The Impact of Persistent Leukoencephalopathy on Brain White Matter Microstructure in Long-Term Survivors of Acute Lymphoblastic Leukemia Treated with Chemotherapy Only.

BACKGROUND AND PURPOSE: Survivors of acute lymphoblastic leukemia are at risk for neurocognitive deficits and leukoencephalopathy. We performed a longitudinal assessment of leukoencephalopathy and its associations with long-term brain microstructural white matter integrity and neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia treated on a modern chemotherapy-only protocol. MATERIALS AND METHODS: One hundred seventy-three survivors of acute lymphoblastic leukemia (49% female), treated on a chemotherapy-only protocol, underwent brain MR imaging during active therapy and repeat imaging and neurocognitive testing at follow-up (median, 13.5 years of age; interquartile range, 10.7-17.6 years; median time since diagnosis, 7.5 years; interquartile range, 6.3-9.1 years). Persistence of leukoencephalopathy was examined in relation to demographic and treatment data and to brain DTI in major fiber tracts and neurocognitive testing at follow-up. RESULTS: Leukoencephalopathy was found in 52 of 173 long-term survivors (30.0%) and persisted in 41 of 52 (78.8%) who developed it during therapy. DTI parameters were associated with leukoencephalopathy in multiple brain regions, including the corona radiata (fractional anisotropy, P = .001; mean diffusivity, P < .001), superior longitudinal fasciculi (fractional anisotropy, P = .02; mean diffusivity, P < .001), and superior fronto-occipital fasciculi (fractional anisotropy, P = .006; mean diffusivity, P < .001). Mean diffusivity was associated with neurocognitive impairment including in the genu of the corpus callosum (P = .04), corona radiata (P = .02), and superior fronto-occipital fasciculi (P = .02). CONCLUSIONS: Leukoencephalopathy during active therapy and neurocognitive impairment at long-term follow-up are associated with microstructural white matter integrity. DTI may be more sensitive than standard MR imaging for detection of clinically consequential white matter abnormalities in childhood acute lymphoblastic leukemia survivors treated with chemotherapy and in children undergoing treatment.

Long-term functional outcomes and quality of life in adult survivors of childhood extremity sarcomas: a report from the St. Jude Lifetime Cohort Study.

PURPOSE: This study compared measured physical performance, health-related quality of life (HRQOL), and social role attainment between extremity sarcoma survivors and controls, and evaluated associations between disease and treatment exposures, health conditions, and performance measures. METHODS: Survivors of extremity sarcoma from the St. Jude Lifetime cohort and controls frequency matched by age-, sex-, and race completed physical performance testing and questionnaires. Survivors with Z-scores on outcome measures ≤ -2.0 SD (compared to controls) were categorized with severe impairment/limitation. RESULTS: Among 206 survivors (52.4 % male median age 36 years (range 19-65)), 37 % had low relative lean mass, 9.7 % had an ejection fraction <50 %, 51.5 % had diffusion capacity for carbon monoxide <75 %, 27.7 % had sensory and 25.2 % motor neuropathy, and 78.2 % had musculoskeletal complications. Severe impairments/limitations were present among ≥25 % of survivors on fitness, balance, and physical HRQOL measures, and among ≥15 % on strength and activity of daily living measures. Lower extremity tumor location (OR 8.23, 95 % CI 2.54-26.67, P value 0.0004) and amputation (OR 8.07, 95 % CI 3.06-21.27, P value <0.0001) were associated with poor fitness. Poor fitness was associated with increased odds of scoring <40 on the SF-36 physical component summary (OR 4.83, 95 % CI 1.95-11.99, P value 0.001) and role-physical subscale (OR 3.34, 95 % CI 1.33-8.43, P value 0.01). Survivors and controls had similar rates of marriage, independent living, employment, and college attendance. CONCLUSIONS: Extremity sarcoma survivors experience high rates of physical impairment and report lower than expected physical HRQOL. However, they are as likely as peers to be married, live independently, be employed, and attend college. IMPLICATIONS FOR CANCER SURVIVORS: Follow-up for extremity sarcoma survivors should include assessment of need for further orthopedic care and rehabilitation to address cardiopulmonary and musculoskeletal health.

