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Sample records for leukemia risk electronic

  1. Leukemia

    International Nuclear Information System (INIS)

    Mabuchi, Kiyohiko; Kusumi, Shizuyo

    1992-01-01

    Leukemia is the first malignant disease found among A-bomb survivors. Leukemia registration has greatly contributed to epidemiological and hematological studies on A-bomb radiation-related leukemia and other hematopoietic diseases, consisting of community population and the RERF Life Span Study (LSS) sample (approximately 120,000 persons containing A-bomb survivors). Using the fixed LSS cohort, the prevalence rate of leukemia reached the peak during the years 1950-1954, and thereafter, it has been gradually decreased. However, risk patterns for leukemia are still unsolved: has leukemia risk increased in recent years?; are serial changes in leukemia risk influenced by age at the time of exposure (ATE)?; is there variation between Hiroshima and Nagasaki?; and others. To solve these questions, leukemia data are now under analysis using the revised DS86. Relative risk for leukemia, especially chronic myelogenous leukemia and acute lymphocytic leukemia (ALL), is found to be linearly increased with increasing bone marrow doses. Serial patterns of both excess risk and excess relative risk have revealed that leukemia risk is high at 5-10 years after A-bombing in younger A-bomb survivors ATE. The influence of age ATE on serial changes is noticeable in ALL. Another factor involved in the prevalence of leukemia is background (spontaneously developed leukemia), which is the recent interest because young A-bomb survivors ATE reach the cancer-prone age. (N.K.)

  2. Increased leukemia risk in Chernobyl cleanup workers

    Science.gov (United States)

    A new study found a significantly elevated risk for chronic lymphocytic leukemia among workers who were engaged in recovery and clean-up activities following the Chernobyl power plant accident in 1986.

  3. Leukemia risk following radiotherapy for breast cancer

    International Nuclear Information System (INIS)

    Curtis, R.E.; Boice, J.D. Jr.; Stovall, M.; Flannery, J.T.; Moloney, W.C.

    1989-01-01

    To evaluate further the relationship between high-dose radiotherapy and leukemia incidence, a nested case-control study was conducted in a cohort of 22,753 women who were 18-month survivors of invasive breast cancer diagnosed from 1935 to 1972. Women treated for breast cancer after 1973 were excluded to minimize the possible confounding influence of treatment with chemotherapeutic agents. The cases had histologically confirmed leukemia reported to the Connecticut Tumor Registry (CTR) between 1935 and 1984. A total of 48 cases of leukemia following breast cancer were included in the study. Two controls were individually matched to each leukemia case on the basis of age, calendar year when diagnosed with breast cancer, and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. Local radiation doses to each of the 16 bone marrow components for each patient were reconstructed; the dose averaged over the entire body was 530 rad (5.3 Gy). Based on this dosage and assuming a linear relationship between dose and affect, a relative risk (RR) in excess of 10 would have been expected. However, there was little evidence that radiotherapy increased the overall risk of leukemia (RR = 1.16; 90% confidence interval [CI], 0.6 to 2.1). The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not significantly increased (RR = 1.8; n = 10); nor was the risk for all other forms of leukemia (RR = 1.0; n = 38). There was no indication that risk varied over categories of radiation dose

  4. Risk Groups for Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... cells in the blood at the time of diagnosis. Whether the leukemia cells began from B lymphocytes or T lymphocytes. ... How long it is between the time of diagnosis and when the leukemia comes back. Whether the leukemia comes back in ...

  5. Radiogenic leukemia risk analysis for the Techa River Cohort members

    International Nuclear Information System (INIS)

    Krestinina, L.Y.; Epifanova, S.B.; Akleyev, A.V.; Preston, D.; Davis, F.; Ron, E.

    2008-01-01

    Full text: Members of the Techa River Cohort have been exposed to a long-term external and internal irradiation due to releases of radioactive waste from the Mayak Production Association into the Techa River. Since internal exposure resulted primarily from incorporation of 90 Sr in the bone structure, the bone marrow was the principal target. The maximum dose to the red bone marrow accumulated over 50 years in cohort members reached 2 Gy, and the mean dose was 0.3 Gy. The epidemiological analysis of radiogenic risk of leukemia development was conducted based on the retrospective cohort study approach and regression analysis using the Epicure statistical packet. The extended Techa River Cohort (ETRC) includes about 30 thousand people of the two genders, various ages and different ethnicity (mostly Russians, Tartars and Bashkirs). The catchment area for leukemia mortality and incidence follow-up includes the whole Chelyabinsk and Kurgan Oblasts. The previous analysis of leukemia mortality risk for a 50-year follow-up period pointed out statistically significant dose dependence. The presentation will for the first time describe the results of leukemia incidence risk analyses for the period from 1953 through 2004. Over this 52-year follow-up period 92 leukemia cases (42 in men and 50 in women) were registered among ETRC members resident in the catchment area. Among those 92 cases there were 22 cases attributed to chronic lymphoid leukemia (12 in men and 10 in women). The preliminary analysis of leukemia incidence risk showed a statistically significant linear dependence on dose for total leukemias (p = 0.006), as well as for leukemias with CLL excluded (p < 0.001). The point value of the total leukemia incidence ERR was 2.0/Gy (95% CI: 0.4-15.4) and for leukemia with CLL excluded the ERR was 4.5/Gy (95% CI: 1.1-14.7). More than 57% of leukemia cases (excluding CLL) registered in ETRC members could be related to the radiogenic factor. Analyses of chronic lymphoid

  6. Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  7. Leukemia risk as a consequence of Mayak PA operation

    International Nuclear Information System (INIS)

    Kuznetsova, I.S.; Koshurnikova, N. A.

    2004-01-01

    The purpose of this study is the epidemiological risk assessment of leukemia incidence and mortality in population of Ozyorsk, the closest town to Mayak Production Association as well as in Mayak workers during 1948-2000. Standardized rates of leukemia incidence and mortality in the whole population of Ozyorsk were proved to be significantly higher in comparison with national rates. Relative risk values decrease 10-30% in occupationally non-exposed population ( the rest of the population) compared with estimations on the whole population, however, remaining to be more than one. Standardized incidence rate (SIR) in males was: 1, 33 (95% CI: 1,00-1,75), in females: 1,17 (95% CI: 0,90-1,49), Standardized mortality rate (SMR) in males was 1,34 (95%CI:1,01-1,74), in females 1,24 (95% CI:0,97-1,56). Given more accurate diagnostics in the city compared with national one, there are no grounds to connect the increase in leukemia incidence and mortality in the rest of the population with radiation factor also because now there is no information on dose effect due to living in the vicinity of Mayak Production Association. Standardized leukemia mortality ratio in Mayak workers was 1,91 (95% CI: 1,48-2,43) in males and 2,07 (95% CI:1,31-3,10) in females. Regardless of the better quality of fit in linear-quadratic model, the preference in the analysis is given to linear dependence which allows to avoid underestimation of risk at doses of most interest for radiation protection. The doses were lagged for 2 years. Thus, using linear model with 2-year lag excess relative risk per 1 Gy of external g-exposure was 1.8 (95% CI:0.8-3,6). The study of risk dependence to time since exposure demonstrated that the highest risk of leukemia mortality falls on the period of 2-5 years after exposure (excess relative risk of leukemia mortality in this, period was 11,1 compared to the period of 0-2 years). Excess relative risk for the period of 5-10 years is 7,6, i. e. 1,5 times lower than in the

  8. Leukemia - B-Cell Prolymphocytic Leukemia and Hairy Cell Leukemia

    Science.gov (United States)

    ... Leukemia - B-cell Prolymphocytic Leukemia and Hairy Cell Leukemia Introduction Statistics Risk Factors Symptoms and Signs Diagnosis Stages Treatment Options About Clinical Trials Latest Research ...

  9. A scanning electron microscopic study of 34 cases of acute granulocytic, myelomonocytic, monoblastic and histiocytic leukemia.

    Science.gov (United States)

    Polliack, A; McKenzie, S; Gee, T; Lampen, N; de Harven, E; Clarkson, B D

    1975-09-01

    This report describes the surface architecture of leukemic cells, as seen by scanning electron microscopy in 34 patients with acute nonlymphoblastic leukemia. Six patients with myeloblastic, 4 with promyelocytic, 10 with myelomonocytic, 8 with monocytic, 4 with histiocytic and 2 with undifferentiated leukemia were studied. Under the scanning electron microscope most leukemia histiocytes and monocytes appeared similar and were characterized by the presence of large, well developed broad-based ruffled membranes or prominent raised ridge-like profiles, resembling ithis respect normal monocytes. Most cells from patients with acute promyelocytic or myeloblastic leukemia exhibited narrower ridge-like profiles whereas some showed ruffles or microvilli. Patients with myelomonocytic leukemia showed mixed populations of cells with ridge-like profiles and ruffled membranes whereas cells from two patients with undifferentiated leukemia had smooth surfaces, similar to those encountered in cells from patients with acute lymphoblastic leukemia. It appears that nonlymphoblastic and lymphoblastic leukemia cells (particularly histiocytes and monocytes) can frequently be distinquished on the basis of their surface architecture. The surface features of leukemic histiocytes and monocytes are similar, suggesting that they may belong to the same cell series. The monocytes seem to have characteristic surface features recognizable with the scanning electron microscope and differ from most cells from patients with acute granulocytic leukemia. Although overlap of surface features and misidentification can occur, scanning electron microscopy is a useful adjunct to other modes of microscopy in the study and diagnosis of acute leukemia.

  10. [Effects of birth order, maternal abortion and mode of delivery on childhood acute leukemia risk: a meta-analysis].

