewer children tested for BLL after the national COVID-19 emergency declaration (March-May 2020). In addition, health departments reported difficulty conducting medical follow-up and environmental investigations for children with elevated BLLs because of staffing shortages and constraints on home visits associated with the pandemic. Providers and public health agencies need to take action to ensure that children who missed their scheduled blood lead screening test, or who required follow-up on an earlier high BLL, be tested as soon as possible and receive appropriate care.

Blood Lead Levels in U.S. Women of Childbearing Age, 1976-2016.

BACKGROUND: Lead can adversely affect maternal and child health across a wide range of exposures; developing fetuses and breastfeeding infants may be particularly vulnerable. We describe the distribution of blood lead levels (BLLs) in U.S. women of childbearing age and associations with sociodemographic, reproductive, smoking, and housing characteristics over a 40-y period. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) II, NHANES III Phase I and Phase II, and 1999-2016 continuous NHANES were used to describe the distribution of BLLs (given in micrograms per deciliter; 1µg/dL=0.0483µmol/L) in U.S. women 15-49 years of age between 1976 and 2016. For all women with valid BLLs (n=22,408), geometric mean (GM) BLLs and estimated prevalence of BLLs ≥5µg/dL were calculated overall and by selected demographic characteristics. For NHANES II, estimated prevalence of BLLs ≥10 and ≥20µg/dL were also calculated. RESULTS: The most recent GM BLLs (2007-2010 and 2011-2016, respectively) were 0.81µg/dL [95% confidence interval (CI): 0.79, 0.84] and 0.61µg/dL (95% CI: 0.59, 0.64). In comparison, GM BLLs in earlier periods (1976-1980, 1988-1991, and 1991-1994) were 10.37µg/dL (95% CI: 9.95, 10.79), 1.85µg/dL (95% CI: 1.75, 1.94), and 1.53µg/dL (95% CI: 1.45, 1.60), respectively. In 2011-2016, 0.7% of women of childbearing age had BLLs ≥5µg/dL, and higher BLLs were associated with older age, other race/ethnicity, birthplace outside the United States, four or more live births, exposure to secondhand tobacco smoke, and ever pregnant or not currently pregnant. DISCUSSION: Lead exposure in U.S. women of childbearing age is generally low and has substantially decreased over this 40-y period. However, based on these estimates, there are still at least 500,000 U.S. women being exposed to lead at levels that may harm developing fetuses or breastfeeding infants. Identifying high-risk women who are or intend to become pregnant remains an important public health issue. https://doi.org/10.1289/EHP5925.

Integrating Childhood and Adult Blood Lead Surveillance to Improve Identification and Intervention Efforts.

The Centers for Disease Control and Prevention (CDC) collects information on blood lead levels (BLLs) in the United States through the Childhood Blood Lead Surveillance (CBLS) system (<16 years of age) and the Adult Blood Lead Epidemiology and Surveillance (ABLES) program (≥16 years of age). While both of these state-based national programs share the mutual goal of monitoring and reducing lead exposure in the US population, blood lead data for children and adults are maintained in separate data collection systems. This limits the ability to fully describe lead exposure in the US population across these 2 distinct population groups from sources such as take-home and maternal-child lead exposure. In addition, at the state level, having a unified system to collect, maintain, and analyze child and adult blood lead data provides a more efficient use of limited resources. Based on feedback from state partners, CDC is working to integrate CBLS and ABLES data collection systems at the national level. Several states have developed or are developing an integrated child and adult blood lead data collection system. We highlight efforts undertaken in Wisconsin, Minnesota, North Carolina, Iowa, and Oregon to investigate workplace and take-home lead exposure. Integrating blood lead surveillance data at the national level will enhance CDC's ability to monitor sources of lead exposure from both the home and work environments including paint, water, soil, dust, consumer products, and lead-related industries. Together, an integrated child and adult blood lead surveillance system will offer a coordinated, comprehensive, and systematic public health approach to the surveillance and monitoring of reported BLLs across the US population.

The Epidemiology of Benign Prostatic Hyperplasia Associated with Lower Urinary Tract Symptoms: Prevalence and Incident Rates.

This article assesses the reported prevalence and incidence rates for benign prostatic hyperplasia and lower urinary tract symptoms (BPH/LUTS) by age, symptom severity, and race/ethnicity. BPH/LUTS prevalence and incidence rates increase with increasing age and vary by symptom severity. The BPH/LUTS relationship is complex due to several factors. This contributes to the range of reported estimates and difficulties in drawing epidemiologic comparisons. Cultural, psychosocial, economic, and/or disease awareness and diagnosis factors may influence medical care access, symptom reporting and help-seeking behaviors among men with BPH/LUTS. However, these factors and their epidemiologic association with BPH/LUTS have not been thoroughly investigated.

Erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) combined responders to tadalafil after 12 weeks of treatment.

