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

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

The epidemiology, treatment patterns, healthcare utilizations and costs of Acute Myeloid Leukaemia (AML) in Taiwan.

BACKGROUNDS: An increasing incidence of Acute Myeloid Leukaemia (AML) has been reported in several Western countries. However, the epidemiology of AML in Asia is very limited. According to the National Comprehensive Cancer Network (NCCN) guideline of AML, a range of conventional therapy options is available to AML patients. Nevertheless, different treatment strategies may result in diverse healthcare utilization and costs. Understanding the treatment patterns, healthcare utilization and costs of AML would thus be essential for clinicians and policymakers to optimize the treatment strategies of AML. OBJECTIVES: The objective of this study was to investigate the incidence, treatment patterns, healthcare utilization and costs of AML in Taiwan using a nationwide population database. METHODS: We retrospectively identified AML patients diagnosed from 2006 to 2015 from the Taiwan Cancer Registry Database (TCRD) and estimated the epidemiology of AML in Taiwan. The TCRD was linked to National Health Insurance Research Database (NHIRD) to collect the treatment patterns and health care utilization. Patients diagnosed with AML from 2011 to 2015 were further identified to analyze treatment patterns, healthcare utilization and costs. RESULTS: The crude annual incidence of AML increased from 2.78 to 3.21 cases per 100,000 individuals from 2006 to 2015. However, the age-standardized rate (ASRs) of AML slightly declined from 2.47 to 2.41 cases per 100,000 individuals in the same period. Among 2,179 AML patients who received induction therapy (median age: 56 years), most of them (n = 1744; 80.04%) received standard-dose cytarabine (SDAC) regimen. The remaining 162 patients received high dose cytarabine (HDAC) and 273 patients received non-standard dose cytarabine (N-SDAC) regimen as the induction therapy. The median medical costs in our study for patients treated with chemotherapy alone was $42,271 for HDAC, $36,199 for SDAC and $36,250 for N-SDAC. For those who received hematopoietic stem cell transplantation (HSCT) after induction therapy, their median medical costs were $78,876 for HDAC, $78,593 for SDAC and $79,776 for N-SDAC. CONCLUSIONS: This study is the first population-based study conducted in Asia to provide updated and comprehensive information on epidemiology, treatment patterns and healthcare resource utilization and costs of AML.

A novel nutritional index "simplified CONUT" and the disease risk index independently stratify prognosis of elderly patients with acute myeloid leukemia.

Elderly patients aged 65 or older with acute myeloid leukemia (AML) have poor prognosis. The risk stratification based on genetic alteration has been proposed in national comprehensive cancer network (NCCN) guideline but its efficacy was not well verified especially in real world elderly patients. The nutritional status assessment using controlling nutritional status (CONUT) score is a prognostic biomarker in elderly patients with solid tumors but was not examined in elderly AML patients. We performed prospective analysis of genetic alterations of 174 patients aged 65 or older with newly diagnosed AML treated without hematopoietic stem cell transplantation (HSCT) and developed simplified CONUT (sCONUT) score by eliminating total lymphocyte count from the items to adapt AML patients. In this cohort, both the NCCN 2017 risk group and sCONUT score successfully stratified the overall survival (OS) of the elderly patients. A multivariable analysis demonstrated that adverse group in NCCN 2017 and high sCONUT score were independently associated with poor 2-year OS. Both risk stratification based on NCCN 2017 and sCONUT score predict prognosis in the elderly patients with newly diagnosed AML.

Risk of invasive fungal infections in patients with high-risk MDS and AML receiving hypomethylating agents.