    Science.gov (United States)

    Zou, Guobin; Sha, Xia

    2014-03-01

    To evaluate the associations between birth order, maternal abortion and mode of delivery and childhood acute leukemia risk. Multiple electronic databases were searched to identify relevant studies up to March 2013 using the search terms "childhood leukemia", "acute lymphoblastic leukemia", "acute myeloid leukemia","birth order", "abortion", "miscarriage", "cesarean", "birth characteristics" and "prenatal risk factor". Data from cohort and case-control studies were analyzed using the Stata software. Twenty-three studies were included in this meta-analysis according to the selection criteria. No significant associations were identified for birth order and mode of delivery (birth order = 2: OR = 0.97, 95%CI: 0.89-1.05; birth order = 3: OR = 1.00, 95%CI: 0.91-1.11; birth order ≥ 4: OR = 1.02, 95%CI: 0.87-1.20; mode of delivery: OR = 1.05, 95%CI: 0.96-1.15). However, there was a significant association between maternal abortion and childhood acute leukemia risk (spontaneous abortion: OR = 1.21, 95%CI: 1.05-1.41; induced abortion: OR = 1.23, 95%CI: 1.07-1.43). Furthermore, the stratified analysis by disease subtypes showed that spontaneous and induced abortions were significantly associated with the risks of childhood acute myeloid leukemia (OR = 1.71, 95%CI: 1.09-2.70) and acute lymphoblastic leukemia (OR = 1.23, 95%CI: 1.05-1.42), respectively. This meta-analysis revealed that maternal abortion might contribute to the childhood acute leukemia risk.

  11. Maternal and perinatal risk factors for childhood leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Zack, M.; Adami, H.O.; Ericson, A. (Centers for Disease Control, Atlanta, GA (USA))

    1991-07-15

    This report describes an exploratory population-based study of maternal and perinatal risk factors for childhood leukemia in Sweden. The Swedish National Cancer Registry ascertained 411 cases in successive birth cohorts from 1973 through 1984 recorded in the Swedish Medical Birth Registry. Using the latter, we matched five controls without cancer to each case by sex and month and year of birth. Mothers of children with leukemia were more likely to have been exposed to nitrous oxide anesthesia during delivery than mothers of controls (odds ratio (OR) = 1.3; 95% confidence interval (CI) = 1.0, 1.6). Children with leukemia were more likely than controls to have Down's syndrome (OR = 32.5; 95% CI = 7.3, 144.0) or cleft lip or cleft palate (OR = 5.0; 95% CI = 1.0, 24.8); to have had a diagnosis associated with difficult labor but unspecified complications (OR = 4.5; 95% CI = 1.1, 18.2) or with other conditions of the fetus or newborn (OR = 1.5; 95% CI = 1.1, 2.1), specifically, uncomplicated physiological jaundice (OR = 1.9; 95% CI = 1.2, 2.9); or to have received supplemental oxygen (OR = 2.6; 95% CI = 1.3, 1.3, 4.9). Because multiple potential risk factors were analyzed in this study, future studies need to check these findings. The authors did not confirm the previously reported higher risks for childhood leukemia associated with being male, having a high birth weight, or being born to a woman of advanced maternal age.

  12. Neural Correlates of Risk Perception: HIV vs. Leukemia

    Directory of Open Access Journals (Sweden)

    Alexander eBarth

    2013-11-01

    Full Text Available Field studies on HIV risk perception suggest that people may rely on impressions they have about the safety of their partner. Previous studies show that individuals perceived as 'risky' regarding HIV elicit a differential brain response in both earlier (~200 - 350 ms and later (~350 - 700 ms time windows compared to those perceived as safe. This raises the question whether this ERP response is specific to contagious life-threatening diseases or a general mechanism triggered by life-threatening but non-contagious diseases. In the present study, we recorded dense sensor EEG while participants (N = 36 evaluated photographs of unacquainted individuals for either HIV or leukemia risk. The ERP results replicated previous findings revealing earlier and later differential brain responses towards individuals perceived as high risk for HIV. However, there were no significant ERP differences for high vs. low leukemia risk. Rather than reflecting a generic response to disease, the present findings suggest that intuitive judgments of HIV risk are at least in part specific to sexually transmitted diseases.

  13. Acute myeloid leukemia risk by industry and occupation.

    Science.gov (United States)

    Tsai, Rebecca J; Luckhaupt, Sara E; Schumacher, Pam; Cress, Rosemary D; Deapen, Dennis M; Calvert, Geoffrey M

    2014-11-01

    Acute myeloid leukemia (AML) is the most common type of leukemia found in adults. Identifying jobs that pose a risk for AML may be useful for identifying new risk factors. A matched case-control analysis was conducted using California Cancer Registry data from 1988 to 2007. This study included 8999 cases of AML and 24 822 controls. Industries with a statistically significant increased AML risk were construction (matched odds ratio [mOR] = 1.13); crop production (mOR = 1.41); support activities for agriculture and forestry (mOR = 2.05); and animal slaughtering and processing (mOR = 2.09). Among occupations with a statistically significant increased AML risk were miscellaneous agricultural workers (mOR = 1.76); fishers and related fishing workers (mOR = 2.02); nursing, psychiatric and home health aides (mOR = 1.65); and janitors and building cleaners (mOR = 1.54). Further investigation is needed to confirm study findings and to identify specific exposures responsible for the increased risks.

  14. Birth Characteristics and Childhood Leukemia Risk: Correlations With Genetic Markers.

    Science.gov (United States)

    Kennedy, Amy E; Kamdar, Kala Y; Lupo, Philip J; Okcu, Mehmet F; Scheurer, Michael E; Dorak, Mehmet T

    2015-07-01

    Birth characteristics such as birth order, birth weight, birth defects, and Down syndrome showed some of the first risk associations with childhood leukemia. Examinations of correlations between birth characteristics and leukemia risk markers have been limited to birth weight-related genetic polymorphisms. We integrated information on nongenetic and genetic markers by evaluating the relationship of birth characteristics, genetic markers for childhood acute lymphoblastic leukemia (ALL) susceptibility, and ALL risk together. The multiethnic study consisted of cases with childhood ALL (n=161) and healthy controls (n=261). Birth characteristic data were collected through questionnaires, and genotyping was achieved by TaqMan SNP Genotyping Assays. We observed risk associations for birth weight over 4000 g (odds ratios [OR]=1.93; 95% confidence interval [CI], 1.16-3.19), birth length (OR=1.18 per inch; 95% CI, 1.01-1.38), and with gestational age (OR=1.10 per week; 95% CI, 1.00-1.21). Only the HFE tag single-nucleotide polymorphism (SNP) rs9366637 showed an inverse correlation with a birth characteristic, gestational age, with a gene-dosage effect (P=0.005), and in interaction with a transferrin receptor rs3817672 genotype (Pinteraction=0.05). This correlation translated into a strong association for rs9366637 with preterm birth (OR=5.0; 95% CI, 1.19-20.9). Our study provides evidence for the involvement of prenatal events in the development of childhood ALL. The inverse correlation of rs9366637 with gestational age has implications on the design of HFE association studies in birth weight and childhood conditions using full-term newborns as controls.

  15. [Risk factors associated with the development of leukemia in children].

    Science.gov (United States)

    Fajardo-Gutiérrez, A; Garduño-Espinosa, J; Yamamoto-Kimura, L; Hernández-Hernández, D M; Mejía-Aranguré, M; Gómez-Delgado, A; Farfán-Canto, J M; Ortiz-Fernández, A; Martínez-García, M C

    1993-04-01

    Leukemia is the most frequent neoplasia in children; in our country it is the main cause of medical attention in children with cancer. The are different risk factors associated with the development of this kind of cancer. To identify which of the already known factors described in the literature associated with the development of leukemia are most frequent in the pediatric population of Mexico City. A protective case-control study was carried out using prevalent and incident cases. In two third level hospitals of Mexico City, a total of 81 children who had been diagnosed as suffering from different kind of leukemia, confirmed by biopsy of bone marrow, were select and studied. The control were 154 children from two different sources: 77 of them came from the same hospital where the cases received medical care, the selection criteria was not to have any kind of neoplasia; and 77 came from the same community where those diagnosed children cases lived, the selection criteria for this group was that they were healthy children. Both cases and community controls were visited at home and interview to complete precoded questionnaire with the different variables of the study. The information from the hospital controls was obtained during the time they stayed in the hospital. Odds ratio (OR's) for the different associations were calculated, as well as its confidence intervals at 95% (IC) accord to Cornfield and unconditioned logistic regression was carried out to control confounding variables. OR greater than 1 was found in those with familiar cancer background 1.93 (1.2-3.63); the mother being exposed to X-ray during pregnancy 1.89 (0.84-4.22); previous abortions before the child with leukemia was born 2.44 (1-06-5.68); being born from full term birth 2.42 (0.47-16.65); being born with weight greater that 3500 g 2.21 (1.04-4.33); being exposed to fertilizers 4.73 (1.04-24.14) and insecticides 1.93 (1.05-3.56). OR smaller than 1 was found in those who have been in a hospital

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

    Science.gov (United States)

    Metayer, Catherine; Milne, Elizabeth; Dockerty, John D; Clavel, Jacqueline; Pombo-de-Oliveira, Maria S; Wesseling, Catharina; Spector, Logan G; Schüz, Joachim; Petridou, Eleni; Ezzat, Sameera; Armstrong, Bruce K; Rudant, Jérémie; Koifman, Sergio; Kaatsch, Peter; Moschovi, Maria; Rashed, Wafaa M; Selvin, Steve; McCauley, Kathryn; Hung, Rayjean J; Kang, Alice Y; Infante-Rivard, Claire

    2014-11-01

    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. 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. 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). 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.

  17. Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Birgens, Henrik S

    2011-01-01

    Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia...... are at increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid...... cancer, 13 362 developed brain cancer, and 15 967 developed NHL. In nested studies using Cox regression models on individual participant data, we found that, after adult leukemia, the multivariate adjusted hazard ratios were 4.9 (95% confidence interval [CI], 2.8-8.5) for thyroid cancer, 1.9 (95% CI, 1...

