Optimal treatment for Philadelphia-negative acute lymphoblastic leukemia in first remission in the era of high-intensity chemotherapy.

The optimal treatment for Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR1) has not been established in the high-intensity chemotherapy era. The outcomes of patients with Ph-negative ALL who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched related or unrelated donor in CR1 (HSCT-MRD group and HSCT-MUD group) were obtained from a Japanese registry database. Patients aged 16-24 years and 25-65 years were analyzed separately, and their outcomes were compared to those of patients who continued high-intensity chemotherapy in CR1 in studies (202U group and 202O group) by the Japan Adult Leukemia Study Group (JALSG). In the HSCT-MRD group, patients younger than 25 years had lower overall survival (OS) than the 202U group, presumably due to the higher non-relapse mortality (NRM) in the HSCT-MRD group. Patients 25 years and older had similar OS to the 202O group. The lower relapse rate was counterbalanced by higher NRM in the HSCT-MRD group. In the HSCT-MUD group, patients in both age groups had similar OS to their corresponding groups in the JALSG studies. In conclusion, high-intensity chemotherapy may change the role of HSCT for Ph-negative ALL.

New Approaches to Treating Challenging Subtypes of ALL in AYA Patients.

PURPOSE OF REVIEW: The treatment of acute lymphoblastic leukemia (ALL) in adolescent and young adult (AYA) patients has markedly improved with the adoption of pediatric-inspired protocols. However, there remain several subtypes of ALL that represent significant therapeutic challenges. Here, we review the current evidence guiding treatment of Philadelphia chromosome-positive (Ph+), Philadelphia chromosome-like (Ph-L), and early T-precursor (ETP) ALL in the AYA population. RECENT FINDINGS: Clinical trials in Ph + ALL have demonstrated the superior efficacy of second- and third-generation tyrosine kinase inhibitors (TKIs) to induce and maintain remission. Current efforts now focus on determining the durability of these remissions and which patients will benefit from transplant. For Ph-like and ETP ALL, recent studies are investigating the addition of novel agents to standard treatment. The treatment of Ph + ALL has significantly improved with the addition of potent TKIs. However, the treatment of Ph-like and ETP ALL remains a challenge. At this time, the judicious use of allogenic transplant is the only current approach to modify this increased risk.

Coffee intake during pregnancy and childhood acute leukemia - A cohort study.

OBJECTIVES: To estimate a possible association between coffee intake during pregnancy and risk of childhood acute leukemia by using a cohort design. METHODS: We included data from two birth cohorts; the Danish National Birth Cohort and the Aarhus Birth Cohort. Recruitment of 141,216 eligible pregnancies occurred from 1 August 1989 to 31 December 2012. Information on maternal prenatal coffee intake and covariates was collected in early second trimester of pregnancy. Information on childhood AL diagnosed in offspring was obtained from the Danish National Patient Register. We used competing risk time-to-event regression analysis, using the pseudo-observation method to estimate risk ratio (RR) with no coffee intake during pregnancy considered the reference group. RESULTS: In total 96 children were diagnosed with AL, hereof 73 with acute lymphoblastic leukemia (ALL). Coffee intake of 0.5-3 cups/day during pregnancy was not associated with a higher risk of childhood AL; aRR = 0.89, 95 % confidence interval (CI): 0.48, 1.65, however, an intake of >3 cups/day resulted in aRR = 1.37, 95 % CI: 0.56, 3.32. Only including ALL as outcome we found similar results; aRR = 0.80, 95 % CI: 0.37-1.74 and aRR = 1.46 95 % CI: 0.52-4.09, respectively. CONCLUSION: We found no significant association between maternal coffee intake and risk of childhood AL but the number of cases was limited. The confidence limits does not exclude that a high prenatal coffee intake may increase the risk of childhood AL and larger studies based on prospective data are needed.

Novel ETV6-RUNX1 Mouse Model to Study the Role of ELF-MF in Childhood B-Acute Lymphoblastic Leukemia: a Pilot Study.