Invasive fungal infections (IFI) are a significant source of morbidity and mortality for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Given the heterogeneity of the population receiving hypomethylating agents (HMA), it is difficult for clinicians to accurately assess their patients' risk of infection. Literature on the incidence of IFI following HMA is limited to several studies of azacitidine. The primary objective of this retrospective study was to establish the incidence of IFI in HMA treated AML/MDS patients at a large U.S. comprehensive cancer center. Secondary objectives included comparing incidence of IFI among pre-specified subgroups to identify potential risk factors for IFI. Two hundred three patients with AML, intermediate to very high risk MDS or chronic myelomonocytic leukemia who received at least two cycles of HMA were included. The incidence of IFI, as defined by the European Organization for Research and Treatment of Cancer / Invasive Fungal Infections Cooperative Group criteria, was 9.6%, with 20 IFI diagnosed following HMA (three proven, four probable, 13 possible). Among the proven cases of IFI, molds included Scedosporium and Fusarium spp. Eleven patients who developed IFIs were neutropenic upon initiating HMA. The majority (17/20) of infections occurred during the first four cycles. Given this incidence, mold-active prophylaxis can be considered in patients who are neutropenic at the start of therapy.

Vitamin D status in children with leukemia, its predictors, and association with outcome.

BACKGROUND: Children and adolescents with leukemia are potentially at high risk of vitamin D inadequacy, which may have clinical relevance for skeletal morbidity, infections, and cancer outcome. This study aimed to evaluate vitamin D status at the time of diagnosis to investigate its predictors and association with overall survival in children with leukemia. PROCEDURE: We included all 295 children and adolescents diagnosed with leukemia at our institution between 1990 and 2016 who had available serum sample from the time of diagnosis. We analyzed serum 25-hydroxyvitamin D and parathyroid hormone levels and correlated them with clinical data. RESULTS: The 25-hydroxyvitamin D level was deficient (< 25 nmol/L), insufficient (25-50 nmol/L), sufficient (50-75 nmol/L), and optimal (> 75 nmol/L) in 6.4%, 26.8%, 39.7%, and 27.1% of the children, respectively. Older age and a more recent time of sampling (calendar year) predicted lower 25-hydroxyvitamin D level. In preschool children (age ≤6 years), lower 25-hydroxyvitamin D level was also associated with acute myeloid leukemia, and a 25-hydroxyvitamin D level < 50 nmol/L was associated with inferior overall survival. In school-aged children (age > 6 years), the 25-hydroxyvitamin D level showed significant seasonal variation. CONCLUSION: It remains unclear whether vitamin D supplementation in pediatric leukemia patients will improve outcome.

Pain in patients with newly diagnosed or relapsed acute leukemia.

PURPOSE: Acute leukemia (AL) is associated with substantial morbidity and mortality. We assessed the prevalence and correlates of pain in patients with newly diagnosed or relapsed AL. METHODS: Patients with newly diagnosed or relapsed AL admitted to a comprehensive cancer center completed the Memorial Symptom Assessment Scale (MSAS), which assesses prevalence, severity, and distress associated with pain and other symptoms. Factors associated with severe pain were assessed using logistic regression. Two raters completed chart reviews in duplicate for patients with severe pain (MSAS severity ≥ 3/4) to determine the site of pain. RESULTS: Three hundred eighteen patients were recruited from January 2008 to October 2013: 245 (77.0%) had acute myeloid or acute promyelocytic leukemia (AML/APL) and 73 (23.0%) had acute lymphoblastic leukemia (ALL); 289 (90.9%) were newly diagnosed and 29 (9.1%) had relapsed disease. Pain was reported in 156/318 (49.2%), of whom 55/156 (35.3%) reported severe pain (≥ 3/4). Pain was associated with all psychological symptoms (all p < 0.005) and some physical symptoms. Severe pain was associated with younger age (p = 0.02), worse performance status (p = 0.04), ALL diagnosis (p = 0.04), and time from onset of chemotherapy (p = 0.03), with pain peaking at 4 weeks after chemotherapy initiation. The most common sites of severe pain were oropharynx (22; 40%), head (12; 21.8%), and abdomen (11; 20%). Only 3 patients (0.9%) were referred to the symptom control/palliative care team during the month prior to or following assessment. CONCLUSIONS: Pain is frequent, distressing, and predictable in patients undergoing induction chemotherapy for AL. Further research is needed to assess the efficacy of early supportive care in this population.