OBJECTIVE: To analyse the proportion of men taking tadalafil 5 mg once daily who experience a combined improvement in symptoms of both erectile dysfunction (ED) and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). MATERIALS AND METHODS: The data from men aged ≥45 years randomized to tadalafil 5 mg once daily or placebo enrolled in one of four randomized, placebo-controlled LUTS/BPH clinical trials were analysed (N = 927). A novel classification of 'combined responders' to ED and LUTS/BPH treatment was defined, based on published criteria for men who showed improvement in both International Index of Erectile Function - Erectile Function domain (IIEF-EF) score and total International Prostate Symptom Score (IPSS). Descriptive analyses assessed the covariate distribution by responder status. Unadjusted and adjusted logistic regressions provided odds ratios with 95% confidence intervals comparing combined responders with all others (partial and non-responders). RESULTS: Among men randomized to tadalafil 5 mg, 40.5% were combined responders (n = 189). Among placebo randomized men, 18.3% were combined responders (n = 84). Combined responders, in the total population, had the highest baseline IPSS and lowest baseline IIEF-EF scores, corresponding to the highest level of dysfunction. The majority of men were aged ≤65 years, white, non-obese, non-smokers, and regular alcohol consumers. Only treatment, baseline IPSS, baseline IIEF-EF, obesity and psychoactive medication use were significantly associated with responder status (P ≤ 0.05). Tadalafil-treated men had 2.8 times significantly increased adjusted odds of being combined responders vs non-responders (P < 0.001). For each unit decrease in baseline IIEF-EF or alcoholic drink consumption per week there was a 4% significant increase in the adjusted odds of being a combined responder to tadalafil therapy. CONCLUSIONS: This novel measure of combined response is useful in differentiating patients with clinically relevant symptom improvement for both ED and LUTS/BPH after treatment with tadalafil 5 mg once daily vs placebo. This combined responder measure may be useful in future assessment of treatment benefits across patient groups after various types of treatment intervention (e.g. surgical vs pharmacotherapy vs non-pharmacological intervention).

The Co-occurring Syndrome-Coexisting Erectile Dysfunction and Benign Prostatic Hyperplasia and Their Clinical Correlates in Aging Men: Results From the National Health and Nutrition Examination Survey.

OBJECTIVE: To establish a descriptive profile of men with coexistent erectile dysfunction (ED) and/or benign prostatic hyperplasia (BPH), ED only or BPH only compared to those with neither condition and to identify the determinants of coexisting disease. MATERIALS AND METHODS: Self-report and/or medication use measures defining ED and BPH were assessed in men aged ≥40 years (N = 2142) between 2001 and 2004 using the National Health and Nutrition Examination Surveys. Descriptive analyses examined the ED and/or BPH covariate distribution. Logistic regressions calculated odds ratios (ORs, 95% confidence interval) comparing men with ED and/or BPH, BPH only, or ED only to men with neither condition. RESULTS: Of 393 men with BPH, 57.8% had coexistent ED, confirming the moderately strong co-occurrence of the conditions (P <.0001). Coexisting ED and/or BPH occurred in 10.6% of participants, whereas 24.4% and 7.7% reported ED and BPH. After age 60, the odds of reporting ED, BPH, or ED/BPH vs neither almost tripled per decade of increasing age, corresponding to prevalence increases. The unadjusted odds of ED and/or BPH vs no disease increased 1.3 times per prostate-specific antigen unit (ng/mL) increase and 1.1 times per C-reactive protein unit (mg/dL) increase. Other predisposing factors for ED and/or BPH included higher body mass index (OR = 2.5), increased antidiabetic (OR = 2.9) or proton pump inhibitor use (OR = 2.3), increased healthcare visits (≥4; OR = 3.5), and more frequent urinary voiding difficulties (OR = 9.7). CONCLUSION: Co-occurring ED and/or BPH is evident in ~10% of men ≥40 years old and is associated with significant clinical correlates. Clinicians need to pay greater attention to this clinically important syndrome in aging men.

General, but not abdominal, overweight increases odds of asthma among Norwegian adolescents: the Young-HUNT study.

AIM: The aim of this analysis was to examine the association between asthma and general and abdominal weight status, defined by age- and sex-specific cut-offs for body mass index (BMI) and waist circumference (WC) in adolescents. METHODS: Participants aged 12-19 years in the Young-HUNT (YH) Study (YH1 1995-1997: n = 8222; YH3 2006-2008: n = 7403) completed self-administered questionnaires in school as part of a series of cross-sectional, population-based studies conducted in Nord-Trøndelag, Norway. Weight, height and WC were measured. Adjusted odds ratios (ORs) and 95% Confidence Intervals (CI) for asthma, defined by self-reported physician diagnosis, were calculated. Potential effect modifiers evaluated included sex and pubertal development status (PDS). RESULTS: Asthma was reported by 11.8% of the adolescents in YH1 and 17.0% in YH3. Asthma odds significantly increased for adolescents with general (OR = 1.33; 95%CI: 1.13, 1.56), but not abdominal, overweight and increased for adolescents with general (OR = 1.34; 95%CI: 1.02, 1.75) or abdominal obesity (OR = 1.36; 95%CI: 1.16, 1.60). Underweight had no association with asthma regardless of weight assessment type, and PDS did not meaningfully influence the associations between asthma and weight. CONCLUSION: Overweight and obesity both increased the odds of asthma in 12-19 year-old Norwegians. WC did not add further information to that already provided by BMI to improve our understanding of the association between asthma and weight.