Exposure to extremely low-frequency magnetic fields (ELF-MFs) has been classified by the International Agency for Research on Cancer (IARC) as "possibly carcinogenic to humans," based on limited scientific evidence concerning childhood leukemia. This assessment emphasized the lack of appropriate animal models recapitulating the natural history of this disease. Childhood B-cell acute lymphoblastic leukemia (B-ALL) is the result of complex interactions between genetic susceptibility and exposure to exogenous agents. The most common chromosomal alteration is the ETV6-RUNX1 fusion gene, which confers a low risk of developing the malignancy by originating a preleukemic clone requiring secondary hits for full-blown disease to appear. To develop potential prophylactic interventions, we need to identify the environmental triggers of the second hit. Recently, we generated a B-ALL mouse model of the human ETV6-RUNX1+ preleukemic state. Here, we present the results from the ARIMMORA pilot study, obtained by exposing 34 Sca1-ETV6-RUNX1 mice (vs. 27 unexposed) to a 50 Hz magnetic field of 1.5 mT with both fundamental and harmonic content, with an on/off cycle of 10 min/5 min, for 20 h/day, from conception until 3 months of age. Mice were monitored until 2 years of age and peripheral blood was periodically analyzed by flow cytometry. One of the exposed mice developed B-ALL while none of the non-exposed did. Although the results are statistically non-significant due to the limited number of mice used in this pilot experiment, overall, the results show that the newly developed Sca1-ETV6-RUNX1 mouse can be successfully used for ELF-MF exposure studies about the etiology of childhood B-ALL. Bioelectromagnetics. 2019;40:343-353. © 2019 Bioelectromagnetics Society.

Association of maternal and index child's diet with subsequent leukemia risk: A systematic review and meta analysis.

BACKGROUND: Exploring the effect of maternal and/or childhood diet on offspring leukemogenesis is challenging, given differences in food group categories, their potentially variable impact depending on time window of exposure and the multiple leukemia subtypes. We opted to quantitatively synthesize published data on the association of maternal/child diet with leukemia risk. METHODS: Medline was searched until June 30th, 2016 for eligible articles on the association of childhood leukemia with consumption of (i) food groups, excluding alcoholic and non-alcoholic beverages, and (ii) specific dietary supplements before/during index pregnancy and childhood. RESULTS: Eighteen studies of case-control design (N=11,720 cases/18,721 controls) were included, of which nine assessed maternal dietary components, five index child's and four both, mainly focusing on acute lymphoblastic leukemia (ALL). Statistically significant inverse estimates for ALL were found (2 studies, 413 cases, 490 controls) for fruit (OR: 0.81, 95% CI: 0.67, 0.99); vegetables (OR: 0.51, 95% CI: 0.28, 0.94); legumes (OR: 0.76, 95% CI: 0.62, 0.94); fish (OR: 0.27, 95% CI: 0.14, 0.53, among the 0-4year old; 2 studies 215 cases, 215 controls); preconception folic acid supplementation (OR: 0.69, 95%CI: 0.50-0.95; published meta analysis plus 2 studies, 3511 cases, 6816 controls); and use of vitamins during pregnancy (OR: 0.81, 95%CI: 0.74-0.88; published meta analysis plus one study, 5967 cases, 8876 controls). The associations (2 studies) of the remaining food groups and maternal dietary supplements consumption during pregnancy as well as of childhood diet and supplements intake (2-4 studies) were non significant. CONCLUSIONS: Maternal consumption of specific food groups comprising"healthy" items of the Mediterranean diet, preconception use of folic acid and intake of vitamins during pregnancy were associated with decreased ALL risk. Further research is needed, however preferably with homogeneous dietary information and data on immunophenotypic/cytogenetic subtypes to also explore the interaction of specific macro- and micronutrients intake with gene polymorphisms.

Childhood Leukemia: A Preventable Disease.