Iron overload in patients with myelodysplastic syndromes: An updated overview.

Myelodysplastic syndromes (MDS) encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by a broad clinical spectrum related to ineffective hematopoiesis leading to unilineage or multilineage cytopenias, with a high propensity for transformation to acute myeloid leukemia. Iron overload has been recently identified as one of the important conditions complicating the management of these diverse disorders. The accumulation of iron is mainly related to chronic transfusions; however, evidence suggests a possible role for ineffective erythropoiesis and increased intestinal absorption of iron, related to altered hepcidin and growth differentiation factor-15 levels in the development of hemosiderosis in patients with MDS. In addition to its suggested role in the exacerbation of ineffective erythropoiesis, multiple reports have identified a prognostic implication for the development of iron overload in patients with MDS, with an improvement in overall survival after the initiation of iron chelation therapy. This review includes a detailed discussion of iron overload in patients with MDS whether they are undergoing supportive therapy or curative hematopoietic stem cell transplantation, with a focus on the mechanism, diagnosis, and effect on survival as well as the optimal management of this highly variable complication.

Coffee and green tea consumption and subsequent risk of acute myeloid leukemia and myelodysplastic syndromes in Japan.

Although coffee and green tea are suggested to reduce the risk of some types of cancers, only a few epidemiological studies have investigated their effect on the risk of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Here, we investigated the association of coffee and green tea consumption and the risk of AML and MDS in a large-scale population-based cohort study in Japan. A total of 95,807 Japanese subjects (45,937 men and 49,870 women; age 40-69 years at baseline) were followed to the end of 2012, for an average of 18 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between coffee and green tea consumption at baseline and the risk of AML and MDS were assessed using a Cox proportional hazards model with adjustment for potential confounders. During 1,751.956 person-years, we identified 85 AML cases and 70 MDS cases. Our findings showed no significant association between coffee consumption and the risk of AML, or between green tea consumption and the risk of AML or MDS. In contrast, we observed a decreasing dose-response relationship between coffee consumption and the risk of MDS among men (almost none: reference, 1-4 times/week: HR = 0.83, 95% CI: 0.43-1.62; ≥1cups/day: HR = 0.47, 0.22-0.99, p for trend = 0.049). Stratified analysis by smoking status suggested that the observed relative risk for AML and MDS of coffee drinkers relative to non-coffee drinkers might be due to residual confounding by smoking. These findings deserve further investigation in future studies.

The impact of antimicrobial prophylaxis in morbidity and infections during azacitidine treatment.

The clinical consequences of the infectious events in patients receiving azacitidine are poorly documented. Likewise, the role of primary antimicrobial prophylaxis is unknown. In this retrospective, single-center study, we compare the impact of prophylaxis on the incidence of infection and morbidity in all consecutive higher-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients, during the first 4 azacitidine cycles. Seventy-six patients, corresponding to 283 azacitidine cycles, were studied. There were infectious events in 43% of the patients. Development of infections led to more hospital admissions, increased red blood cells and platelet requirements, and a delay in subsequent cycles. Median overall survival was comparable between patients with or without infections. In the multivariate analysis, a neutrophil count below 0.5 × 109/L (OR 12.5 [2.6-50]) and antimicrobial prophylaxis (OR 0.1 [0.02-04]) were independent factors for the development of infection. We conclude that infectious events have a significant impact in the early clinical course of azacitidine-treated patients by increasing hospital admissions and transfusion requirements. Antimicrobial prophylaxis may prevent infections, leading to a decreased need for supportive care in these patients with poor outcome.

Clinicoepidemiological profiles, clinical practices, and the impact of holistic care interventions on outcomes of pediatric hematolymphoid malignancies - A 7-year audit of the pediatric hematolymphoid disease management group at Tata Memorial Hospital.