  18. Acute unclassified leukemia: A clinicopathologic study with diagnostic implications of electron microscopy.

    Science.gov (United States)

    Youness, E; Trujillo, J M; Ahearn, M J; McCredie, K B; Cork, A

    1980-01-01

    By rigid cytological and cytochemical criteria, the diagnosis of acute and undifferentiated leukemia was established in 22 patients. According to defined criteria, the leukemic cells could not be classified by conventional light microscopic techniques employed in the study of hematopoietic tissue. Cytochemical studies including peroxidase, periodic acid schiff (PAS) and nonspecific esterase (alpha napthyl butyrate-reacting esterase) stains were done on fresh bone marrow samples, and the percentage of positive leukemia cells for each of these stains was determined on 200 cells. In this series of leukemias, cytochemistry at the light microscope level did not contribute to further classification. Subsequent electron microscopic examination of bone marrow samples from these patients confirmed the immaturity and nuclear/cytoplasmic asynchrony of the leukemic cells. Several in vivo neoplastic markers, such as nuclear blebs, increased nuclear bodies, and cytoplasmic fibrillar bundles could be demonstrated in these cells. Fourteen cases from this series exhibited peroxidase-positive developmental granule formation at the ultrastructural level and were reclassified as acute granulocyte leukemia (AGL). One case was reclassified as lymphoma (poor differentiated type), one case was diagnosed as acute monocytic leukemia (AmonoL), and six cases remained in the undifferentiated category (AUL). Clinical and laboratory features, response to treatment, and survival data were evaluated for these patients. This study demonstrated that electron microscopy is useful in the cytological diagnosis of human leukemia.

  19. Biguanides sensitize leukemia cells to ABT-737-induced apoptosis by inhibiting mitochondrial electron transport

    Science.gov (United States)

    Velez, Juliana; Pan, Rongqing; Lee, Jason T.C.; Enciso, Leonardo; Suarez, Marta; Duque, Jorge Eduardo; Jaramillo, Daniel; Lopez, Catalina; Morales, Ludis; Bornmann, William; Konopleva, Marina; Krystal, Gerald; Andreeff, Michael; Samudio, Ismael

    2016-01-01

    Metformin displays antileukemic effects partly due to activation of AMPK and subsequent inhibition of mTOR signaling. Nevertheless, Metformin also inhibits mitochondrial electron transport at complex I in an AMPK-independent manner, Here we report that Metformin and rotenone inhibit mitochondrial electron transport and increase triglyceride levels in leukemia cell lines, suggesting impairment of fatty acid oxidation (FAO). We also report that, like other FAO inhibitors, both agents and the related biguanide, Phenformin, increase sensitivity to apoptosis induction by the bcl-2 inhibitor ABT-737 supporting the notion that electron transport antagonizes activation of the intrinsic apoptosis pathway in leukemia cells. Both biguanides and rotenone induce superoxide generation in leukemia cells, indicating that oxidative damage may sensitize toABT-737 induced apoptosis. In addition, we demonstrate that Metformin sensitizes leukemia cells to the oligomerization of Bak, suggesting that the observed synergy with ABT-737 is mediated, at least in part, by enhanced outer mitochondrial membrane permeabilization. Notably, Phenformin was at least 10-fold more potent than Metformin in abrogating electron transport and increasing sensitivity to ABT-737, suggesting that this agent may be better suited for targeting hematological malignancies. Taken together, our results suggest that inhibition of mitochondrial metabolism by Metformin or Phenformin is associated with increased leukemia cell susceptibility to induction of intrinsic apoptosis, and provide a rationale for clinical studies exploring the efficacy of combining biguanides with the orally bioavailable derivative of ABT-737, Venetoclax. PMID:27283492

  20. Children with low-risk acute lymphoblastic leukemia are at highest risk of second cancers

    DEFF Research Database (Denmark)

    Nielsen, Stine N; Eriksson, Frank; Rosthøj, Susanne

    2017-01-01

    BACKGROUND: The improved survival rates for childhood acute lymphoblastic leukemia (ALL) may be jeopardized by the development of a second cancer, which has been associated with thiopurine therapy. PROCEDURE: We retrospectively analyzed three sequential Nordic Society of Paediatric Haematology......], intermediate vs. standard risk: 0.16, 95% CI: 0.06-0.43, P diagnosis, ALL HeH, or t(12;21)[ETV6/RUNX1] were observed. A subset analysis on the patients with standard...

  1. Non-radiation risk factors for leukemia: A case-control study among chornobyl cleanup workers in Ukraine.

    Science.gov (United States)

    Gudzenko, N; Hatch, M; Bazyka, D; Dyagil, I; Reiss, R F; Brenner, A; Chumak, V; Babkina, N; Zablotska, L B; Mabuchi, K

    2015-10-01

    Occupational and environmental exposure to chemicals such as benzene has been linked to increased risk of leukemia. Cigarette smoking and alcohol consumption have also been found to affect leukemia risk. Previous analyses in a large cohort of Chornobyl clean-up workers in Ukraine found significant radiation-related increased risk for all leukemia types. We investigated the potential for additional effects of occupational and lifestyle factors on leukemia risk in this radiation-exposed cohort. In a case-control study of chronic lymphocytic and other leukemias among Chornobyl cleanup workers, we collected data on a range of non-radiation exposures. We evaluated these and other potential risk factors in analyses adjusting for estimated bone marrow radiation dose. We calculated Odds Ratios and 95% Confidence Intervals in relation to lifestyle factors and occupational hazards. After adjusting for radiation, we found no clear association of leukemia risk with smoking or alcohol but identified a two-fold elevated risk for non-CLL leukemia with occupational exposure to petroleum (OR=2.28; 95% Confidence Interval 1.13, 6.79). Risks were particularly high for myeloid leukemias. No associations with risk factors other than radiation were found for chronic lymphocytic leukemia. These data - the first from a working population in Ukraine - add to evidence from several previous reports of excess leukemia morbidity in groups exposed environmentally or occupationally to petroleum or its products. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2018-02-22

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  3. Electron microscopic study of spontaneous and experimentally induced leukemia in IRC mice

    International Nuclear Information System (INIS)

    Hiraki, S.; Ranadive, K.J.; Dmochowski, L.

    1974-01-01

    Spontaneous, serially transplanted, and experimentally induced leukemias of ICRC mice were studied by electron microscopy in an attempt to detect the presence of virus particles, if any, and to observe the influence of chemical and hormonal treatment on the presence of these virus particles. The first series of experiments included spontaneous, serially transplanted, and radiation-induced leukemia. The paucity of type C virus particles was quite conspicuous in spontaneous leukemia. Serially transplanted and radiation-accelerated leukemic lesions showed the presence of some type C and intracisternal type A particles. Found in two of these leukemic lesions (thymus and lymphosarcoma), in addition to type C virus particles, were budding and some mature type B virus particles, and numerous intracytoplasmic type A particles. ''Viropexis'' of type B virus particles has been observed in the lymphosarcoma and in a leukemic thymus gland. The second series of experiments included leukemia induced in ovariectomized ICRC mice with 20-methylcholanthrene (MCA), pituitary transplants, and ovarian hormones (estradiol and estradiol-progesterone). In ovariectomized ICRC mice, leukemic lesions induced by MCA or pituitary transplants, or by MCA and pituitary transplants, showed type C virus particles and, in most cases, intracisternal type A particles. In leukemia induced in ovariectomized ICRC mice by MCA and estradiol, numerous intracytoplasmic type A particles were observed but no type C virus particles

  4. Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Birgens, Henrik S

    2011-01-01

    .2-3.1) for brain cancer, and 3.3 (95% CI, 2.5-4.4) for NHL. Corresponding hazard ratios after childhood leukemia were 10.4 (95% CI, 0.4-223) for thyroid cancer, 7.2 (95% CI, 2.0-26) for brain cancer, and 6.5 (95% CI, 0.4-110) for NHL. Patients with adult leukemia have excess risk of thyroid cancer, brain cancer......Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia...... are at increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid...

  5. Radiation-Induced Leukemia at Doses Relevant to Radiation Therapy: Modeling Mechanisms and Estimating Risks

    Science.gov (United States)

    Shuryak, Igor; Sachs, Rainer K.; Hlatky, Lynn; Mark P. Little; Hahnfeldt, Philip; Brenner, David J.

    2006-01-01

    Because many cancer patients are diagnosed earlier and live longer than in the past, second cancers induced by radiation therapy have become a clinically significant issue. An earlier biologically based model that was designed to estimate risks of high-dose radiation induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks. Methods: To extend the model to radiation-induced leukemias, we analyzed in addition to cellular initiation, inactivation, and proliferation a repopulation mechanism specific to the hematopoietic system: long-range migration through the blood stream of hematopoietic stem cells (HSCs) from distant locations. Parameters for the model were derived from HSC biologic data in the literature and from leukemia risks among atomic bomb survivors v^ ho were subjected to much lower radiation doses. Results: Proliferating HSCs that migrate from sites distant from the high-dose region include few preleukemic HSCs, thus decreasing the high-dose leukemia risk. The extended model for leukemia provides risk estimates that are consistent with epidemiologic data for leukemia risk associated with radiation therapy over a wide dose range. For example, when applied to an earlier case-control study of 110000 women undergoing radiotherapy for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for leukemia among women who received a large inhomogeneous fractionated external beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11 cases observed). As a corresponding example for brachytherapy, the predicted ERR of 0.80 among women who received an inhomogeneous low

  6. Non-radiation risk factors for leukemia: A case-control study among chornobyl cleanup workers in Ukraine

    International Nuclear Information System (INIS)

    Gudzenko, N.; Hatch, M.; Bazyka, D.; Dyagil, I.; Reiss, R.F.; Brenner, A.; Chumak, V.; Babkina, N.; Zablotska, L.B.; Mabuchi, K.

    2015-01-01

    Background: Occupational and environmental exposure to chemicals such as benzene has been linked to increased risk of leukemia. Cigarette smoking and alcohol consumption have also been found to affect leukemia risk. Previous analyses in a large cohort of Chornobyl clean-up workers in Ukraine found significant radiation-related increased risk for all leukemia types. We investigated the potential for additional effects of occupational and lifestyle factors on leukemia risk in this radiation-exposed cohort. Methods: In a case-control study of chronic lymphocytic and other leukemias among Chornobyl cleanup workers, we collected data on a range of non-radiation exposures. We evaluated these and other potential risk factors in analyses adjusting for estimated bone marrow radiation dose. We calculated Odds Ratios and 95% Confidence Intervals in relation to lifestyle factors and occupational hazards. Results: After adjusting for radiation, we found no clear association of leukemia risk with smoking or alcohol but identified a two-fold elevated risk for non-CLL leukemia with occupational exposure to petroleum (OR=2.28; 95% Confidence Interval 1.13, 6.79). Risks were particularly high for myeloid leukemias. No associations with risk factors other than radiation were found for chronic lymphocytic leukemia. Conclusions: These data – the first from a working population in Ukraine – add to evidence from several previous reports of excess leukemia morbidity in groups exposed environmentally or occupationally to petroleum or its products. - Highlights: • A unique population – a cohort of 110,645 Chernobyl clean-up workers from Ukraine. • Followed 1986–2006 for leukemia, interviewed about non-radiation risk factors. • Petroleum exposure increased risk for non-CLL leukemias, particularly CML. • No risk factor other than radiation was found for CLL.