In contrast to most pediatric cancers, there is a growing body of literature, nationally and internationally, that has implicated the role of several environmental indoor and outdoor hazards in the etiology of childhood leukemia. For example, exposures to solvents, traffic, pesticides, and tobacco smoke have consistently demonstrated positive associations with the risk of developing childhood leukemia. Intake of vitamins and folate supplementation during the preconception period or pregnancy has been demonstrated to have a protective effect. Despite the strength of these findings, the dissemination of this knowledge to clinicians has been limited. Some children may be more vulnerable than others as documented by the high and increasing incidence of childhood leukemia in Hispanics. To protect children's health, it is prudent to establish programs to alter exposure to those factors with well-established associations with leukemia risk rather than to suspend judgment until no uncertainty remains. This is particularly true because other serious health outcomes (both negative and positive) have been associated with the same exposures. We draw from historical examples to put in perspective the arguments of association versus causation, as well as to discuss benefits versus risks of immediate and long-term preventive actions.

Maternal diet quality before pregnancy and risk of childhood leukaemia.

Previous studies on maternal nutrition and childhood leukaemia risk have focused on the role of specific nutrients such as folate and have not considered broader measures of diet quality, which may better capture intake of diverse nutrients known to impact fetal development. We examined the relationship between maternal diet quality before pregnancy, as summarised by a diet quality index, and risk of childhood acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in a case-control study in California. Dietary intake in the year before pregnancy was assessed using FFQ in 681 ALL cases, 103 AML cases and 1076 matched controls. Conditional logistic regression was used to estimate OR and 95 % CI for diet quality continuous score and quartiles (Q1-Q4). Higher maternal diet quality score was associated with reduced risk of ALL (OR 0·66; 95 % CI 0·47, 0·93 for Q4 v. Q1) and possibly AML (OR 0·42; 95 % CI 0·15, 1·15 for Q4 v. Q1). No single index component appeared to account for the association. The association of maternal diet quality with risk of ALL was stronger in children diagnosed under the age of 5 years and in children of women who did not report using vitamin supplements before pregnancy. These findings suggest that the joint effects of many dietary components may be important in influencing childhood leukaemia risk.

Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood acute lymphoblastic leukemia.

BACKGROUND: Several studies suggest that maternal folic acid supplementation before or during pregnancy protects against childhood acute lymphoblastic leukemia (ALL). We investigated associations between ALL risk and folate pathway gene polymorphisms, and their modification by maternal folic acid supplements, in a population-based case-control study (2003-2007). METHODS: All Australian pediatric oncology centers provided cases; controls were recruited by national random digit dialing. Data from 392 cases and 535 controls were included. Seven folate pathway gene polymorphisms (MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, MTR 2756 A>G, MTR 5049 C>A, CBS 844 Ins68, and CBS 2199 T>C) were genotyped in children and their parents. Information on prepregnancy maternal folic acid supplement use was collected. ORs were estimated with unconditional logistic regression adjusted for frequency-matched variables and potential confounders. Case-parent trios were also analyzed. RESULTS: There was some evidence of a reduced risk of ALL among children who had, or whose father had, the MTRR 66GG genotype: ORs 0.60 [95% confidence interval (CI) 0.39-0.91] and 0.64 (95% CI, 0.40-1.03), respectively. The ORs for paternal MTHFR 677CT and TT genotypes were 1.41 (95% CI, 1.02-1.93) and 1.81 (95% CI, 1.06-3.07). ORs varied little by maternal folic acid supplementation. CONCLUSIONS: Some folate pathway gene polymorphisms in the child or a parent may influence ALL risk. While biologically plausible, underlying mechanisms for these associations need further elucidation. IMPACT: Folate pathway polymorphisms may be related to risk of childhood ALL, but larger studies are needed for conclusive results.

Paternal intake of folate and vitamins B6 and B12 before conception and risk of childhood acute lymphoblastic leukemia.