INTRODUCTION: The Pediatric Hematolymphoid Disease Management Group (PHL-DMG) at a tertiary cancer care hospital developed extensive patient support programs to improve retention and outcomes while focusing on protocols adapted to meet patient needs. An audit of measures and outcomes was done for a 7-year period from January 2010 to December 2016. MATERIALS AND METHODS: DMG protocols and patient support activities over the study period were documented and audited. Data was retrieved from internal databases and records. Measures taken and their impact were assessed by descriptive analytical tools. Survival outcomes were calculated using Kaplan-Meier method on SPSS v. 24™ software. RESULTS: Holistic patient support measures were undertaken through a charitable foundation entirely under pediatric oncology. Activities included infrastructure growth, socioeconomic support, provision of accommodation, nutrition, education, and multiple blood component donation drives. Patient registrations increased from 502 in 2009 to 874 in 2016, with the steepest rise in acute lymphoblastic leukemia (ALL) - 330 (2009) to 547 (2016). Treatment refusal and abandonment rates decreased from 32% to 3.4% over the same period, and male to female ratio decreased from 2.56 to 2.28:1. Early mortality in acute myeloid leukemia (AML) fell within 2 years from 26.7% in 2009 to 7%. Five-year overall survival (OS) was 69.5% for all patients registered in 2010, whereas disease-specific 5-year OS was ALL 67.1%, AML 49.3%, chronic myeloid leukemia 100%, Hodgkin lymphoma 90.4%, and non-Hodgkin lymphoma 74.2%. CONCLUSIONS: Holistic patient support-specific activities and adapted protocols made a measurable impact on patient outcomes. High survival outcomes of patients have been achieved despite relatively few receiving salvage therapies or stem cell transplant.

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.

An Evaluation of Treatment Patterns and Outcomes in Elderly Patients Newly Diagnosed With Acute Myeloid Leukemia: A Retrospective Analysis of Electronic Medical Records From US Community Oncology Practices.

BACKGROUND: Many elderly patients with acute myeloid leukemia (AML) are considered ineligible for standard intensive induction therapy due to performance status and comorbidities. We analyzed treatment patterns and outcomes among elderly patients newly diagnosed with AML in the US community oncology setting. METHODS: A retrospective observational study was conducted using patient-level data from a network of US community oncology practices provided by Altos Solutions. Patients aged ≥ 60 years, diagnosed with AML between November 2005 and February 2014, with ≥ 1 recorded visit and ≥ 6 months between diagnosis and data cutoff, were included. Only patients who received active treatment or best supportive care (BSC) per National Comprehensive Cancer Network (NCCN) AML Guidelines were analyzed. RESULTS: Of 1139 patients meeting the inclusion criteria, 922 (median age 76 years) received NCCN-recommended treatments: standard induction (n = 5), low-intensity therapy (n = 425), BSC with hydroxyurea (HU) (n = 36), or BSC without HU (n = 455). For the low-intensity therapy cohort, median time from diagnosis to treatment initiation was 17 days; median duration of therapy was 5.1 months. Median overall survival (OS) from diagnosis in the low-intensity, BSC with HU, and BSC without HU groups was 12.3, 7.0, and 49.4 months, respectively. Median time to next therapy/death was 10.1 months in patients receiving low-intensity therapy. A higher proportion of patients receiving low-intensity therapy required transfusion or other supportive care versus those receiving BSC. CONCLUSIONS: As expected, OS in patients receiving low-intensity therapy or BSC with HU is poor for elderly patients with AML. Remarkably, intensive induction strategies are rarely used for older patients in community oncology practice.

Comorbidity, age, and mortality among adults treated intensively for acute myeloid leukemia (AML).