A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus.

Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR)=0.81, 95% confidence interval (95% CI) = 0.76-0.86, P(combined) = 3.5 × 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B- and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.

Male infertility in long-term survivors of pediatric cancer: a report from the childhood cancer survivor study.

PURPOSE: The purpose of this study was to assess the prevalence of male infertility and treatment-related risk factors in childhood cancer survivors. METHODS: Within the Childhood Cancer Survivor Study, 1,622 survivors and 274 siblings completed the Male Health Questionnaire. The analysis was restricted to survivors (938/1,622; 57.8 %) and siblings (174/274; 63.5 %) who tried to become pregnant. Relative risks (RR) and 95 % confidence intervals (CI) for the prevalence of self-reported infertility were calculated using generalized linear models for demographic variables and treatment-related factors to account for correlation among survivors and siblings of the same family. All statistical tests were two-sided. RESULTS: Among those who provided self-report data, the prevalence of infertility was 46.0 % in survivors versus 17.5 % in siblings (RR = 2.64, 95 % CI 1.88-3.70, p < 0.001). Of survivors who met the definition for infertility, 37 % had reported at least one pregnancy with a female partner that resulted in a live birth. In a multivariable analysis, risk factors for infertility included an alkylating agent dose (AAD) score ≥3 (RR = 2.13, 95 % CI 1.69-2.68 for AAD ≥3 versus AAD <3), surgical excision of any organ of the genital tract (RR = 1.63, 95 % CI 1.20-2.21), testicular radiation ≥4 Gy (RR = 1.99, 95 % CI 1.52-2.61), and exposure to bleomycin (RR = 1.55, 95 % CI 1.20-2.01). CONCLUSION: Many survivors who experience infertility father their own children, suggesting episodes of both fertility and infertility. This and the novel association of infertility with bleomycin warrant further investigation. IMPLICATIONS FOR CANCER SURVIVORS: Though infertility is common, male survivors reporting infertility often father their own children. Bleomycin may pose some fertility risk.

Bone mineral density among long-term survivors of childhood acute lymphoblastic leukemia: results from the St. Jude Lifetime Cohort Study.

BACKGROUND: The prevalence of low bone mineral density (BMD) in adult survivors of childhood acute lymphoblastic leukemia (ALL), and the degree of recovery or decline, are not well elucidated. PROCEDURE: Study subjects (age ≥ 18 years and ≥10 years post-diagnosis) participated in an institutional follow-up protocol and risk-based clinical evaluation based on Children's Oncology Group guidelines. Trabecular volumetric BMD was ascertained using quantitative computed tomography, reported as age- and sex-specific Z-scores. RESULTS: At median age 31 years, 5.7% of 845 subjects had a BMD Z-score of ≤-2 and 23.8% had a Z-score of -1 to -2. Cranial radiation dose of ≥24 Gy, but not cumulative methotrexate or prednisone equivalence doses, was associated with a twofold elevated risk of a BMD Z-score of ≤-1. The cranial radiation effect was stronger in females than in males. In a subset of 400 subjects, 67% of those who previously had a BMD Z-score of ≤-2 improved by one or more categories a median of 8.5 years later. CONCLUSIONS: Very low BMD was relatively uncommon in this sample of adult survivors of childhood ALL, and BMD Z-scores tended to improve from adolescence to young adulthood. High-dose cranial or craniospinal radiation exposure was the primary predictor of suboptimal BMD in our study. Given that cranial radiation treatment for childhood ALL is used far more sparingly now than in earlier treatment eras, concerns about persistently low BMD among most current childhood ALL patients may be unwarranted.

Longitudinal patterns of psychological distress in adult survivors of childhood cancer.