PURPOSE: We investigated whether paternal dietary intake of folate before conception is associated with the risk of childhood acute lymphoblastic leukemia (ALL) in a nationwide case-control study. METHODS: Data on dietary folate intake during the 6 months before the child's conception were collected from 285 case fathers and 595 control fathers using a dietary questionnaire. Nutrient intake was quantified using a customized computer software package based on Australian food composition databases. Data on folate intake were analyzed using unconditional logistic regression, adjusting for study-matching variables, total energy, and potentially confounding variables. In a subset of 229 cases and 420 controls, data on vitamin B6 and vitamin B12 intake were also analyzed. RESULTS: No consistent associations were seen with paternal dietary intake of folate or vitamin B6. Higher levels of paternal dietary vitamin B12 were appeared to be associated with an increased risk of childhood ALL, with those in the highest tertile of consumption having an OR of 1.51 (0.97, 2.36). The use of supplements containing folate and vitamins B6 or B12 was rare. CONCLUSIONS: We did not find any biologically plausible evidence that paternal nutrition in the period leading up to conception was associated with childhood ALL. Our finding for vitamin B12 may be a chance finding, given the number of analyses performed, or be attributable to participation bias because parents with a tertiary education had the lowest level of B12 intake and tertiary education was more common among control than case parents.

Risk of leukemia in relation to exposure to ambient air toxics in pregnancy and early childhood.

There are few established causes of leukemia, the most common type of cancer in children. Studies in adults suggest a role for specific environmental agents, but little is known about any effect from exposures in pregnancy to toxics in ambient air. In our case-control study, we ascertained 69 cases of acute lymphoblastic leukemia (ALL) and 46 cases of acute myeloid leukemia (AML) from California Cancer Registry records of children

Gene-environment interactions and the risk of childhood acute lymphoblastic leukemia: exploring the role of maternal folate genes and folic Acid fortification.

Few studies have evaluated the interaction of folic acid fortification and folate metabolic genes on the risk of childhood acute lymphoblastic leukemia (ALL). Because folate status is influenced by both intake and genetic variation, the objective of this study was to explore maternal folate metabolic gene-folic acid fortification interactions and the risk of childhood ALL. The study population consisted of 120 ALL case-parent triads recruited from Texas Children's Cancer Center between 2003 and 2010. For this analysis, we focused on 13 maternal single nucleotide polymorphisms (SNPs) in 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). Prefortification was defined as delivery before January 1997 and postfortification as delivery in or after January 1997. We used a two-step approach to evaluate gene-environment interactions. First, a case-only approach was used, as this design provides greater power in the assessment of gene-environment interactions compared to other approaches. Second, we confirmed all statistically significant interactions using a log-linear approach among case-parent triads. Only one of 13 interactions evaluated was confirmed in step 2. Specifically, mothers with the minor allele of MTR rs1804742 and who delivered during the prefortification period were at a greater risk of having a child with ALL (OR = 1.54, 95% CI: 0.82-2.88), compared to those mothers who delivered during the postfortification period (OR = 0.81, 95% CI: 0.22-2.99, P for interaction = .03). In one of the few studies to evaluate maternal folate metabolic genotype-folic acid interactions, we found limited evidence that the maternal MTR rs1804742 appeared to interact with higher folic acid levels to influence childhood ALL risk.

Maternal coffee consumption during pregnancy and risk of childhood acute leukemia: a metaanalysis.

OBJECTIVE: This study was undertaken to explore the association between maternal coffee consumption during pregnancy and childhood acute leukemia (AL). STUDY DESIGN: The PubMed database was used to search studies up to May 5, 2013, and the lists of references of retrieved articles were also screened to identify additional relevant studies. Studies were included if they reported the odds ratio and corresponding 95% confidence interval (CI) of childhood AL, including childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), with respect to maternal coffee consumption during pregnancy. RESULTS: Compared with non/lowest drinkers, the combined odds ratio regarding the relationship of maternal coffee consumption during pregnancy and childhood AL was 1.22 (95% CI, 1.04-1.43) for ever drinkers, 1.16 (95% CI, 1.00-1.34) for low to moderate-level drinkers, and 1.72 (95% CI, 1.37-2.16) for high-level drinkers. When analysis was conducted by subtypes of childhood AL, maternal coffee consumption (high-level drinkers vs non/lowest drinkers) was statistically significantly associated with childhood ALL (1.65; 95% CI, 1.28-2.12) and childhood AML (1.58; 95% CI, 1.20-2.08). We observed the linear dose-response relationship of coffee consumption and childhood AL (P for nonlinearity = .68), including childhood ALL and childhood AML; with increased coffee consumption, the risk of childhood AL increased. CONCLUSION: The findings of the metaanalysis suggest that maternal coffee consumption during pregnancy may increase the risk of childhood AL. Because of limited studies, further prospective studies are urgently needed to explore the adverse effect of coffee consumption on childhood AL.

