Odds Of Acute Lymphoblastic Leukemia Research Articles

Infant feeding practices and childhood acute leukemia: Findings from the Childhood Cancer & Leukemia International Consortium.

Increasing evidence suggests that breastfeeding may protect from childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). However, most studies have limited their analyses to any breastfeeding, and only a few data have examined exclusive breastfeeding, or other exposures such as formula milk. We performed pooled analyses and individual participant data metaanalyses of data from 16 studies (N=17 189 controls; N=10 782 ALL and N=1690 AML cases) from the Childhood Leukemia International Consortium (CLIC) to characterize the associations of breastfeeding duration with ALL and AML, as well as exclusive breastfeeding duration and age at introduction to formula with ALL. In unconditional multivariable logistic regression analyses of pooled data, we observed decreased odds of ALL among children breastfed 4 to 6months (0.88, 95% CI 0.81-0.96) or 7 to 12 months (OR 0.85, 0.79-0.92). We observed a similar inverse association between breastfeeding ≥4months and AML (0.82, 95% CI 0.71-0.95). Odds of ALL were reduced among children exclusively breastfed 4 to 6months (OR 0.73, 95% CI 0.63-0.85) or 7 to 12 months (OR 0.70, 95% CI 0.53-0.92). Random effects metaanalyses produced similar estimates, and findings were unchanged in sensitivity analyses adjusted for race/ethnicity or mode of delivery, restricted to children diagnosed ≥1year of age or diagnosed with B-ALL. Our pooled analyses indicate that longer breastfeeding is associated with decreased odds of ALL and AML. Few risk factors for ALL and AML have been described, therefore our findings highlight the need to promote breastfeeding for leukemia prevention.

Infections and the development of childhood acute lymphoblastic leukemia: a population-based study

An infectious trigger for childhood acute lymphoblastic leukemia is hypothesized and we assessed the association between the rate, type, and critical exposure period for infections and the development of acute lymphoblastic leukemia. We conducted a matched case-control study using administrative databases to evaluate the association between the rate of infections and childhood acute lymphoblastic leukemia diagnosed between the ages of 2-14 years from Ontario, Canada and we used a validated approach to measure infections. In 1600 cases of acute lymphoblastic leukemia, and 16 000 matched cancer-free controls aged 2-14 years, having >2 infections/year increased the odds of childhood acute lymphoblastic leukemia by 43% (odds ratio = 1.43, 95% confidence interval 1.13-1.81) compared to children with ≤0.25 infections/year. Having >2 respiratory infections/year increased odds of acute lymphoblastic leukemia by 28% (odds ratio =1.28, 95% confidence interval 1.05-1.57) compared to children with ≤0.25 respiratory infections/year. Having an invasive infection increased the odds of acute lymphoblastic leukemia by 72% (odds ratio =1.72, 95% confidence interval 1.31-2.26). Having an infection between the age of 1-1.5 years increased the odds of acute lymphoblastic leukemia by 20% (odds ratio = 1.20, 95% confidence interval 1.04-1.39). Having more infections increased the odds of developing childhood acute lymphoblastic leukemia and having an infection between the ages of 1-1.5 years increased the odds of childhood acute lymphoblastic leukemia.

Early immune stimulation and childhood acute lymphoblastic leukemia in Costa Rica: A comparison of statistical approaches