BACKGROUND: This study investigated longitudinal patterns of psychological distress in adult survivors of childhood cancer. METHODS: Participants included 4569 adult survivors in the Childhood Cancer Survivor Study Cohort (CCSS) who completed the Brief Symptom Inventory-18 on three occasions between 1994 and 2010. Longitudinal latent class analysis was used to identify discrete classes of psychological distress. Predictors of class membership were examined through logistic regression modelling with odds ratios (ORs) and 95% confidence intervals (CIs) reported. RESULTS: Survivors were a median of 39 years of age and 30 years from diagnosis at the most recent follow-up. Most survivors reported few or no symptoms of distress over time, although subsets of survivors reported persistently elevated (depression: 8.9%; anxiety: 4.8%; somatisation: 7.2%) or significant increases in distress symptoms over the follow-up period (depression: 10.2%; anxiety: 11.8%; somatisation: 13.0%). Increasing distress symptoms were predicted by survivor perception of worsening physical health over time (depression: OR=3.3; 95% CI=2.4-4.5; anxiety: OR=3.0; 95% CI=2.2-4.0; somatisation: OR=5.3; 95% CI=3.9-7.4). Persistent distress symptoms were also predicted by survivor perception of worsening physical health over time, as well as by worsening pain and ending analgesic use. CONCLUSION: Subgroups of adult survivors are at-risk for chronic distress or significant increases in distress decades following their original cancer diagnosis. Routine screening of psychological distress in adult survivors of childhood cancer is warranted, especially for survivors who experience physical health morbidities.

Melanoma as a subsequent neoplasm in adult survivors of childhood cancer: a report from the childhood cancer survivor study.

BACKGROUND: Childhood cancer survivors have a sixfold increased risk of developing subsequent neoplasms when compared to the general population. We sought to describe the occurrence of melanoma as a subsequent neoplasm among adult survivors of childhood cancer. PATIENTS AND METHODS: Among 14,358 5-year survivors of childhood cancer diagnosed between 1970 and 1986, we calculated the cumulative incidence, standardized incidence ratio (SIR), and absolute excess risk (AER) of subsequent melanoma. Potential risk factors were assessed using a cause-specific hazards model. RESULTS: Fifty-seven melanomas (46 invasive, 2 ocular, and 9 in situ) occurred in 51 survivors. The median time to the development of melanoma was 21.0 years (range: 5.6-35.4 years) and the median age at melanoma was 32.3 years (range: 10.9-49.0 years). Initial cancer diagnoses included soft tissue and bone sarcoma (n = 15), leukemia (13), lymphoma (14), central nervous system malignancy (5), Wilms tumor (3), and neuroblastoma (1). The cumulative incidence of first subsequent melanoma at 35 years from initial cancer diagnosis was 0.55% [95% confidence interval (CI): 0.37-0.73]. The SIR of subsequent invasive malignant melanoma of the skin was 2.42 (95% CI: 1.77-3.23), and the AER was 0.10 (95% CI: 0.05-0.15) per 1,000 person-years. No statistically significant associations were found between melanoma risk and family history of cancer, demographic, or treatment-related factors. CONCLUSION: Survivors of childhood cancer have an approximate 2.5-fold increased risk of melanoma. Early screening and prevention strategies are warranted.

Extremely low-frequency magnetic fields and survival from childhood acute lymphoblastic leukemia: an international follow-up study.

A previous US study reported poorer survival in children with acute lymphoblastic leukemia (ALL) exposed to extremely low-frequency magnetic fields (ELF-MF) above 0.3 µT, but based on small numbers. Data from 3073 cases of childhood ALL were pooled from prospective studies conducted in Canada, Denmark, Germany, Japan, UK and US to determine death or relapse up to 10 years from diagnosis. Adjusting for known prognostic factors, we calculated hazard ratios (HRs) and 95% confidence intervals (CI) for overall survival and event-free survival for ELF-MF exposure categories and by 0.1 µT increases. The HRs by 0.1 µT increases were 1.00 (CI, 0.93-1.07) for event-free survival analysis and 1.04 (CI, 0.97-1.11) for overall survival. ALL cases exposed to >0.3 µT did not have a poorer event-free survival (HR=0.76; CI, 0.44-1.33) or overall survival (HR=0.96; CI, 0.49-1.89). HRs varied little by subtype of ALL. In conclusion, ELF-MF exposure has no impact on the survival probability or risk of relapse in children with ALL.

Analgesic use during pregnancy and risk of infant leukaemia: a Children's Oncology Group study.