  7. Non-radiation risk factors for leukemia: A case-control study among chornobyl cleanup workers in Ukraine

    Energy Technology Data Exchange (ETDEWEB)

    Gudzenko, N., E-mail: gudznat@gmail.com [National Research Center for Radiation Medicine, Kyiv (Ukraine); Hatch, M., E-mail: hatchm@mail.nih.gov [Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (United States); Bazyka, D., E-mail: Bazyka@yahoo.com [National Research Center for Radiation Medicine, Kyiv (Ukraine); Dyagil, I., E-mail: leuk@ukr.net [National Research Center for Radiation Medicine, Kyiv (Ukraine); Reiss, R.F., E-mail: rfr1@columbia.edu [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Brenner, A., E-mail: brennera@mail.nih.gov [Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (United States); Chumak, V., E-mail: Chumak.vadim@gmail.com [National Research Center for Radiation Medicine, Kyiv (Ukraine); Babkina, N., E-mail: natalie.babkina@gmail.com [National Research Center for Radiation Medicine, Kyiv (Ukraine); Zablotska, L.B., E-mail: lydia.zablotska@ucsf.edu [Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, San Francisco, CA (United States); Mabuchi, K., E-mail: mabuchik@mail.nih.gov [Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (United States)

    2015-10-15

    Background: Occupational and environmental exposure to chemicals such as benzene has been linked to increased risk of leukemia. Cigarette smoking and alcohol consumption have also been found to affect leukemia risk. Previous analyses in a large cohort of Chornobyl clean-up workers in Ukraine found significant radiation-related increased risk for all leukemia types. We investigated the potential for additional effects of occupational and lifestyle factors on leukemia risk in this radiation-exposed cohort. Methods: In a case-control study of chronic lymphocytic and other leukemias among Chornobyl cleanup workers, we collected data on a range of non-radiation exposures. We evaluated these and other potential risk factors in analyses adjusting for estimated bone marrow radiation dose. We calculated Odds Ratios and 95% Confidence Intervals in relation to lifestyle factors and occupational hazards. Results: After adjusting for radiation, we found no clear association of leukemia risk with smoking or alcohol but identified a two-fold elevated risk for non-CLL leukemia with occupational exposure to petroleum (OR=2.28; 95% Confidence Interval 1.13, 6.79). Risks were particularly high for myeloid leukemias. No associations with risk factors other than radiation were found for chronic lymphocytic leukemia. Conclusions: These data – the first from a working population in Ukraine – add to evidence from several previous reports of excess leukemia morbidity in groups exposed environmentally or occupationally to petroleum or its products. - Highlights: • A unique population – a cohort of 110,645 Chernobyl clean-up workers from Ukraine. • Followed 1986–2006 for leukemia, interviewed about non-radiation risk factors. • Petroleum exposure increased risk for non-CLL leukemias, particularly CML. • No risk factor other than radiation was found for CLL.

  8. Leukemia -- Eosinophilic

    Science.gov (United States)

    ... social workers, and patient advocates. Cancer.Net Guide Leukemia - Eosinophilic Introduction Statistics Risk Factors Symptoms and Signs Diagnosis Stages Treatment Options About Clinical Trials Latest Research ...

  9. Diagnostic x-ray procedures and risk of leukemia, lymphoma, and multiple myeloma

    International Nuclear Information System (INIS)

    Boice, J.D. Jr.; Morin, M.M.; Glass, A.G.; Friedman, G.D.; Stovall, M.; Hoover, R.N.; Fraumeni, J.F. Jr.

    1991-01-01

    Exposure to diagnostic x-rays and the risk of leukemia, non-Hodgkin's lymphoma (NHL), and multiple myeloma were studied within two prepaid health plans. Adult patients with leukemia (n = 565), NHL (n = 318), and multiple myeloma (n = 208) were matched to controls (n = 1390), and over 25,000 x-ray procedures were abstracted from medical records. Dose response was evaluated by assigning each x-ray procedure a score based on estimated bone marrow dose. X-ray exposure was not associated with chronic lymphocytic leukemia, one of the few malignant conditions never linked to radiation (relative risk [RR], 0.66). For all other forms of leukemia combined (n = 358), there was a slight elevation in risk (RR, 1.17) but no evidence of a dose-response relationship when x-ray procedures near the time of diagnosis were excluded. Similarly, patients with NHL were exposed to diagnostic x-ray procedures more often than controls (RR, 1.32), but the RR fell to 0.99 when the exposure to diagnostic x-ray procedures within 2 years of diagnosis was ignored. For multiple myeloma, overall risk was not significantly high (RR, 1.14), but there was consistent evidence of increasing risk with increasing numbers of diagnostic x-ray procedures. These data suggest that persons with leukemia and NHL undergo x-ray procedures frequently just prior to diagnosis for conditions related to the development or natural history of their disease. There was little evidence that diagnostic x-ray procedures were causally associated with leukemia or NHL. The risk for multiple myeloma, however, was increased among those patients who were frequently exposed to x-rays

  10. Risk of leukemia in susceptible children exposed to preconception, in utero, and postnatal radiation

    International Nuclear Information System (INIS)

    Bross, I.D.J.; Natarajan, N.

    1974-01-01

    Further statistical analysis has clarified the hypothesis that there exists a susceptible subgroup of children who are prone to develop leukemia after exposure to low doses of diagnostic radiation which have no effect on normal insusceptible children. The susceptible group does not show marked increase in relative risk when there is no report of exposure. The risk of developing leukemia among the susceptible children with any of the three types of radiation exposure is markedly increased in the appropriate age groups. The data are concordant with a latent period of 4 to 7 years. (auth)

  11. Surface topography of hairy cell leukemia cells compared to other leukemias as seen by scanning electron microscopy.

    Science.gov (United States)

    Polliack, Aaron; Tadmor, Tamar

    2011-06-01

    This short review deals with the ultrastructural surface architecture of hairy cell leukemia (HCL) compared to other leukemic cells, as seen by scanning electron microscopy (SEM). The development of improved techniques for preparing blood cells for SEM in the 1970s readily enabled these features to be visualized more accurately. This review returns us to the earlier history of SEM, when the surface topography of normal and neoplastic cells was visualized and reported for the first time, in an era before the emergence and use of monoclonal antibodies and flow cytometry, now used routinely to define cells by their immunophenotype. Surface microvilli are characteristic for normal and leukemic lymphoid cells, myelo-monocytic cells lack microvilli and show surface ruffles, while leukemic plasma and myeloma cells and megakaryocytes display large surface blebs. HCL cell surfaces are complex and typically 'hybrid' in nature, displaying both lymphoid and monocytic features with florid ruffles of varying sizes interspersed with clumps of short microvilli cytoplasm. The surface features of other leukemic cells and photomicrographs of immuno-SEM labeling of cells employing antibodies and colloidal gold, reported more than 20 years ago, are shown.

  12. Electron microscopy localization and characterization of functionalized composite organic-inorganic SERS nanoparticles on leukemia cells.

    Science.gov (United States)

    Koh, Ai Leen; Shachaf, Catherine M; Elchuri, Sailaja; Nolan, Garry P; Sinclair, Robert

    2008-12-01

    We demonstrate the use of electron microscopy as a powerful characterization tool to identify and locate antibody-conjugated composite organic-inorganic nanoparticle (COINs) surface enhanced Raman scattering (SERS) nanoparticles on cells. U937 leukemia cells labeled with antibody CD54-conjugated COINs were characterized in their native, hydrated state using wet scanning electron microscopy (SEM) and in their dehydrated state using high-resolution SEM. In both cases, the backscattered electron (BSE) detector was used to detect and identify the silver constituents in COINs due to its high sensitivity to atomic number variations within a specimen. The imaging and analytical capabilities in the SEM were further complemented by higher resolution transmission electron microscopy (TEM) images and scanning Auger electron spectroscopy (AES) data to give reliable and high-resolution information about nanoparticles and their binding to cell surface antigens.

  13. Electron microscopy localization and characterization of functionalized composite organic-inorganic SERS nanoparticles on leukemia cells

    International Nuclear Information System (INIS)

    Koh, Ai Leen; Shachaf, Catherine M.; Elchuri, Sailaja; Nolan, Garry P.; Sinclair, Robert

    2008-01-01

    We demonstrate the use of electron microscopy as a powerful characterization tool to identify and locate antibody-conjugated composite organic-inorganic nanoparticle (COINs) surface enhanced Raman scattering (SERS) nanoparticles on cells. U937 leukemia cells labeled with antibody CD54-conjugated COINs were characterized in their native, hydrated state using wet scanning electron microscopy (SEM) and in their dehydrated state using high-resolution SEM. In both cases, the backscattered electron (BSE) detector was used to detect and identify the silver constituents in COINs due to its high sensitivity to atomic number variations within a specimen. The imaging and analytical capabilities in the SEM were further complemented by higher resolution transmission electron microscopy (TEM) images and scanning Auger electron spectroscopy (AES) data to give reliable and high-resolution information about nanoparticles and their binding to cell surface antigens.

  14. Cigarette smoking and the risk of adult leukemia: results from the Three Mile Island cohort study.

    Science.gov (United States)

    Xu, Xiaohui; Talbott, Evelyn O; Zborowski, Jeanne V; Rager, Judith R

    2007-01-01

    Smoking is an unconfirmed risk factor for the development of leukemia. The authors examined the potential link using data from the Three Mile Island cohort for the period 1979-1995. Eligible for analysis were 24,539 individuals aged 14 years or older who were followed up over 16 years from the Three Mile Island cohort. The authors identified all incident leukemia cases through the Pennsylvania Department of Health Cancer Registry. They used the Cox proportional hazards model to evaluate the relationships and observed 42 incident leukemia cases, including 15 acute myeloid leukemia (AML) cases, in the cohort. After controlling for other confounding factors, the authors found current smoking to be associated with an increased risk of adult AML (relative risk = 3.47; 95% confidence interval = 1.002-11.99). The authors also observed a marginally significant linear trend of risk of AML associated with the number of years smoked (p = .06). The results from this study suggested that cigarette smoking was associated with an increased risk of adult AML. Further investigation is required to confirm these findings.