Blood levels of folate at birth and risk of childhood leukemia.

BACKGROUND: A role for folate in cancer etiology has long been suspected because of folate's function as a cofactor in DNA methylation and maintenance of DNA synthesis. Previous case-control studies examining the association between risk of childhood acute lymphoblastic leukemia (ALL) and mothers' self-reported folate intake and supplementation have been inconclusive. MATERIALS AND METHODS: We used a quantitative microbiologic assay to measure newborn folate concentrations in archived dried bloodspots collected at birth from 313 incident ALL cases, 44 incident acute myeloid leukemia (AML) cases, and 405 matched population-based controls. RESULTS: Overall, we found no difference in hemoglobin-normalized newborn folate concentrations (HbFol, nmol/g) between ALL cases and controls (2.76 vs. 2.77, P = 0.97) or between AML cases and controls (2.93 vs. 2.76, P = 0.32). Null results persisted after stratification by both birth period (1982-94, 1995-98, and 1999-2002) to account for the start of folate fortification of grain products in the United States, and by self-reported maternal prepregnancy supplement use. Similarly, no association was observed for major ALL subgroups. CONCLUSIONS: Our results do not support an association between birth folate concentrations and risk of childhood AML or major ALL subgroups. IMPACT: However, they do not rule out a role for folate through exposures after birth or in early stages of fetal development.

Maternal consumption of coffee and tea during pregnancy and risk of childhood ALL: results from an Australian case-control study.

OBJECTIVES: To investigate whether maternal coffee and/or tea consumption during the last 6 months of pregnancy was associated with risk of childhood ALL. METHODS: Data on coffee and tea drinking during pregnancy from 337 case mothers and 697 control mothers were analyzed using unconditional multivariable logistic regression. A meta-analysis of our findings with those of previous studies was also conducted. RESULTS: There was little evidence of an overall association between maternal coffee consumption and risk of ALL: OR 0.89 (95% CI 0.61, 1.30), although there was some suggestion that higher levels of intake might increase the risk in children of non-smoking mothers: OR for 2+ cups/day = 1.44 (95% CI 0.85, 2.42); this was supported by our meta-analysis. Risk was also elevated among cases with chromosomal translocations. The overall OR for maternal tea consumption was 0.82 (95% CI 0.56, 1.18), although the OR for T-cell ALL was 0.21 (95% CI 0.08, 0.51). Among ALL cases with translocations, the ORs for tea consumption tended to be elevated: OR = 1.70 (95% CI 0.79-3.68) for 2+ cups/day. CONCLUSIONS: The observed increased risk associated with coffee and tea consumption may be confined to ALL with translocations. These associations should be explored further in large international consortia.

A case of therapy-related ALL with MLL gene rearrangement following treatment of breast cancer.

ALL with MLL gene rearrangement secondary to chemotherapy has been rarely reported. We report a case of therapy-related ALL (t-ALL) with MLL gene rearrangement in a patient who had undergone treatment for breast cancer. A 60-yr-old woman with breast cancer underwent breast-conserving surgery followed by 6 cycles of adjuvant chemotherapy (cyclophosphamide, epirubicin, and fluorouracil) and radiation therapy (dose, 5,040 cGy to the left breast and a 1,000 cGy boost to the tumor bed). A follow-up examination performed 14 months after the chemotherapy revealed no evidence of breast malignancy. However, the patient's complete blood cell count indicated acute leukemia: white blood cell count, 174.1 x 10(9)/L with 88% blasts; Hb level, 12.5 g/dL; and platelet count, 103.0 x 10(9)/L. Examination of the bone marrow aspirate smear revealed a high percentage of blasts (85.1% of all nucleated cells); the blasts showed a pro-B immunophenotype and were positive for CD19, CD79a, HLA-DR, CD34, and terminal deoxynucleotidyl transferase (TdT). Cytogenetic and FISH analyses revealed t(4;11)(q21;q23) and MLL gene rearrangement, respectively. The patient received induction chemotherapy with cyclophosphamide, vincristine, doxorubicin, and dexamethasone and achieved complete remission. Following consolidation chemotherapy, she underwent allogenic peripheral blood stem cell transplantation and has been clinically stable. To our knowledge, this is the first reported case of t-ALL with MLL gene rearrangement following treatment of breast cancer in Korea.