BACKGROUND: Infant leukaemia is likely initiated in utero. METHODS: We examined whether analgesic use during pregnancy was associated with risk by completing telephone interviews of the mothers of 441 infant leukaemia cases and 323 frequency-matched controls, using unconditional logistic regression. RESULTS: With the exception of a reduced risk for infant acute myeloid leukaemias with non-aspirin non-steroidal anti-inflammatory drugs (NSAID) use early in pregnancy (odds ratios=0.60; confidence intervals: 0.37-0.97), no statistically significant associations were observed for aspirin, non-aspirin NSAIDs, or acetaminophen use in early pregnancy or after knowledge of pregnancy. CONCLUSION: Overall, analgesic use during pregnancy was not significantly associated with the risk of infant leukaemia.

Paediatric germ cell tumours and congenital abnormalities: a Children's Oncology Group study.

METHODS: Maternally reported congenital abnormalities (CAs) were examined in a case-control study of 278 cases of paediatric germ cell tumours (GCTs) and 423 controls. RESULTS AND CONCLUSIONS: Germ cell tumours were significantly associated with cryptorchidism in males (OR=10.8, 95% CI: 2.1-55.1), but not with any other specific CA in either sex.

Maternal hemoglobin concentration during pregnancy and risk of infant leukaemia: a children's oncology group study.

In contrast to the positive association found in three studies between maternal anaemia during pregnancy and childhood leukaemia, no such association was found in infant leukaemia (odds ratio 0.85, 95% confidence interval 0.53-1.37).

Prevalence of conception and pregnancy outcomes after hematopoietic cell transplantation: report from the Bone Marrow Transplant Survivor Study.

We conducted a retrospective study to describe the magnitude of compromise in reproductive function and investigate pregnancy outcomes in 619 women and partners of men treated with autologous (n=241) or allogeneic (n=378) hematopoietic cell transplantation (HCT) between 21 and 45 years of age, and surviving 2 or more years. Median age at HCT was 33.3 years and median time since HCT 7.7 years. Mailed questionnaires captured pregnancies and their outcomes (live birth, stillbirth, miscarriage). Thirty-four patients reported 54 pregnancies after HCT (26 males, 40 pregnancies; eight females, 14 pregnancies), of which 46 resulted in live births. Factors associated with reporting no conception included older age at HCT (> or =30 years: odds ratio (OR)=4.8), female sex (OR=3.0), and total body irradiation (OR=3.3). Prevalence of conception and pregnancy outcomes in HCT survivors were compared to those of 301 nearest-age siblings. Although the risk for not reporting a conception was significantly increased among HCT survivors (OR=36), survivors were not significantly more likely than siblings to report miscarriage or stillbirth (OR=0.7). Although prevalence of conception is diminished after HCT, if pregnancy does occur, outcome is likely to be favorable. Patients should be counseled prior to transplant regarding strategies to preserve fertility.

Childhood and maternal infections and risk of acute leukaemia in children with Down syndrome: a report from the Children's Oncology Group.

Children with Down syndrome (DS) are highly susceptible to acute leukaemia. Given the potential role of infections in the aetiology of leukaemia in children without DS, we investigated whether there was an association between early-life infections and acute leukaemia in children with DS. Maternal infections during pregnancy were also examined. We enrolled 158 incident cases of acute leukaemia in children with DS (97 acute lymphoblastic leukaemia (ALL) and 61 acute myeloid leukaemia (AML)) diagnosed at Children's Oncology Group institutions between 1997 and 2002. DS controls (N=173) were selected from the cases' primary care clinics and frequency matched on age at leukaemia diagnosis. Data were collected on demographics, child's medical history, mother's medical history, and other factors by maternal interview. Analyses were conducted using unconditional logistic regression adjusted for potential confounders. A significant negative association was observed between acute leukaemia and any infection in the first 2 years of life (adjusted odds ratio (OR)=0.55, 95% confidence interval (CI) (0.33-0.92); OR=0.53, 95% CI (0.29-0.97); and OR=0.59, 95% CI (0.28-1.25) for acute leukaemia combined, ALL, and AML respectively). The association between acute leukaemia and maternal infections during pregnancy was in the same direction but not significant. This study offers support for the hypothesis that early-life infections may play a protective role in the aetiology of acute leukaemia in children with DS.