  15. The risk of chronic myeloid leukemia: Can the dose-response curve be U-shaped?

    Czech Academy of Sciences Publication Activity Database

    Radivoyevitch, T.; Kozubek, Stanislav; Sachs, R. K.

    2002-01-01

    Roč. 157, č. 1 (2002), s. 106-109 ISSN 0033-7587 R&D Projects: GA ČR GA202/01/0197; GA ČR GA301/01/0186; GA AV ČR IBS5004010 Keywords : radiation risk * chronic myeloid leukemia * chromosome translocation Subject RIV: BO - Biophysics Impact factor: 2.768, year: 2002

  16. Statistical Analysis of Competing Risks: Overall Survival in a Group of Chronic Myeloid Leukemia Patients

    Czech Academy of Sciences Publication Activity Database

    Fürstová, Jana; Valenta, Zdeněk

    2011-01-01

    Roč. 7, č. 1 (2011), s. 2-10 ISSN 1801-5603 Institutional research plan: CEZ:AV0Z10300504 Keywords : competing risks * chronic myeloid leukemia (CML) * overall survival * cause-specific hazard * cumulative incidence function Subject RIV: IN - Informatics, Computer Science http://www.ejbi.eu/images/2011-1/Furstova_en.pdf

  17. Extremely low-frequency magnetic fields and risk of childhood leukemia

    DEFF Research Database (Denmark)

    Schüz, Joachim; Dasenbrock, Clemens; Ravazzani, Paolo

    2016-01-01

    Exposure to extremely low-frequency magnetic fields (ELF-MF) was evaluated in an International Agency for Research on Cancer (IARC) Monographs as "possibly carcinogenic to humans" in 2001, based on increased childhood leukemia risk observed in epidemiological studies. We conducted a hazard assess...

  18. Occupation, hobbies, and acute leukemia in adults.

    Science.gov (United States)

    Terry, Paul D; Shore, David L; Rauscher, Garth H; Sandler, Dale P

    2005-10-01

    Occupational and industrial exposures have been implicated in the etiology of leukemia, yet uncertainty remains regarding potential high risk occupations. We examined the associations between self-reported occupations and hobbies and acute leukemia risk using data from 811 cases and 637 controls participating in a case-control study in the U.S. and Canada. We found that several occupations may increase the risk of acute leukemia, particularly occupations related to petroleum products, rubber, nuclear energy, munitions, plastics, and electronics manufacturing. Differences were noted according to histological type. Other occupations and hobbies were not clearly associated with risk.

  19. Dietary resveratrol does not delay engraftment, sensitize to vincristine, or inhibit growth of high-risk acute lymphoblastic leukemia cells in NOD/SCID mice

    Science.gov (United States)

    Acute lymphoblastic leukemia (ALL) with translocation t(4;11) is a high-risk leukemia found in 60-85% of infants with ALL and is often refractory to conventional chemotherapeutics after relapse. Although resveratrol is able to kill high-risk leukemia in vitro, this agent has not been evaluated agai...

  20. Tumor suppressors BTG1 and IKZF1 cooperate during mouse leukemia development and increase relapse risk in B-cell precursor acute lymphoblastic leukemia patients.

    Science.gov (United States)

    Scheijen, Blanca; Boer, Judith M; Marke, René; Tijchon, Esther; van Ingen Schenau, Dorette; Waanders, Esmé; van Emst, Liesbeth; van der Meer, Laurens T; Pieters, Rob; Escherich, Gabriele; Horstmann, Martin A; Sonneveld, Edwin; Venn, Nicola; Sutton, Rosemary; Dalla-Pozza, Luciano; Kuiper, Roland P; Hoogerbrugge, Peter M; den Boer, Monique L; van Leeuwen, Frank N

    2017-03-01

    Deletions and mutations affecting lymphoid transcription factor IKZF1 (IKAROS) are associated with an increased relapse risk and poor outcome in B-cell precursor acute lymphoblastic leukemia. However, additional genetic events may either enhance or negate the effects of IKZF1 deletions on prognosis. In a large discovery cohort of 533 childhood B-cell precursor acute lymphoblastic leukemia patients, we observed that single-copy losses of BTG1 were significantly enriched in IKZF1 -deleted B-cell precursor acute lymphoblastic leukemia ( P =0.007). While BTG1 deletions alone had no impact on prognosis, the combined presence of BTG1 and IKZF1 deletions was associated with a significantly lower 5-year event-free survival ( P =0.0003) and a higher 5-year cumulative incidence of relapse ( P =0.005), when compared with IKZF1 -deleted cases without BTG1 aberrations. In contrast, other copy number losses commonly observed in B-cell precursor acute lymphoblastic leukemia, such as CDKN2A/B, PAX5, EBF1 or RB1 , did not affect the outcome of IKZF1 -deleted acute lymphoblastic leukemia patients. To establish whether the combined loss of IKZF1 and BTG1 function cooperate in leukemogenesis, Btg1 -deficient mice were crossed onto an Ikzf1 heterozygous background. We observed that loss of Btg1 increased the tumor incidence of Ikzf1 +/- mice in a dose-dependent manner. Moreover, murine B cells deficient for Btg1 and Ikzf1 +/- displayed increased resistance to glucocorticoids, but not to other chemotherapeutic drugs. Together, our results identify BTG1 as a tumor suppressor in leukemia that, when deleted, strongly enhances the risk of relapse in IKZF1 -deleted B-cell precursor acute lymphoblastic leukemia, and augments the glucocorticoid resistance phenotype mediated by the loss of IKZF1 function. Copyright© Ferrata Storti Foundation.

  1. Dynamical modeling approach to risk assessment for radiogenic leukemia among astronauts engaged in interplanetary space missions.

    Science.gov (United States)

    Smirnova, Olga A; Cucinotta, Francis A

    2018-02-01

    A recently developed biologically motivated dynamical model of the assessment of the excess relative risk (ERR) for radiogenic leukemia among acutely/continuously irradiated humans (Smirnova, 2015, 2017) is applied to estimate the ERR for radiogenic leukemia among astronauts engaged in long-term interplanetary space missions. Numerous scenarios of space radiation exposure during space missions are used in the modeling studies. The dependence of the ERR for leukemia among astronauts on several mission parameters including the dose equivalent rates of galactic cosmic rays (GCR) and large solar particle events (SPEs), the number of large SPEs, the time interval between SPEs, mission duration, the degree of astronaut's additional shielding during SPEs, the degree of their additional 12-hour's daily shielding, as well as the total mission dose equivalent, is examined. The results of the estimation of ERR for radiogenic leukemia among astronauts, which are obtained in the framework of the developed dynamical model for various scenarios of space radiation exposure, are compared with the corresponding results, computed by the commonly used linear model. It is revealed that the developed dynamical model along with the linear model can be applied to estimate ERR for radiogenic leukemia among astronauts engaged in long-term interplanetary space missions in the range of applicability of the latter. In turn, the developed dynamical model is capable of predicting the ERR for leukemia among astronauts for the irradiation regimes beyond the applicability range of the linear model in emergency cases. As a supplement to the estimations of cancer incidence and death (REIC and REID) (Cucinotta et al., 2013, 2017), the developed dynamical model for the assessment of the ERR for leukemia can be employed on the pre-mission design phase for, e.g., the optimization of the regimes of astronaut's additional shielding in the course of interplanetary space missions. The developed model can

  2. A methodological frame for assessing benzene induced leukemia risk mitigation due to policy measures

    International Nuclear Information System (INIS)

    Karakitsios, Spyros P.; Sarigiannis, Dimosthenis A.; Gotti, Alberto; Kassomenos, Pavlos A.; Pilidis, Georgios A.

    2013-01-01

    The study relies on the development of a methodology for assessing the determinants that comprise the overall leukemia risk due to benzene exposure and how these are affected by outdoor and indoor air quality regulation. An integrated modeling environment was constructed comprising traffic emissions, dispersion models, human exposure models and a coupled internal dose/biology-based dose–response risk assessment model, in order to assess the benzene imposed leukemia risk, as much as the impact of traffic fleet renewal and smoking banning to these levels. Regarding traffic fleet renewal, several “what if” scenarios were tested. The detailed full-chain methodology was applied in a South-Eastern European urban setting in Greece and a limited version of the methodology in Helsinki. Non-smoking population runs an average risk equal to 4.1 · 10 −5 compared to 23.4 · 10 −5 for smokers. The estimated lifetime risk for the examined occupational groups was higher than the one estimated for the general public by 10–20%. Active smoking constitutes a dominant parameter for benzene-attributable leukemia risk, much stronger than any related activity, occupational or not. From the assessment of mitigation policies it was found that the associated leukemia risk in the optimum traffic fleet scenario could be reduced by up to 85% for non-smokers and up to 8% for smokers. On the contrary, smoking banning provided smaller gains for (7% for non-smokers, 1% for smokers), while for Helsinki, smoking policies were found to be more efficient than traffic fleet renewal. The methodology proposed above provides a general framework for assessing aggregated exposure and the consequent leukemia risk from benzene (incorporating mechanistic data), capturing exposure and internal dosimetry dynamics, translating changes in exposure determinants to actual changes in population risk, providing a valuable tool for risk management evaluation and consequently to policy support. - Highlights

  3. A methodological frame for assessing benzene induced leukemia risk mitigation due to policy measures

    Energy Technology Data Exchange (ETDEWEB)