A Case of Therapy-related ALL with MLL Gene Rearrangement Following Treatment of Breast Cancer / 대한진단검사의학회지

ALL with MLL gene rearrangement secondary to chemotherapy has been rarely reported. We report a case of therapy-related ALL (t-ALL) with MLL gene rearrangement in a patient who had undergone treatment for breast cancer. A 60-yr-old woman with breast cancer underwent breast-conserving surgery followed by 6 cycles of adjuvant chemotherapy (cyclophosphamide, epirubicin, and fluorouracil) and radiation therapy (dose, 5,040 cGy to the left breast and a 1,000 cGy boost to the tumor bed). A follow-up examination performed 14 months after the chemotherapy revealed no evidence of breast malignancy. However, the patient's complete blood cell count indicated acute leukemia: white blood cell count, 174.1x10(9)/L with 88% blasts; Hb level, 12.5 g/dL; and platelet count, 103.0x10(9)/L. Examination of the bone marrow aspirate smear revealed a high percentage of blasts (85.1% of all nucleated cells); the blasts showed a pro-B immunophenotype and were positive for CD19, CD79a, HLA-DR, CD34, and terminal deoxynucleotidyl transferase (TdT). Cytogenetic and FISH analyses revealed t(4;11)(q21;q23) and MLL gene rearrangement, respectively. The patient received induction chemotherapy with cyclophosphamide, vincristine, doxorubicin, and dexamethasone and achieved complete remission. Following consolidation chemotherapy, she underwent allogenic peripheral blood stem cell transplantation and has been clinically stable. To our knowledge, this is the first reported case of t-ALL with MLL gene rearrangement following treatment of breast cancer in Korea.

Periconceptional maternal vitamin supplementation and childhood leukaemia: an uncertainty analysis.

BACKGROUND: Recent studies in childhood cancer suggest that maternal vitamin supplementation may reduce the risk of leukaemia, neuroblastoma and certain types of childhood brain tumours. For example, a previous study found a significantly reduced risk of acute lymphoblastic leukaemia (ALL) but not acute myeloid leukaemia (AML) in children with Down syndrome whose mothers reported any vitamin supplement use prior to knowledge of pregnancy (ALL OR adjusted for confounders 0.51, 95% confidence limits (CL): 0.30, 0.89; AML OR adjusted for confounders 0.92, 95% CL 0.48, 1.76). Recall of exposures, including maternal vitamin supplement use, however, may be difficult and subject to error. Epidemiologists are encouraged to quantitatively adjust for systematic error in study results, but often do not. METHODS: The impact that misclassification of maternal vitamin supplement use may have had on the observed ORs in this study was quantified. Uncertainty analysis was used to calculate ORs adjusted for inaccurate reporting of vitamin supplement use under assumed probability distributions for exposure misclassification parameters. RESULTS: Given our assumptions, adjustment for exposure misclassification yielded ORs that were predominantly more protective for ALL than the crude OR. CONCLUSIONS: Uncertainty analysis can give important insights into the magnitude and direction of error in study results due to exposure misclassification.

Vitamin supplement use among children with Down's syndrome and risk of leukaemia: a Children's Oncology Group (COG) study.