Function and quality-of-life of survivors of pelvic and lower extremity osteosarcoma and Ewing's sarcoma: the Childhood Cancer Survivor Study.

Limb-sparing surgeries have been performed more frequently than amputation based on the belief that limb-sparing surgeries provide improved function and quality-of-life (QOL). However, this has not been extensively studied in the paediatric population, which has unique characteristics that have implications for function and QOL. Using the Childhood Cancer Survivor Study, 528 adult long-term survivors of pediatric lower extremity bone tumours, diagnosed between 1970 and 1986, were contacted and completed questionnaries assessing function and QOL. Survivors were an average of 21 years from diagnosis with an average age of 35 years. Overall they reported excellent function and QOL. Compared to those who had a limb-sparing procedure, amputees were not more likely to have lower function and QOL scores and self-perception of disability included general health status, lower educational attainment, older age and female gender. Findings from this study suggest that, over time, amputees do as well as those who underwent limb-sparing surgeries between 1970 and 1986. However, female gender, lower educational attainment and older current age appear to influence function, QOL and disability.

RAS oncogene mutations and outcome of therapy for childhood acute lymphoblastic leukemia.

Activating mutations in the RAS oncogenes are among the most common genetic alterations in human cancers, including patients with acute lymphoblastic leukemia (ALL). We sought to define the frequency and spectrum, and possible prognostic importance, of N- and K-RAS mutations in children with ALL treated with contemporary therapy. Leukemic blast DNA from 870 children was analyzed for the presence of activating mutations in the N- or K-RAS oncogenes using a sensitive mutation detection algorithm. RAS mutations were present in the blasts of 131 (15.1%) pediatric ALL patients. The spectrum of mutations included 81 (9.3%) mutations of codons 12/13 of N-RAS, 12 (1.4%) mutations of codon 61 of N-RAS, 39 (4.5%) mutations of codons 12/13 of K-RAS, and 2 (0.2%) mutations of codon 61 of K-RAS. The presence of N- or K-RAS mutations was not associated with white blood cell count at diagnosis, sex, race, extramedullary testicular involvement, central nervous system disease, or NCI/CTEP ALL Risk Group. Patients with an exon 1 K-RAS mutation (codons 12/13) were significantly younger at diagnosis (P=0.001) and less frequently B-lineage phenotype (P=0.01). RAS mutation status did not predict overall survival, event-free survival and disease-free survival. While N- and K-RAS mutations can be identified in 15% of children with newly diagnosed ALL, they do not represent a significant risk factor for outcome using contemporary chemotherapy regimens.

Pet ownership and childhood acute leukemia (USA and Canada).

OBJECTIVES: For more than three decades there has been speculation regarding a possible role of zoonotic diseases in the development of human leukemia. This study investigated the potential relationship between exposure to pets and the development of childhood leukemia. METHODS: Data from 2359 cases of acute leukemia from two large case-control studies were analyzed. Cases were individually matched to population controls on telephone exchange, age, and race. Conditional logistic regression was used to estimate odds ratios (OR) associated with pet ownership. RESULTS: Overall, there was no association between pet ownership (either "any pet", dog, or cat) and childhood acute leukemia (OR(any pet:) = 1.01, 95% CI 0.89-1.2). Additionally, no relationship was found between exposure to an ill pet and childhood leukemia. CONCLUSION: The results of this analysis suggest that pet ownership (healthy or sick) is unrelated to an increased risk of childhood leukemia.

Late mortality experience in five-year survivors of childhood and adolescent cancer: the Childhood Cancer Survivor Study.