    Karakitsios, Spyros P. [Aristotle University of Thessaloniki, Department of Chemical Engineering, 54124 Thessaloniki (Greece); Sarigiannis, Dimosthenis A., E-mail: denis@eng.auth.gr [Aristotle University of Thessaloniki, Department of Chemical Engineering, 54124 Thessaloniki (Greece); Centre for Research and Technology Hellas (CE.R.T.H.), 57001, Thessaloniki (Greece); Gotti, Alberto [Centre for Research and Technology Hellas (CE.R.T.H.), 57001, Thessaloniki (Greece); Kassomenos, Pavlos A. [University of Ioannina, Department of Physics, Laboratory of Meteorology, GR-45110 Ioannina (Greece); Pilidis, Georgios A. [University of Ioannina, Department of Biological Appl. and Technologies, GR-45110 Ioannina (Greece)

    2013-01-15

    The study relies on the development of a methodology for assessing the determinants that comprise the overall leukemia risk due to benzene exposure and how these are affected by outdoor and indoor air quality regulation. An integrated modeling environment was constructed comprising traffic emissions, dispersion models, human exposure models and a coupled internal dose/biology-based dose–response risk assessment model, in order to assess the benzene imposed leukemia risk, as much as the impact of traffic fleet renewal and smoking banning to these levels. Regarding traffic fleet renewal, several “what if” scenarios were tested. The detailed full-chain methodology was applied in a South-Eastern European urban setting in Greece and a limited version of the methodology in Helsinki. Non-smoking population runs an average risk equal to 4.1 · 10{sup −5} compared to 23.4 · 10{sup −5} for smokers. The estimated lifetime risk for the examined occupational groups was higher than the one estimated for the general public by 10–20%. Active smoking constitutes a dominant parameter for benzene-attributable leukemia risk, much stronger than any related activity, occupational or not. From the assessment of mitigation policies it was found that the associated leukemia risk in the optimum traffic fleet scenario could be reduced by up to 85% for non-smokers and up to 8% for smokers. On the contrary, smoking banning provided smaller gains for (7% for non-smokers, 1% for smokers), while for Helsinki, smoking policies were found to be more efficient than traffic fleet renewal. The methodology proposed above provides a general framework for assessing aggregated exposure and the consequent leukemia risk from benzene (incorporating mechanistic data), capturing exposure and internal dosimetry dynamics, translating changes in exposure determinants to actual changes in population risk, providing a valuable tool for risk management evaluation and consequently to policy support

  4. Occupation and leukemia in Nordic countries

    DEFF Research Database (Denmark)

    Talibov, Madar; Kautiainen, Susanna; Martinsen, Jan Ivar

    2012-01-01

    We studied occupational variation of the risk of acute myeloid leukemia, chronic lymphocytic leukemia, and other leukemia in Nordic countries.......We studied occupational variation of the risk of acute myeloid leukemia, chronic lymphocytic leukemia, and other leukemia in Nordic countries....

  5. Childhood Leukemia

    Science.gov (United States)

    ... acute types. Symptoms include Infections Fever Loss of appetite Tiredness Easy bruising or bleeding Swollen lymph nodes Night sweats Shortness of breath Pain in the bones or joints Risk factors for childhood leukemia include having a brother ...

  6. How breast cancer chemotherapy increases the risk of leukemia: Thoughts about a case of diffuse large B-cell lymphoma and leukemia after breast cancer chemotherapy.

    Science.gov (United States)

    Zhang, Bin; Zhang, Xia; Li, Minghuan; Kong, Li; Deng, Xiaoqin; Yu, Jinming

    2016-01-01

    The latest studies suggest that prophylactic chemotherapy or adjuvant chemotherapy for early stage breast cancer may increase the leukemia risk in patients. For patients with a low risk for breast cancer recurrence, physicians who make the choice for adjuvant therapy should consider the risk of its long-term side effects. Is the occurrence of lymphatic system cancer and leukemia after breast cancer treatment associated with chemotherapy? Can these types of leukemia be classified as therapy-related leukaemias? We believe that there may be correlations between any diseases, butwe cannot rush to conclusions or dismiss a correlation because we understand little about the diseases themselves.In this paper, we present a case of secondary diffuse large B-cell lymphoma and leukemia in patients after breast cancer chemotherapy, it is undeniable that this is a special event. For two distinct tumouroccurrences at different times, we cannot give a clear explanation because of thechanges in the genes that might link them together and we hope to attract the attention of other clinicians.

  7. Chronic lymphocytic leukemia and infection risk in the era of targeted therapies: Linking mechanisms with infections.

    Science.gov (United States)

    Hilal, Talal; Gea Banacloche, Juan C; Leis, Jose F

    2018-03-16

    Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the world. Patient with CLL are at particular risk for infections due to inherent disease-related immune dysfunction in addition to the effect of certain systemic therapies on the immune system. The advent of B-cell receptor (BCR) inhibitors such as ibrutinib and idelalisib has led to a practice change that utilizes these targeted agents in the treatment of CLL, either in place of chemoimmunotherapy (CIT) or in later line settings. In this paper, we review the pathophysiology of immune dysfunction in CLL, the spectrum of immunodeficiency with the various therapeutic agents along with prevention strategies with a focus on targeted therapies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Risk of leukemia among survivors of testicular cancer: a population-based study of 42,722 patients

    DEFF Research Database (Denmark)

    Howard, R.; Gilbert, E.; Lynch, C.F.

    2008-01-01

    PURPOSE: The aim of this study is to quantify excess absolute risk (EAR) and excess relative risk (ERR) of secondary leukemia among a large population-based group of testicular cancer survivors. METHODS: We identified 42,722 1-year survivors of testicular cancer within 14 population-based cancer...... registries in Europe and North America (1943-2002). Poisson regression analysis was used to model EAR (per 100,000 person-years [PY]) and ERR of secondary leukemia. Cumulative risks were calculated using a competing risk model. RESULTS: Secondary leukemia developed in 89 patients (EAR = 10.8 per 100,000 PY......, 95% confidence interval [CI] = 7.6-14.6; ERR = 1.6, 95%CI = 1.0-2.2). Statistically significantly elevated risks were observed for acute myeloid leukemia (AML) (EAR = 7.2, 95%CI = 4.7-10.2) and acute lymphoblastic leukemia (EAR = 1.3, 95%CI = 0.4-2.8). In multivariate analyses, AML risk was higher...

  9. Association between MTHFR polymorphisms and acute myeloid leukemia risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yu-Tao Qin

    Full Text Available Previous observational studies investigating the association between methylenetetrahydrofolate reductase (MTHFR polymorphisms and acute myeloid leukemia risk (AML have yielded inconsistent results. The aim of this study is to derive a more precise estimation of the association between MTHFR (C677T and A1298C polymorphisms and acute myeloid leukemia risk. PubMed and Embase databases were systematically searched to identify relevant studies from their inception to August 2013. Odds ratios (ORs with 95% confidence intervals (CIs were the metric of choice. Thirteen studies were selected for C677T polymorphism (1838 cases and 5318 controls and 9 studies (1335 patients and 4295 controls for A1298C polymorphism. Overall, pooled results showed that C677T polymorphism was not significant associated with AML risk(OR, 0.98-1.04; 95% CI, 0.86-0.92 to 1.09-1.25. Similar results were observed for the A1298C polymorphism and in subgroup analysis. All comparisons revealed no substantial heterogeneity nor did we detect evidence of publication bias. In summary, this meta-analysis provides evidence that MTHFR polymorphisms were not associated with AML risk. Further investigations are needed to offer better insight into the role of these polymorphisms in AML carcinogenesis.

  10. Exposure to benzene at work and the risk of leukemia: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Pukkala Eero

    2010-06-01

    Full Text Available Abstract Background A substantial number of epidemiologic studies have provided estimates of the relation between exposure to benzene at work and the risk of leukemia, but the results have been heterogeneous. To bridge this gap in knowledge, we synthesized the existing epidemiologic evidence on the relation between occupational exposure to benzene and the risk of leukemia, including all types combined and the four main subgroups acute myeloid leukemia (AML, acute lymphocytic leukemia (ALL, chronic lymphocytic leukemia (CLL, and chronic myeloid leukemia (CML. Methods A systematic literature review was carried out using two databases 'Medline' and 'Embase' from 1950 through to July 2009. We selected articles which provided information that can be used to estimate the relation between benzene exposure and cancer risk (effect size. Results In total 15 studies were identified in the search, providing 16 effect estimates for the main analysis. The summary effect size for any leukemia from the fixed-effects model was 1.40 (95% CI, 1.23-1.57, but the study-specific estimates were strongly heterogeneous (I2 = 56.5%, Q stat = 34.47, p = 0.003. The random-effects model yielded a summary- effect size estimate of 1.72 (95% CI, 1.37-2.17. Effect estimates from 9 studies were based on cumulative exposures. In these studies the risk of leukemia increased with a dose-response pattern with a summary-effect estimate of 1.64 (95% CI, 1.13-2.39 for low ( 100 ppm-years. In a meta-regression, the trend was statistically significant (P = 0.015. Use of cumulative exposure eliminated heterogeneity. The risk of AML also increased from low (1.94, 95% CI, 0.95-3.95, medium (2.32, 95% CI, 0.91-5.94 to high exposure category (3.20, 95% CI, 1.09-9.45, but the trend was not statistically significant. Conclusions Our study provides consistent evidence that exposure to benzene at work increases the risk of leukemia with a dose-response pattern. There was some evidence of an

  11. Potential impacts of radon, terrestrial gamma and cosmic rays on childhood leukemia in France: a quantitative risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Laurent, Olivier [French Institute for Radiological Protection and Nuclear Safety, Radiobiology and Epidemiology Department, IRSN, PRP-HOM, SRBE, LEPID, Fontenay aux Roses (France); University of California, Irvine, Department of Population Health and Disease Prevention, Irvine, CA (United States); Ancelet, Sophie; Laurier, Dominique [French Institute for Radiological Protection and Nuclear Safety, Radiobiology and Epidemiology Department, IRSN, PRP-HOM, SRBE, LEPID, Fontenay aux Roses (France); Richardson, David B. [University of North Carolina at Chapel Hill, Department of Epidemiology, School of Public Health, Chapel Hill, NC (United States); Hemon, Denis; Demoury, Claire; Clavel, Jacqueline [Inserm, CESP Center for Research in Epidemiology and Population Health, U1018, Environmental Epidemiology of Cancer Team, Villejuif (France); Paris-Sud University, UMRS 1018, Villejuif (France); Ielsch, Geraldine [French Institute for Radiological Protection and Nuclear Safety, Assessment Unit for Risks Related to Natural Radioactivity, IRSN, PRP-DGE, SEDRAN, BRN, Fontenay aux Roses (France)