Vitamin supplements have been proposed for children with Down's syndrome (DS) with claims of improving cognitive abilities, or immune or thyroid function. Several studies have shown decreased levels of zinc in this population. Because children with DS have a 50-fold increased risk of developing acute leukaemia during the first 5 years of life, we explored the relation between child vitamin and herbal supplement use and the risk of leukaemia in a case-control study. During the period 1997-2002, we enrolled 158 children with DS aged 0-18 years that were diagnosed with acute lymphoblastic leukaemia (ALL) (n = 97) or acute myeloid leukaemia (AML) (n = 61) at participating Children's Oncology Group institutions. We enrolled 173 DS children without leukaemia (controls), selected from the cases' primary care clinic and frequency-matched on age. Data were collected via telephone interviews with mothers of the index child regarding use of multivitamins, zinc, vitamin C, iron and herbal supplements, including age at first use, frequency and duration. Among controls, 57% reported regular multivitamin use (>/=3 times/week for >/=3 months) compared with 48% of ALL cases and 61% of AML cases. We found no evidence of an association between children's regular multivitamin use and ALL or AML (adjusted odds ratios [OR] = 0.94 [95% CI 0.52, 1.70] and 1.90 [0.73, 4.91] respectively). There was a suggestion of an increased risk for AML associated with regular multivitamin use during the first year of life or for an extended duration (ORs = 2.38 [0.94, 5.76] and 2.59 [1.02, 6.59] respectively). Despite being the largest study of DS-leukaemia, our sample size was small, resulting in imprecise effect estimates. Future research should include larger sample sizes as well as a full assessment of diet including vitamin supplementation to adequately examine the relation between nutritional status and childhood leukaemia.

Hair selenium status in children with leukemia and lymphoma.

Selenium (Se) is a trace element contributing to the structure of antioxidant system that saves cells from reactive oxygen species. Low serum Se levels have been reported in pediatric and adult patients with cancers. On the other hand, hair Se levels, predicting the long-term body Se status, have been reported in only adult patients with cancer. The aim of the study was to investigate the hair Se status in children with newly diagnosed lymphoid malignancies and the relation between malnutrition and Se deficiency. Thirty patients with leukemia (n=17) and lymphoma (n=13), and 25 healthy controls were enrolled to the study. Se was determined with atomic absorption spectrophotometrical method. Hair Se levels of the patients were significantly lower than those of control group [666.96+/-341.46 ng/g vs. 1019.22+/-371.83 ng/g (P<0.001)]. Children with lymphoma had lower Se than the children with acute lymphoblastic leukemia but not statistically significant [547.03+/-283.67 ng/g vs. 758.67+/-361.05 ng/g (P>0.05)]. Malnourished patients (11/30) had lower hair Se levels (483.51+/-235.55 ng/g) than those of the controls (P=0.036), whereas the Se levels of the patients who had no malnutrition (773.17+/-352.92 ng/g) were also lower than those of the controls but not statistically significant (P=0.053). There was no correlation between age, sex, and the hair Se levels. In this study, we found that hair Se levels of the children with leukemia and lymphoma, especially those of malnourished patients, were lower than those of controls. Additional studies are needed to determinate whether low levels of hair Se may play a role in carcinogenesis.

Child and maternal household chemical exposure and the risk of acute leukemia in children with Down's syndrome: a report from the Children's Oncology Group.

Compared with the general pediatric population, children with Down's syndrome have a much higher risk of acute leukemia. This case-control study was designed to explore potential risk factors for acute lymphoblastic leukemia and acute myeloid leukemia in children with Down's syndrome living in the United States or Canada. Mothers of 158 children with Down's syndrome and acute leukemia (97 acute lymphoblastic leukemia, 61 acute myeloid leukemia) diagnosed between January 1997 and October 2002 and mothers of 173 children with Down's syndrome but without leukemia were interviewed by telephone. Positive associations were found between acute lymphoblastic leukemia and maternal exposure to professional pest exterminations (odds ratio = 2.25, 95% confidence interval: 1.13, 4.49), to any pesticide (odds ratio = 2.18, 95% confidence interval: 1.08, 4.39), and to any chemical (odds ratio = 2.72, 95% confidence interval: 1.17, 6.35). Most of the associations with acute myeloid leukemia were nonsignificant, and odds ratios were generally near or below 1.0. This exploratory study suggests that household chemical exposure may play a role in the development of acute lymphoblastic leukemia in children with Down's syndrome.