BackgroundAlthough epidemiologic studies suggest that early immune stimulation is protective against childhood leukemia, evidence for this relationship is equivocal for Hispanic children, who are disproportionately affected by this disease. The complex biological processes underlying immune stimulation and leukemogenesis may benefit from novel statistical approaches that account for mixed exposures and their nonlinear interactions. In this study, we utilized targeted machine learning and traditional statistical methods to investigate the association of multiple measures of early immune stimulation with acute lymphoblastic leukemia (ALL) in Costa Rican children. Materials and methodsWe used data from a population-based case-control study conducted in Costa Rica (2001–2003). Cases of ALL (n = 240) were diagnosed in 1995–2000 (age >1 year and <15 years at diagnosis) and were identified through the National Cancer Registry and National Children's Hospital. Population controls (n = 578) were frequency-matched to cases by birth year and drawn from the National Birth Registry. Data on surrogate measures of early immune stimulation were collected through in-home interviews. We fitted multivariable models, utilizing targeted causal inference (varimpact), unconditional logistic regression, and latent class analysis (LCA). ResultsIn varimpact analysis, contact with any pet [risk difference (RD) = −0.17, 95% CI: −0.25, −0.10)] or any farm animal (RD = −0.07, 95% CI: −0.13, 0.00) and allergies (RD = −0.08, 95% CI: −0.17, 0.01) were associated with a reduced risk of ALL, whereas experiencing a fever longer than one week was associated with an increased risk (RD = 0.23, 95% CI: 0.12, 0.33). In unconditional logistic regression models, contact with any pet or farm animal and a complete vaccination scheme were inversely associated with odds of ALL (OR = 0.44, 95% CI: 0.31, 0.62; OR = 0.66, 95% CI: 0.49, 0.90; OR = 0.45, 95% CI: 0.24, 0.83; respectively), whereas experiencing a fever longer than one week was positively associated with ALL (OR = 2.44, 95% CI: 1.61, 3.70). Two-class and three-class LCA revealed a group with elevated risk for ALL whose exposure profile was mainly characterized by reduced exposure to pets and farm animals. ConclusionsUsing distinct statistical approaches, we observed that exposure to pets and farm animals was inversely associated with ALL risk, whereas having a fever longer than one week (a putative proxy of severe infection) was associated with an increased risk. For multifactorial diseases such as childhood leukemia, we recommend estimating the joint effects of multiple exposures by applying diverse statistical methods and interpreting their results together. Overall, we found support for the hypothesis that early immune stimulation offers protection against childhood ALL.

Allergies and Childhood Acute Lymphoblastic Leukemia: A Case-Control Study and Meta-analysis.

Background: Allergic disease is suspected to play a role in the development of childhood acute lymphoblastic leukemia (ALL). Studies conducted over the last several decades have yielded mixed results.Methods: We examined the association between allergy, a common immune-mediated disorder, and ALL in the California Childhood Leukemia Study (CCLS), a case-control study of 977 children diagnosed with ALL and 1,037 matched controls (1995-2015). History of allergies in the first year of life was obtained from interviews, mainly reported by mothers. Logistic regression analyses were conducted to estimate ORs and 95% confidence intervals (CIs), controlling for birth order, daycare attendance, and mode of delivery. In addition, we conducted meta-analyses with data from the CCLS and 12 published studies and employed a new method to estimate between-study heterogeneity (R_b).Results: Overall, no associations were observed between childhood ALL risk and specific allergy phenotypes or any allergy, as a group. However, having any allergy was associated with an increased risk of ALL among the youngest study participants. In the meta-analysis random-effects models, reduced odds of ALL were associated with hay fever (metaOR = 0.65; 95% CI, 0.47-0.90); however, restricting the analysis to studies that used medical records for assessment of allergy or recently published studies led to null or attenuated results.Conclusions: Overall, our findings do not support a clear association between allergy and childhood ALL.Impact: The degree to which epidemiologic studies can inform the relationship between allergies and risk of childhood ALL is limited by R_b. Cancer Epidemiol Biomarkers Prev; 27(10); 1142-50. ©2018 AACR.

Maternal Residential Pesticide Use and Risk of Childhood Leukemia in Costa Rica

Evidence suggests that early-life exposure to pesticides inside the home may be associated with childhood leukemia, however data from Latin American countries are limited. We examined whether self-reported maternal residential pesticide use and nearby pesticide applications-before and after child's birth-were associated with acute lymphoblastic leukemia (ALL) in the Costa Rican Childhood Leukemia Study (CRCLS), a population-based case-control study (2001-2003). Cases (n = 251 ALL) were diagnosed between 1995 and 2000 (age <15 years at diagnosis) and were identified through the Costa Rican Cancer Registry and National Children's Hospital. Population controls (n = 577) were drawn from the National Birth Registry. We fitted unconditional logistic regression models adjusted for child sex, birth year, and socioeconomic status to estimate the exposure-outcome associations and also stratified by child sex. We observed that self-reported maternal insecticide use inside the home in the year before pregnancy, during pregnancy, and while breastfeeding was associated with increased odds of ALL among boys [adjusted Odds Ratio (aOR) = 1.63 (95% confidence interval [95% CI]: 1.05-2.53), 1.75 (1.13-2.73), and 1.75 (1.12-2.73), respectively. We also found evidence of exposure-response relationships between more frequent maternal insecticide use inside the home and increased odds of ALL among boys and girls combined. Maternal report of pesticide applications on farms or companies near the home during pregnancy and at any time period were also associated with ALL. Our study in Costa Rica highlights the need for education to minimize pesticide exposures inside and around the home, particularly during pregnancy and breastfeeding.