INTRODUCTION: Our goal was to characterize comorbidities among adults receiving intensive therapy for AML, and investigate their association with outcomes. METHODS: We retrospectively analyzed 277 consecutive patients with newly diagnosed AML treated intensively at the Comprehensive Cancer Center of Wake Forest University from 2002 to 2009. Pretreatment comorbidities were identified by ICD-9 codes and chart review. Comorbidity burden (modified Charlson Comorbidity Index [CCI]) and specific conditions were analyzed individually. Outcomes were overall survival (OS), remission, and 30-day mortality. Covariates included age, gender, cytogenetic characteristics, hemoglobin, white cell count, lactate dehydrogenase, body mass index, and insurance type. Cox proportional hazards models were used to evaluate OS; logistic regression was used for remission and 30-day mortality. RESULTS: In this series, 144 patients were ≥ 60 years old (median age 70 years, median survival 8.7 months) and 133 were <60 years (median age 47 years, median survival 23.1 months). Older patients had a higher comorbidity burden (CCI≥1 58% versus 26%, P<0.001). Prevalent comorbid conditions differed by age (diabetes 19.2% versus 7.5%; cardiovascular disease 12.5% versus 4.5%, for older versus younger patients, respectively). The CCI was not independently associated with OS or 30-day mortality in either age group. Among older patients, diabetes was associated with higher 30-day mortality (33.3% vs. 12.0% in diabetic vs. non-diabetic patients, p=0.006). Controlling for age, cytogenetic characteristics and other comorbidities, the presence of diabetes increased the odds of 30-day mortality by 4.9 (CI 1.6-15.2) times. DISCUSSION: Diabetes is adversely associated with 30-day survival in older AML patients receiving intensive therapy.

Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy, and childhood acute leukemia: the ESTELLE study.

PURPOSE: To investigate the role of parental smoking during pre-conception and pregnancy, maternal beverage consumption (alcohol, coffee and tea) during pregnancy and their possible interactions, in the etiology of childhood acute leukemia (CL). METHODS: The ESTELLE study included 747 cases of CL [636 cases of acute lymphoblastic leukemia (ALL) and 100 cases of acute myeloblastic leukemia (AML)] diagnosed in France in 2010-2011 and 1,421 population controls frequency-matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to the mothers. The odds ratios (OR) and their 95 % confidence intervals were estimated using unconditional logistic regression models adjusted for potential confounders. RESULTS: AML, but not ALL, was non-significantly associated with alcohol drinking during pregnancy [OR = 1.3 (0.8-2.0)] with a significant positive dose-response trend (p-trend = 0.02). Pre-conception paternal smoking was significantly associated with ALL [OR = 1.2 (1.1-1.5)] and AML [OR = 1.5 (1.0-2.3)]. CL was not associated with maternal smoking [OR = 1.0 (0.8-1.2)], or maternal coffee [OR = 0.9 (0.8-1.1)] or tea drinking [OR = 0.9 (0.8-1.1)] during pregnancy. However, a high consumption of coffee (>2 cups/day) was significantly associated with ALL [OR = 1.3 (1.0-1.8)]. CONCLUSIONS: The findings constitute additional evidence that maternal alcohol drinking during pregnancy may be involved in AML, and that paternal smoking before pregnancy may be a risk factor for CL. The role of maternal coffee drinking in CL remains unclear and should be investigated further in consortium analyses and in large birth cohort studies with exposure assessment more contemporaneous with the exposure, before the occurrence of the disease.

Maternal supplementation with folic acid and other vitamins and risk of leukemia in offspring: a Childhood Leukemia International Consortium study.

BACKGROUND: Maternal prenatal supplementation with folic acid and other vitamins has been inconsistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Little is known regarding the association with acute myeloid leukemia (AML), a rarer subtype. METHODS: We obtained original data on prenatal use of folic acid and vitamins from 12 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2012), including 6,963 cases of ALL, 585 cases of AML, and 11,635 controls. Logistic regression was used to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for child's age, sex, ethnicity, parental education, and study center. RESULTS: Maternal supplements taken any time before conception or during pregnancy were associated with a reduced risk of childhood ALL; odds ratios were 0.85 (95% CI = 0.78-0.92) for vitamin use and 0.80 (0.71-0.89) for folic acid use. The reduced risk was more pronounced in children whose parents' education was below the highest category. The analyses for AML led to somewhat unstable estimates; ORs were 0.92 (0.75-1.14) and 0.68 (0.48-0.96) for prenatal vitamins and folic acid, respectively. There was no strong evidence that risks of either types of leukemia varied by period of supplementation (preconception, pregnancy, or trimester). CONCLUSIONS: Our results, based on the largest number of childhood leukemia cases to date, suggest that maternal prenatal use of vitamins and folic acid reduces the risk of both ALL and AML and that the observed association with ALL varied by parental education, a surrogate for lifestyle and sociodemographic characteristics.