    2013-05-15

    Previous epidemiological studies and quantitative risk assessments (QRA) have suggested that natural background radiation may be a cause of childhood leukemia. The present work uses a QRA approach to predict the excess risk of childhood leukemia in France related to three components of natural radiation: radon, cosmic rays and terrestrial gamma rays, using excess relative and absolute risk models proposed by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). Both models were developed from the Life Span Study (LSS) of Japanese A-bomb survivors. Previous risk assessments were extended by considering uncertainties in radiation-related leukemia risk model parameters as part of this process, within a Bayesian framework. Estimated red bone marrow doses cumulated during childhood by the average French child due to radon, terrestrial gamma and cosmic rays are 4.4, 7.5 and 4.3 mSv, respectively. The excess fractions of cases (expressed as percentages) associated with these sources of natural radiation are 20 % [95 % credible interval (CI) 0-68 %] and 4 % (95 % CI 0-11 %) under the excess relative and excess absolute risk models, respectively. The large CIs, as well as the different point estimates obtained under these two models, highlight the uncertainties in predictions of radiation-related childhood leukemia risks. These results are only valid provided that models developed from the LSS can be transferred to the population of French children and to chronic natural radiation exposures, and must be considered in view of the currently limited knowledge concerning other potential risk factors for childhood leukemia. Last, they emphasize the need for further epidemiological investigations of the effects of natural radiation on childhood leukemia to reduce uncertainties and help refine radiation protection standards. (orig.)

  12. Potential impacts of radon, terrestrial gamma and cosmic rays on childhood leukemia in France: a quantitative risk assessment

    International Nuclear Information System (INIS)

    Laurent, Olivier; Ancelet, Sophie; Laurier, Dominique; Richardson, David B.; Hemon, Denis; Demoury, Claire; Clavel, Jacqueline; Ielsch, Geraldine

    2013-01-01

    Previous epidemiological studies and quantitative risk assessments (QRA) have suggested that natural background radiation may be a cause of childhood leukemia. The present work uses a QRA approach to predict the excess risk of childhood leukemia in France related to three components of natural radiation: radon, cosmic rays and terrestrial gamma rays, using excess relative and absolute risk models proposed by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). Both models were developed from the Life Span Study (LSS) of Japanese A-bomb survivors. Previous risk assessments were extended by considering uncertainties in radiation-related leukemia risk model parameters as part of this process, within a Bayesian framework. Estimated red bone marrow doses cumulated during childhood by the average French child due to radon, terrestrial gamma and cosmic rays are 4.4, 7.5 and 4.3 mSv, respectively. The excess fractions of cases (expressed as percentages) associated with these sources of natural radiation are 20 % [95 % credible interval (CI) 0-68 %] and 4 % (95 % CI 0-11 %) under the excess relative and excess absolute risk models, respectively. The large CIs, as well as the different point estimates obtained under these two models, highlight the uncertainties in predictions of radiation-related childhood leukemia risks. These results are only valid provided that models developed from the LSS can be transferred to the population of French children and to chronic natural radiation exposures, and must be considered in view of the currently limited knowledge concerning other potential risk factors for childhood leukemia. Last, they emphasize the need for further epidemiological investigations of the effects of natural radiation on childhood leukemia to reduce uncertainties and help refine radiation protection standards. (orig.)

  13. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

    OpenAIRE

    Berndt, S.I.; Skibola, C.F.; Joseph, V.; Camp, N.J.; Nieters, A.; Wang, Z.; Cozen, W.; Monnereau, A.; Wang, S.S.; Kelly, R.S.; Lan, Q.; Teras, L.R.; Chatterjee, N.; Chung, C.C.; Yeager, M.

    2013-01-01

    Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10...

  14. Xenotropic murine leukemia virus-related virus does not pose a risk to blood recipient safety.

    Science.gov (United States)

    Dodd, Roger Y; Hackett, John; Linnen, Jeffrey M; Dorsey, Kerri; Wu, Yanyun; Zou, Shimian; Qiu, Xiaoxing; Swanson, Priscilla; Schochetman, Gerald; Gao, Kui; Carrick, James M; Krysztof, David E; Stramer, Susan L

    2012-02-01

    When xenotropic murine leukemia virus-related virus (XMRV) was first reported in association with chronic fatigue syndrome, it was suggested that it might offer a risk to blood safety. Thus, the prevalence of the virus among blood donors and, if present, its transmissibility by transfusion need to be defined. Two populations of routine blood donor samples (1435 and 13,399) were obtained for prevalence evaluations; samples from a linked donor-recipient repository were also evaluated. Samples were tested for the presence of antibodies to XMRV-related recombinant antigens and/or for XMRV RNA, using validated, high-throughput systems. The presence of antibodies to XMRV could not be confirmed among a total of 17,249 blood donors or recipients (0%; 95% confidence interval [CI], 0%-0.017%); 1763 tested samples were nonreactive for XMRV RNA (0%; 95% CI, 0%-0.17%). Evidence of infection was absent from 109 recipients and 830 evaluable blood samples tested after transfusion of a total of 3741 blood components. XMRV and related murine leukemia virus (MLV) markers are not present among a large population of blood donors and evidence of transfusion transmission could not be detected. Thus, these viruses do not currently pose a threat to blood recipient safety and further actions relating to XMRV and MLV are not justified. © 2012 American Association of Blood Banks.

  15. Mitochondrial DNA copy number and chronic lymphocytic leukemia/small lymphocytic lymphoma risk in two prospective studies

    NARCIS (Netherlands)

    Kim, Christopher; Bassig, Bryan A; Seow, Wei Jie; Hu, Wei; Purdue, Mark P; Huang, Wen-Yi; Liu, Chin-San; Cheng, Wen-Ling; Männistö, Satu; Vermeulen, Roel; Weinstein, Stephanie J; Lim, Unhee; Hosgood, H Dean; Bonner, Matthew R; Caporaso, Neil E; Albanes, Demetrius; Lan, Qing; Rothman, Nathaniel

    BACKGROUND: Mitochondrial DNA copy number (mtDNA CN) may be modified by mitochondria in response to oxidative stress. Previously, mtDNA CN was associated with non-Hodgkin lymphoma (NHL) risk, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We conducted a replication

  16. Smoking and subsequent risk of leukemia in Japan: The Japan Public Health Center-based Prospective Study.

    Science.gov (United States)

    Ugai, Tomotaka; Matsuo, Keitaro; Sawada, Norie; Iwasaki, Motoki; Yamaji, Taiki; Shimazu, Taichi; Sasazuki, Shizuka; Inoue, Manami; Tsugane, Shoichiro

    2017-07-01

    Cigarette smoking has been reported to be associated with an increased risk of leukemia. Most epidemiological evidence on the association between cigarette smoking and leukemia risk is from studies conducted in Western populations, however, and evidence from Asian populations is scarce. We conducted a large-scale population-based cohort study of 96,992 Japanese subjects (46,493 men and 50,499 women; age 40-69 years at baseline) with an average 18.3 years of follow-up, during which we identified 90 cases of acute myeloid leukemia (AML), 19 of acute lymphoblastic leukemia (ALL), and 28 of chronic myeloid leukemia (CML). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a Cox regression model adjusted for potential confounders. When we adjusted for age, sex, and study area, our findings showed no significant association or increasing dose-response relationship between risk of AML and cigarette smoking overall. However, after further adjustment for body mass index and occupation, current smokers with more than 30 pack-years of cigarette smoking had a significantly increased risk of AML compared to never smokers among men (HR 2.21; 95% CI, 1.01-4.83). This increased risk was not clear among women. Our results suggest that cigarette smoking increases the risk of AML in Japanese men. The associations of smoking with AML among women, and with CML and ALL among men and women, should be assessed in future studies. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  17. Smoking and subsequent risk of leukemia in Japan: The Japan Public Health Center-based Prospective Study

    Directory of Open Access Journals (Sweden)

    Tomotaka Ugai

    2017-07-01

    Full Text Available Background: Cigarette smoking has been reported to be associated with an increased risk of leukemia. Most epidemiological evidence on the association between cigarette smoking and leukemia risk is from studies conducted in Western populations, however, and evidence from Asian populations is scarce. Methods: We conducted a large-scale population-based cohort study of 96,992 Japanese subjects (46,493 men and 50,499 women; age 40–69 years at baseline with an average 18.3 years of follow-up, during which we identified 90 cases of acute myeloid leukemia (AML, 19 of acute lymphoblastic leukemia (ALL, and 28 of chronic myeloid leukemia (CML. Hazard ratios (HRs and 95% confidence intervals (CIs were estimated using a Cox regression model adjusted for potential confounders. Results: When we adjusted for age, sex, and study area, our findings showed no significant association or increasing dose–response relationship between risk of AML and cigarette smoking overall. However, after further adjustment for body mass index and occupation, current smokers with more than 30 pack-years of cigarette smoking had a significantly increased risk of AML compared to never smokers among men (HR 2.21; 95% CI, 1.01–4.83. This increased risk was not clear among women. Conclusions: Our results suggest that cigarette smoking increases the risk of AML in Japanese men. The associations of smoking with AML among women, and with CML and ALL among men and women, should be assessed in future studies.

  18. How Is Chronic Myeloid Leukemia Diagnosed?

    Science.gov (United States)

    ... Myeloid Leukemia? More In Chronic Myeloid Leukemia About Chronic Myeloid Leukemia Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To Top Imagine a world ...

  19. Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

    Science.gov (United States)

    Cancela, Camila Silva Peres; Murao, Mitiko; Viana, Marcos Borato; de Oliveira, Benigna Maria

    2012-01-01

    Background Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. Methods This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. Results The estimated probabilities of overall survival and event free survival at 5 years were 69.5% (± 3.6%) and 58.8% (± 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis ≥ 50 x 109/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count 50 x 109/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia. PMID:23323068

  20. Hierarchy in gene expression is predictive of risk, progression, and outcome in adult acute myeloid leukemia

    Science.gov (United States)

    Tripathi, Shubham; Deem, Michael W.