Maternal residential pesticide use and risk of childhood leukemia in Costa Rica.

Evidence suggests that early‐life exposure to pesticides inside the home may be associated with childhood leukemia, however data from Latin American countries are limited. We examined whether self‐reported maternal residential pesticide use and nearby pesticide applications–before and after child's birth–were associated with acute lymphoblastic leukemia (ALL) in the Costa Rican Childhood Leukemia Study (CRCLS), a population‐based case‐control study (2001‐2003). Cases (n = 251 ALL) were diagnosed between 1995 and 2000 (age <15 years at diagnosis) and were identified through the Costa Rican Cancer Registry and National Children's Hospital. Population controls (n = 577) were drawn from the National Birth Registry. We fitted unconditional logistic regression models adjusted for child sex, birth year, and socioeconomic status to estimate the exposure‐outcome associations and also stratified by child sex. We observed that self‐reported maternal insecticide use inside the home in the year before pregnancy, during pregnancy, and while breastfeeding was associated with increased odds of ALL among boys [adjusted Odds Ratio (aOR) = 1.63 (95% confidence interval [95% CI]: 1.05–2.53), 1.75 (1.13–2.73), and 1.75 (1.12–2.73), respectively. We also found evidence of exposure‐response relationships between more frequent maternal insecticide use inside the home and increased odds of ALL among boys and girls combined. Maternal report of pesticide applications on farms or companies near the home during pregnancy and at any time period were also associated with ALL. Our study in Costa Rica highlights the need for education to minimize pesticide exposures inside and around the home, particularly during pregnancy and breastfeeding.

The Associations of Height-for-Age, Weight-for-Age, and Weight-for-Height With Pediatric Acute Lymphoblastic Leukemia.

Height at diagnosis has been analyzed in connection with acute lymphoblastic leukemia (ALL). Most prior studies have compared cases to national reference data derived from previous birth cohorts. Our objective was to determine the association of height-for-age Z score (HAZ) at time of diagnosis with the odds ratio (OR) of ALL in a case-control study (N=498) with a contemporaneous population of age-matched, sex-matched, and ethnicity-matched controls. We hypothesized that cases would have greater mean HAZ at time of diagnosis/interview, after adjustment for weight-for-age (WAZ) and weight-for-height (WHZ). HAZ was not associated with ALL. For each 1 SD increase in WAZ the OR of ALL was 0.83 (95% confidence interval [CI], 0.68-0.99). The OR of ALL was increased among children who had either a WAZ ≤-2 (OR, 5.10; 95% CI, 1.85-16.75) or WHZ of ≤-2 (OR, 5.27; 95% CI, 1.65-23.61). Previous findings of taller height among ALL cases may arise from the choice of control populations. Children with low WAZ or WHZ were at increased odds of ALL.

Association of atopic diseases and parvovirus B19 with acute lymphoblastic leukemia in childhood and adolescence in the northeast of Brazil.

Several factorsrelated to the immune system, such as a history of allergies and virus infections, may be associated with acute lymphoblastic leukemia (ALL). The purpose of this study was to analyze whether the presence of atopic diseases and previous infection with parvovirus B19 and Epstein-Barr virus (EBV) are associated with the development of ALL. This case-control study was performed in two tertiary hospitals located in northeastern Brazil. The study population included 60 patients who were diagnosed with non-T-cell ALL using myelogram and immunophenotyping and 120 patients in the control group. Atopy was evaluated via a parent questionnaire and medical records. Total immunoglobulin (Ig)E and IgG levels of parvovirus B19 and EBV were measured in the serum. Logistic regression was performed to assess the association between variables and odds of ALL. We identified a significant inverse association between rhinitis, urticaria and elevated IgE serum levels with ALL. A history of parvovirus B19 infection showed a significant association with this type of cancer [OR (95% CI) 2.00 (1.94-4.26); P=0.050]. In logistic regression, the presence of atopy was a protective factor [OR (95% CI) 0.57 (0.38-0.83); P=0.004], and the presence of IgG for parvovirus B19 was an important risk factor for ALL [OR (95% CI) 2.20 (1.02-4.76); P=0.043]. These results suggest that atopic diseases and elevated total IgE levels are associated with a potential protective effect on the development of ALL. Previous infection with parvovirus B19 contributed to ALL susceptibility.