Cancer incidence among 41,000 offshore oil industry workers.

BACKGROUND: Cancer incidence among Norwegian offshore oil industry workers has been studied in two equally sized cohorts of 28000 workers, in a survey-based cohort study followed 1999-2005 and a register-based cohort study followed 1981-2003. AIMS: To determine the overall cancer incidence in both cohorts merged, with an extended follow-up. METHODS: The merged cohort yielded 41,140 individuals followed for cancer diagnoses 1999-2009. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were computed by gender and by period of first employment using cancer registry data. RESULTS: Among female workers, the total number of cancers was slightly higher than expected (SIR 1.17, 95% CI 1.02-1.34), and excesses of acute myeloid leukaemia (AML) (SIR 5.29, 95% CI 1.72-12), malignant melanoma (SIR 2.13, 95% CI 1.41-3.08) and lung cancer (SIR 1.69, 95% CI 1.03-2.61) were observed. Among male workers, the total number of cancer cases was close to that expected (SIR 1.03, 95% CI 0.99-1.08), but cases of pleural cancer (SIR 2.56, 95% CI 1.58-3.91) and bladder cancer (SIR 1.25, 95% CI 1.05-1.49) were higher than expected. Among male workers first employed before 1986, the numbers of observed cancer cases were higher than expected for most sites, while this was not evident among those employed later. CONCLUSIONS: Further studies with exposure data and confounder control are needed to address whether the observed excesses of pleural cancer and AML can be attributed to offshore work.

Maternal reproductive history, fertility treatments and folic acid supplementation in the risk of childhood acute leukemia: the ESTELLE study.

PURPOSE: To investigate the potential involvement of fertility treatments and other conditions of becoming pregnant (infertility, getting pregnant on birth control, maternal history of fetal loss) and folic acid supplements in the etiology of childhood leukemia (CL). METHODS: The ESTELLE study included 747 cases of CL [636 cases of acute lymphoblastic leukemia (ALL) and 100 of acute myeloblastic leukemia (AML)] diagnosed in France in 2010-2011 and 1,421 population controls frequency-matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to mothers. The odds ratios (OR) and their 95% confidence intervals were estimated using unconditional regression models adjusted for potential confounders. RESULTS: CL was not associated with difficulty in becoming pregnant [OR 0.9 (0.7-1.2)], in vitro fertilisation [OR 0.6 (0.3-1.5)] or the use of any fertility treatment [OR 0.8 (0.5-1.1)] for the index pregnancy. CL was not significantly associated with becoming pregnant on contraception [OR 1.2 (0.8-1.8)], but a positive association was observed for third generation oral contraception [OR 4.3 (1.2-16.2)]; however, the result is based on small numbers. Folic acid supplementation during pregnancy was not associated with CL, but an inverse borderline association was observed for supplementation initiated in the 3 months preceding pregnancy [OR 0.7 (0.5-1.0)]. In addition, maternal histories of stillbirth and miscarriage were associated with ALL [OR 2.6 (1.1-5.9)] and AML [OR 1.8 (1.1-2.8)], respectively. CONCLUSIONS: The findings do not suggest that infertility and fertility treatments are risk factors for CL. They suggest that maternal histories of stillbirth and miscarriage may be more frequent among mothers of CL cases and that folic acid supplementation during preconception may reduce the risk of CL.