Childhood body mass index and subsequent physician-diagnosed asthma: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Childhood asthma and obesity prevalence have increased in recent years suggesting a potential association. However, the direction of any association is poorly understood and the potential causal-relationship is unknown. METHODS: We examined the association between overweight/obesity, defined by body mass index (BMI) <18 years of age, and subsequent physician-diagnosed incident asthma at least one year after BMI assessment. We sought to explore potential effect modification by sex. PubMed and Embase were searched using keywords and restricted to subjects aged 0-18 years. There were no date or language restrictions. From each study we extracted: authors, publication date, location, overweight/obesity definitions, asthma definitions, number of participants, recruitment duration, description of cohort, follow-up time, adjusted effect estimates (with 95% CI) and estimates of subgroup analysis. RESULTS: Six prospective cohort studies which focused on children <18 years of age met criteria for inclusion. The combined risk ratio (RR) of overweight was associated with asthma (RR = 1.35; 95% CI = 1.15, 1.58). In boys, the combined RR of overweight on asthma was significant (RR = 1.41; 95% CI = 1.05, 1.88). For girls, when BMI was defined by Z-score, the combined RR of overweight on asthma was also significant (RR = 1.19; 95% CI = 1.06, 1.34). The combined risk ratio (RR) of obesity was associated with asthma in both boys and girls (RR = 1.50; 95% CI = 1.22, 1.83), in boys only (RR = 1.40; 95% CI = 1.01, 1.93) and in girls only (RR = 1.53; 95% CI = 1.09, 2.14). CONCLUSIONS: Overweight and, especially, obese children are at increased risk of subsequent physician diagnosed asthma in comparison to normal weight children. Except for sex, no studies reported any other potential effect modifiers. The observed sex effects were inconsistent.

Whole-exome sequencing of a pedigree segregating asthma.

BACKGROUND: Despite the success of genome-wide association studies for asthma, few, if any, definitively causal variants have been identified and there is still a substantial portion of the heritability of the disease yet to be discovered. Some of this "missing heritability" may be accounted for by family-specific coding variants found to be segregating with asthma. METHODS: To identify family-specific variants segregating with asthma, we recruited one family from a previous study of asthma as reporting multiple asthmatic and non-asthmatic children. We performed whole-exome sequencing on all four children and both parents and identified coding variants segregating with asthma that were not found in other variant databases. RESULTS: Ten novel variants were identified that were found in the two affected offspring and affected mother, but absent in the unaffected father and two unaffected offspring. Of these ten, variants in three genes (PDE4DIP, CBLB, and KALRN) were deemed of particular interest based on their functional prediction scores and previously reported function or asthma association. We did not identify any common risk variants segregating with asthma, however, we did observe an increase in the number of novel, nonsynonymous variants in asthma candidate genes in the asthmatic children compared to the non-asthmatic children. CONCLUSIONS: This is the first report applying exome sequencing to identify asthma susceptibility variants. Despite having sequenced only one family segregating asthma, we have identified several potentially functional variants in interesting asthma candidate genes. This will provide the basis for future work in which more families will be sequenced to identify variants across families that cluster within genes.

Mitochondrial DNA in residual leukemia cells in cerebrospinal fluid in children with acute lymphoblastic leukemia.

UNLABELLED: This feasibility study was designed to assess the ability to measure mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) cells that contributed to minimal disease/persistent or residual disease (MD/PRD) from children with acute lymphoblastic leukemia (ALL). Increase in mtDNA copies in cancer cells has been suggested to play a role in MD/PRD. CSF as well as blood specimens from 6 children were assayed for MD/PRD and mtDNA copy numbers by quantitative real-time polymerase chain reaction. Of 7 MD/PRD-positive specimens, 6 had increased mtDNA copy numbers; while 11 MD/PRD-negative specimens had no increase in mtDNA copy numbers, p < 0.003. This is the first proof-of-concept study to measure mtDNA copy numbers in MD/PRD-positive CSF specimens from children with ALL. Increase of mtDNA copy numbers in MD/PRD childhood ALL cells and its significance as a mechanism for recurrence requires further investigation. KEYWORDS: Minimal residual disease; Acute lymphoblastic leukemia; Central nervous system; Cerebrospinal fluid; Mitochondria.