PURPOSE: Survivors of childhood and adolescent cancer are at risk for long-term effects of disease and treatment. The Childhood Cancer Survivor Study assessed overall and cause-specific mortality in a retrospective cohort of 20,227 5-year survivors. PATIENTS AND METHODS: Eligible subjects were individuals diagnosed with cancer (from 1970 to 1986) before the age of 21 who had survived 5 years from diagnosis. Underlying cause of death was obtained from death certificates and other sources and coded and categorized as recurrent disease, sequelae of cancer treatment, or non-cancer-related. Age and sex standardized mortality ratios (SMRs) were calculated using United States population mortality data. RESULTS: The cohort, including 208,947 person-years of follow-up, demonstrated a 10.8-fold excess in overall mortality (95% confidence interval, 10.3 to 11.3). Risk of death was statistically significantly higher in females (SMR = 18.2), individuals diagnosed with cancer before the age of 5 years (SMR = 14.0), and those with an initial diagnosis of leukemia (SMR = 15.5) or CNS tumor (SMR = 15.7). Recurrence of the original cancer was the leading cause of death among 5-year survivors, accounting for 67% of deaths. Statistically significant excess mortality rates were seen due to subsequent malignancies (SMR = 19.4), along with cardiac (SMR = 8.2), pulmonary (SMR = 9.2), and other causes (SMR = 3.3). Treatment-related associations were present for subsequent cancer mortality (radiation, alkylating agents, epipodophyllotoxins), cardiac mortality (chest irradiation, bleomycin), and other deaths (radiation, anthracyclines). No excess mortality was observed for external causes (SMR = 0.8). CONCLUSION: While recurrent disease remains a major contributor to late mortality in 5-year survivors of childhood cancer, significant excesses in mortality risk associated with treatment-related complications exist up to 25 years after the initial cancer diagnosis.

Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study.

BACKGROUND: Because survival rates among childhood cancer patients are increasing, assessing the risk of second and subsequent malignant neoplasms (SMNs) is ever more important. Using the Childhood Cancer Survivor Study cohort, we identified the risk of SMNS: METHODS: A retrospective cohort of 13 581 children diagnosed with common cancers before age 21 years and surviving at least 5 years was constructed with the use of data from patients treated at 25 U.S. and Canadian institutions. SMNs were ascertained through self-administered questionnaires and verified by pathology reports. Information on therapeutic exposures was abstracted from medical records. The risk of SMN was evaluated by standardized incidence ratios (SIRs) and excess absolute risk. Poisson multiple regression models were used to assess the impact of host and therapy factors on the risk of developing SMNS: All statistical tests were two-sided. RESULTS: In 298 individuals, 314 SMNs were identified (SIR = 6.38; 95% confidence interval [CI] = 5.69 to 7.13). The largest observed excess SMNs were bone and breast cancers (SIR = 19.14 [95% CI = 12.72 to 27.67] and SIR = 16.18 [95% CI = 12.35 to 20.83], respectively). A statistically significant excess of SMNs followed all childhood cancers. In multivariate regression models adjusted for therapeutic radiation exposure, SMNs of any type were independently associated with female sex (P<.001), childhood cancer at a younger age (P for trend <.001), childhood Hodgkin's disease or soft-tissue sarcoma (P<.001 and P =.01, respectively), and exposure to alkylating agents (P for trend =.02). Twenty years after the childhood cancer diagnosis, the cumulative estimated SMN incidence was 3.2%. However, only 1.88 excess malignancies occurred per 1000 years of patient follow-up. CONCLUSIONS: Success in treating children with cancer should not be overshadowed by the incidence of SMNS: However, patients and health-care providers must be aware of risk factors for SMNs so that surveillance is focused and early prevention strategies are implemented.

Household solvent exposures and childhood acute lymphoblastic leukemia.

OBJECTIVES: This study explored the risk of childhood acute lymphoblastic leukemia (ALL) associated with participation by household members in hobbies or other home projects involving organic solvents. METHODS: Participants in this case-control study were 640 subjects with ALL and 640 matched controls. RESULTS: Childhood ALL was associated with frequent (> 4 times/month) exposure to model building (odds ratio [OR] = 1.9; 95% confidence interval [95% CI] = 0.7, 5.8) and artwork using solvents (OR = 4.1; 95% CI = 1.1, 15.1). We also found elevated risk (OR = 1.7; 95% CI = 1.1, 2.7) among children whose mothers lived in homes painted extensively (> 4 rooms) in the year before the children's birth. CONCLUSIONS: In this exploratory study, substantial participation by household members in some common household activities that involve organic solvents was associated with elevated risks of childhood ALL.