Prenatal exposure to traffic-related air pollution and risk of early childhood cancers.

Exposure to air pollution during pregnancy has been linked to the risk of childhood cancer, but the evidence remains inconclusive. In the present study, we used land use regression modeling to estimate prenatal exposures to traffic exhaust and evaluate the associations with cancer risk in very young children. Participants in the Air Pollution and Childhood Cancers Study who were 5 years of age or younger and diagnosed with cancer between 1988 and 2008 were had their records linked to California birth certificates, and controls were selected from birth certificates. Land use regression-based estimates of exposures to nitric oxide, nitrogen dioxide, and nitrogen oxides were assigned based on birthplace residence and temporally adjusted using routine monitoring station data to evaluate air pollution exposures during specific pregnancy periods. Logistic regression models were adjusted for maternal age, race/ethnicity, educational level, parity, insurance type, and Census-based socioeconomic status, as well as child's sex and birth year. The odds of acute lymphoblastic leukemia increased by 9%, 23%, and 8% for each 25-ppb increase in average nitric oxide, nitrogen dioxide, and nitrogen oxide levels, respectively, over the entire pregnancy. Second- and third-trimester exposures increased the odds of bilateral retinoblastoma. No associations were found for annual average exposures without temporal components or for any other cancer type. These results lend support to a link between prenatal exposure to traffic exhaust and the risk of acute lymphoblastic leukemia and bilateral retinoblastoma.

Infectious Illness in Children Subsequently Diagnosed With Acute Lymphoblastic Leukemia: Modeling the Trends From Birth to Diagnosis

Although there is increasing evidence that immune dysregulation in children who develop acute lymphoblastic leukemia (ALL) is detectable from birth, debate about the role of infectious exposures in infancy continues. With the aim of quantifying children's infectious exposures, investigators have used a number of infection exposure proxies, but there is a lack of consistency in findings, with some markers indicating increased ALL risks and others decreased risks, the disparity being evident both within and between studies. Accordingly, the authors conducted an in-depth analysis of key infection exposure proxies used in the United Kingdom Childhood Cancer Study, a national population-based case-control study conducted over the period 1991-1996, which combined data from medical records, parental interview, and population census. This longitudinal approach revealed the marked deterioration in immune response that emerged around 5 months prior to ALL diagnosis and confirmed that infectious diagnoses in the first year of life were significantly increased (P < 0.05) in children who developed leukemia between 2 and 14 years of age, as well as in those who had birth orders >1, were not breastfed, lived in deprived areas, or were diagnosed with eczema. By contrast, no association between infectious illness and preschool activity was detected, the lower infection levels among controls whose mothers reported attendance contributing to a significantly reduced ALL odds ratio.

Associations between Vaccination and Childhood Cancers in Texas Regions

To determine whether children born in Texas regions with higher vaccination coverage had reduced risk of childhood cancer. The Texas Cancer Registry identified 2800 cases diagnosed from 1995 to 2006 who were (1) born in Texas and (2) diagnosed at ages 2 to 17 years. The state birth certificate data were used to identify 11 200 age- and sex-matched control subjects. A multilevel mixed-effects regression model compared vaccination rates among cases and control subjects at the public health region and county level. Children born in counties with higher hepatitis B vaccine coverage had lower odds of all cancers combined (OR = 0.81, 95% CI: 0.67 to 0.98) and acute lymphoblastic leukemia (ALL) specifically (OR = 0.63, 95% CI: 0.46 to 0.88). A decreased odds for ALL also was associated at the county level with higher rates of the inactivated poliovirus vaccine (OR = 0.67, 95% CI: 0.49 to 0.92) and 4-3-1-3-3 vaccination series (OR = 0.62, 95% CI: 0.44 to 0.87). Children born in public health regions with higher coverage levels of the Haemophilus influenzae type b-conjugate vaccine had lower odds of ALL (OR: 0.58; 95% CI: 0.42 to 0.82). Some common childhood vaccines appear to be protective against ALL at the population level.