Myelodysplastic syndrome and benzene exposure among petroleum workers: an international pooled analysis.

BACKGROUND: Benzene at high concentrations is known to cause acute myeloid leukemia (AML), but its relationship with other lymphohematopoietic (LH) cancers remains uncertain, particularly at low concentrations. In this pooled analysis, we examined the risk of five LH cancers relative to lower levels of benzene exposure in petroleum workers. METHODS: We updated three nested case-control studies from Australia, Canada, and the United Kingdom with new incident LH cancers among petroleum distribution workers through December 31, 2006, and pooled 370 potential case subjects and 1587 matched LH cancer-free control subjects. Quantitative benzene exposure in parts per million (ppm) was blindly reconstructed using historical monitoring data, and exposure certainty was scored as high, medium, or low. Two hematopathologists assigned diagnoses and scored the certainty of diagnosis as high, medium, or low. Dose-response relationships were examined for five LH cancers, including the three most common leukemia cell-types (AML, chronic myeloid leukemia [CML], and chronic lymphoid leukemia [CLL]) and two myeloid tumors (myelodysplastic syndrome [MDS] and myeloproliferative disease [MPD]). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, controlling for age, sex, and time period. RESULTS: Cumulative benzene exposure showed a monotonic dose-response relationship with MDS (highest vs lowest tertile, >2.93 vs ≤0.348 ppm-years, OR = 4.33, 95% CI = 1.31 to 14.3). For peak benezene exposures (>3 ppm), the risk of MDS was increased in high and medium certainty diagnoses (peak exposure vs no peak exposure, OR = 6.32, 95% CI = 1.32 to 30.2) and in workers having the highest exposure certainty (peak exposure vs no peak exposure, OR = 5.74, 95% CI = 1.05 to 31.2). There was little evidence of dose-response relationships for AML, CLL, CML, or MPD. CONCLUSIONS: Relatively low-level exposure to benzene experienced by petroleum distribution workers was associated with an increased risk of MDS, but not AML, suggesting that MDS may be the more relevant health risk for lower exposures.

Survey and analysis of the efficacy and prescription pattern of sorafenib in patients with acute myeloid leukemia.

Sorafenib is a multi-kinase inhibitor with activity against several intracellular kinases which may play a role in the pathogenesis of acute myeloid leukemia (AML). In vitro data and results from early clinical trials suggest that sorafenib might be an effective drug for the treatment of AML. However, clinical data are still sparse, and there are only a few reported cases of monotherapy. The aim of the present research was to collect clinical data on efficacy and safety in a systematic way by conducting a survey on clinical experience with sorafenib. Thirty institutions were asked to document all patients treated with sorafenib diagnosed with AML. Of all 29 evaluable patients, six (21%) responded to sorafenib containing treatment by achieving a complete remission (CR, n = 2) or complete remission with incomplete platelet recovery (CRi, n = 4). In 23 patients receiving sorafenib as monotherapy, the CRi rate amounted to 13% and no CRs were documented. Of the 18 FLT-ITD positive patients with sorafenib monotherapy, two patients achieved a CRi (11%). In five FLT3-ITD negative cases, one CRi was documented (20%). Our results suggest the potential ability of the drug to induce remissions in refractory or relapsed AML even when given as monotherapy.

Has there been progress in the treatment of older patients with acute myeloid leukemia?

The treatment of older patients with acute myeloid leukemia (AML) has become increasingly important as the population ages. Progress, measured by overall survival rates, has improved in younger patients, perhaps due to the use of intensive post-remission therapies, but it is unclear what will enable progress for older AML patients. The older AML patient population is very heterogeneous, and both patient-specific and leukemia-specific factors must be taken into consideration when choosing the therapy that will most benefit each patient. In addition to standard and intensive chemotherapy regimens, a number of alternative therapies for previously untreated older AML patients are currently being investigated. These include gemtuzumab ozogamicin, azacitidine, decitabine, and clofarabine.