Comparison of birth weight corrected for gestational age and birth weight alone in prediction of development of childhood leukemia and central nervous system tumors

High birth weight (HBW) is an established risk factor for childhood acute lymphoblastic leukemia (ALL). The purpose of this study was to evaluate if birth weight (BW) corrected-for-gestational age is a better predictor than BW alone for occurrence of ALL and other malignancies in children. Birth certificate data of 2,254 children with cancer who were younger than 5 years old at diagnosis and registered at Texas Cancer Registry during 1995-2003 were compared to 11,734 age-matched controls. Multivariable logistic regression was used to compare models with BW corrected-for-gestational age and BW alone. Compared to children who were appropriate for gestational age (AGA), children who were large for gestational age (LGA) at birth had a 1.66 times (95% CI 1.32-2.10) higher odds of ALL. Similarly, children with a BW > or =4,000 g had a 1.5 times (95% CI 1.18-1.89) higher odds for ALL, compared to children who weighed >2,500 and <4,000 g at birth. Using model diagnostics, the model containing BW corrected-for-gestational age was a better predictor than the model with BW alone [Akaike's Information Criterion (AIC) 4,646 vs. 4,658, respectively]. Odds ratios (OR) were similar for LGA children who were <4,000 g and LGA children who were > or =4,000 g (OR = 1.5, 95% CI 0.97-2.5 and OR = 1.67, 95% CI 1.29-2.16, respectively). BW was not an independent risk factor for acute myeloid leukemia or brain tumors. BW corrected-for-gestational age is a better predictor than BW alone of risk for ALL. Future studies using BW variable should incorporate gestational age in their analyses.

Increased frequency of mannose-binding lectin insufficiency among children with acute lymphoblastic leukemia

Epidemiological data indicate that acute lymphoblastic leukemia (ALL) could be induced by interactions between the immune system and early childhood infections. Mannose-binding lectin (MBL) plays a critical role in the immune response in early childhood before specific immune protection develops. We investigated whether there may be an association between childhood ALL and low-producing MBL genotypes. Serum MBL levels depend on normal (A) or defective (O) alleles, and on normal (Y) or reduced (X) promoter activities. For this study, 137 noninfants with ALL and 250 controls were classified into 3 MBL genotype groups according to their influence on the serum level of functional MBL: group I, YA/YA and YA/XA (higher levels); group II, XA/XA and YA/O (intermediate levels); and group III, MBL insufficiency with XA/O or O/O (MBL-deficient) genotypes. Compared with controls, cases more often had low-level genotypes (I/II/III: 63 [46%]/44 [32%]/30 [22%] vs 145 [58%]/65 [26%]/40 [16%]; P =.02) and MBL deficiency (8.8% vs 2.8%; P =.009). Thus, the ALL odds ratio for MBL-deficient versus nondeficient individuals was 3.3 (95% CI, 1.3-8.7), whereas the ALL odds ratio for group I versus group II/III genotypes was 0.62 (95% CI, 0.41-0.94). MBL group III patients were significantly younger at diagnosis than patients in group I/II (median, 3.9 vs 5.2 years; P =.04). The study shows that the presence of low-level MBL genotypes is associated with an increased risk of childhood ALL, particularly with early age at onset.

Maternal reproductive history and birth characteristics in childhood acute lymphoblastic leukemia

Using birth-registration data, a case-control study was done to investigate the possible associations of childhood acute lymphoblastic leukemia (ALL) with birth characteristics and maternal reproductive history. The data included cases born and diagnosed in Minnesota since 1969. Matched analyses were conducted using 337 cases and 1336 birth year-matched controls. There was a statistically significant increased odds of ALL for birth to older (greater than 35 years) mothers (odds ratio (OR) = 2.14, 95% confidence interval (CI) = 1.28, 3.58), older fathers (OR = 1.62, 95% CI = 1.14, 2.30), mothers with at least a high school education (OR = 1.61, 95% CI = 1.05, 2.48), and larger intervals (greater than 5 years) between the birth of the proband and the preceding sibling (OR = 1.86, 95% CI = 1.12, 3.09). The increased odds of ALL for birth by Caesarean section approached significance (OR = 1.42, P = 0.06). No overall association was found for: gender, race, paternal education, fetal-loss history, birth order, prenatal care history, pregnancy complications, inducement of labor, multiple birth, gestational age, or birth weight. Age at diagnosis was an important effect modifier of some analyses. For cases diagnosed before age 2 years, there was a 2.7-fold increased odds of ALL if the last pregnancy had resulted in a fetal loss (P = 0.03). For cases diagnosed before age 4 years, birth weight greater than 3800 g was associated with a significant 2.05-fold increased odds of ALL. These data strengthen the hypothesis that prenatal events may play a causative role in childhood ALL, particularly in those cases diagnosed at a younger age.