    2015-02-01

    Cancer progresses with a change in the structure of the gene network in normal cells. We define a measure of organizational hierarchy in gene networks of affected cells in adult acute myeloid leukemia (AML) patients. With a retrospective cohort analysis based on the gene expression profiles of 116 AML patients, we find that the likelihood of future cancer relapse and the level of clinical risk are directly correlated with the level of organization in the cancer related gene network. We also explore the variation of the level of organization in the gene network with cancer progression. We find that this variation is non-monotonic, which implies the fitness landscape in the evolution of AML cancer cells is non-trivial. We further find that the hierarchy in gene expression at the time of diagnosis may be a useful biomarker in AML prognosis.

  1. Hierarchy in gene expression is predictive of risk, progression, and outcome in adult acute myeloid leukemia

    International Nuclear Information System (INIS)

    Tripathi, Shubham; Deem, Michael W

    2015-01-01

    Cancer progresses with a change in the structure of the gene network in normal cells. We define a measure of organizational hierarchy in gene networks of affected cells in adult acute myeloid leukemia (AML) patients. With a retrospective cohort analysis based on the gene expression profiles of 116 AML patients, we find that the likelihood of future cancer relapse and the level of clinical risk are directly correlated with the level of organization in the cancer related gene network. We also explore the variation of the level of organization in the gene network with cancer progression. We find that this variation is non-monotonic, which implies the fitness landscape in the evolution of AML cancer cells is non-trivial. We further find that the hierarchy in gene expression at the time of diagnosis may be a useful biomarker in AML prognosis. (paper)

  2. Is there any interaction between domestic radon exposure and air pollution from traffic in relation to childhood leukemia risk?

    DEFF Research Database (Denmark)

    Bräuner, E.V.; Andersen, Claus Erik; Andersen, H.P.

    2010-01-01

    risk within different strata of air pollution and traffic density. Results: The relative risk for childhood leukemia in association with a 103 Bq/m3-years increase in radon was 1.77 (1.11, 2.82) among those exposed to high levels of NOx and 1.23 (0.79, 1.91) for those exposed to low levels of NOx...

  3. Quantitative assessments of indoor air pollution and the risk of childhood acute leukemia in Shanghai

    International Nuclear Information System (INIS)

    Gao, Yu; Zhang, Yan; Kamijima, Michihiro; Sakai, Kiyoshi; Khalequzzaman, Md; Nakajima, Tamie; Shi, Rong; Wang, Xiaojin; Chen, Didi; Ji, Xiaofan; Han, Kaiyi; Tian, Ying

    2014-01-01

    We investigated the association between indoor air pollutants and childhood acute leukemia (AL). A total of 105 newly diagnosed cases and 105 1:1 gender-, age-, and hospital-matched controls were included. Measurements of indoor pollutants (including nitrogen dioxide (NO 2 ) and 17 types of volatile organic compounds (VOCs)) were taken with diffusive samplers for 64 pairs of cases and controls. Higher concentrations of NO 2 and almost half of VOCs were observed in the cases than in the controls and were associated with the increased risk of childhood AL. The use of synthetic materials for wall decoration and furniture in bedroom was related to the risk of childhood AL. Renovating the house in the last 5 years, changing furniture in the last 5 years, closing the doors and windows overnight in the winter and/or summer, paternal smoking history and outdoor pollutants affected VOC concentrations. Our results support the association between childhood AL and indoor air pollution. - Highlights: • We firstly assessed the effects of indoor air pollution on childhood AL in China. • Indoor air pollutants were assessed by questionnaire and quantitative measurements. • NO 2 and 17 types of VOCs were measured in bedrooms of both cases and controls. • Higher concentrations of indoor air pollutants increased the risk of childhood AL. • Indoor behavioral factors and outdoor pollution might affect indoor air pollution. - Higher concentrations of indoor air pollutants were related to an elevated risk of childhood AL

  4. Parental Perceptions of Obesity and Obesity Risk Associated With Childhood Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Jones, Gary L; McClellan, Wendy; Raman, Sripriya; Sherman, Ashley; Guest, Erin; August, Keith

    2017-07-01

    The prevalence of obesity and related comorbidities in survivors of childhood acute lymphoblastic leukemia (ALL) is well established and ranges anywhere from 29% to 69% depending on the study. We sought to explore the awareness of parents of survivors of childhood ALL regarding the increased risk of obesity and their perceptions regarding the overall health of their child. One hundred twenty-one parents of 99 survivors of pediatric ALL completed surveys regarding perceptions of obesity risk in survivors. Eighty percent of parents of overweight and obese survivors correctly identified their child as "a little overweight" or "overweight." Few parents recalled discussing weight gain (21%) or obesity risk (36%) with their practitioner. Parents that did recall having these discussions and/or reported a decreased level of posttherapy activity in their child were more likely to be concerned about their child's weight status. Improved awareness and education regarding the risk of obesity and associated comorbid conditions may provide an avenue for future prevention of obesity in survivors of pediatric ALL. Discussion and education regarding a healthy lifestyle, including proper diet and exercise, should be incorporated early in routine patient visits.

  5. A new interpretation of the relationship between radiation and risk of leukemia

    International Nuclear Information System (INIS)

    Fritz-Niggli, H.

    1990-01-01

    The article refers to the report, which appeared in England on the increasing occurence of leukemia in youths in the surroundings of nuclear facilities, where their fathers were working. The problem of leukemia clusters is discussed, as well as epidemiological examinations and the exposure of the youths' fathers to radiation, as well as occuring cases of leukemia with survivors of Hiroshima. New studies are encouraged and especially a comparison with groups of people working with mutagenic chemicals

  6. Risk of Subsequent Leukemia After a Solid Tumor in Childhood: Impact of Bone Marrow Radiation Therapy and Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Allodji, Rodrigue S., E-mail: rodrigue.allodji@gustaveroussy.fr [Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif (France); Gustave Roussy, Villejuif (France); Paris Sud University, Orsay (France); Schwartz, Boris; Veres, Cristina; Haddy, Nadia; Rubino, Carole; Le Deley, Marie-Cécile; Labbé, Martine; Diop, Fara; Jackson, Angela; Dayet, Florent; Benabdennebi, Aymen; Llanas, Damien; Vu Bezin, Jérémi [Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif (France); Gustave Roussy, Villejuif (France); Paris Sud University, Orsay (France); Chavaudra, Jean; Lefkopoulos, Dimitri [Gustave Roussy, Villejuif (France); Deutsch, Eric [Gustave Roussy, Villejuif (France); Inserm, UMR 1030, Villejuif (France); Oberlin, Odile [Gustave Roussy, Villejuif (France); Vathaire, Florent de; Diallo, Ibrahima [Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif (France); Gustave Roussy, Villejuif (France); Paris Sud University, Orsay (France)

    2015-11-01

    Purpose: To investigate the roles of radiation therapy and chemotherapy in the occurrence of subsequent leukemia after childhood cancer. Methods and Materials: We analyzed data from a case-control study with 35 cases and 140 controls. The active bone marrow (ABM) was segmented into 19 compartments, and the radiation dose was estimated in each. The chemotherapy drug doses were also estimated to enable adjustments. Models capable of accounting for radiation dose heterogeneity were implemented for analysis. Results: Univariate analysis showed a significant trend in the increase of secondary leukemia risk with radiation dose, after accounting for dose heterogeneity (P=.046). This trend became nonsignificant after adjustment for doses of epipodophyllotoxins, alkylating agents, and platinum compounds and the first cancer on multivariate analysis (P=.388). The role of the radiation dose appeared to be dwarfed, mostly by the alkylating agents (odds ratio 6.9, 95% confidence interval 1.9-25.0). Among the patients who have received >16 Gy to the ABM, the radiogenic risk of secondary leukemia was about 4 times greater in the subgroup with no alkylating agents than in the subgroup receiving ≥10 g/m{sup 2}. Conclusions: Notwithstanding the limitations resulting from the size of our study population and the quite systematic co-treatment with chemotherapy, the use of detailed information on the radiation dose distribution to ABM enabled consideration of the role of radiation therapy in secondary leukemia induction after childhood cancer.

  7. Risk of Subsequent Leukemia After a Solid Tumor in Childhood: Impact of Bone Marrow Radiation Therapy and Chemotherapy

    International Nuclear Information System (INIS)

    Allodji, Rodrigue S.; Schwartz, Boris; Veres, Cristina; Haddy, Nadia; Rubino, Carole; Le Deley, Marie-Cécile; Labbé, Martine; Diop, Fara; Jackson, Angela; Dayet, Florent; Benabdennebi, Aymen; Llanas, Damien; Vu Bezin, Jérémi; Chavaudra, Jean; Lefkopoulos, Dimitri; Deutsch, Eric; Oberlin, Odile; Vathaire, Florent de; Diallo, Ibrahima

    2015-01-01

    Purpose: To investigate the roles of radiation therapy and chemotherapy in the occurrence of subsequent leukemia after childhood cancer. Methods and Materials: We analyzed data from a case-control study with 35 cases and 140 controls. The active bone marrow (ABM) was segmented into 19 compartments, and the radiation dose was estimated in each. The chemotherapy drug doses were also estimated to enable adjustments. Models capable of accounting for radiation dose heterogeneity were implemented for analysis. Results: Univariate analysis showed a significant trend in the increase of secondary leukemia risk with radiation dose, after accounting for dose heterogeneity (P=.046). This trend became nonsignificant after adjustment for doses of epipodophyllotoxins, alkylating agents, and platinum compounds and the first cancer on multivariate analysis (P=.388). The role of the radiation dose appeared to be dwarfed, mostly by the alkylating agents (odds ratio 6.9, 95% confidence interval 1.9-25.0). Among the patients who have received >16 Gy to the ABM, the radiogenic risk of secondary leukemia was about 4 times greater in the subgroup with no alkylating agents than in the subgroup receiving ≥10 g/m"2. Conclusions: Notwithstanding the limitations resulting from the size of our study population and the quite systematic co-treatment with chemotherapy, the use of detailed information on the radiation dose distribution to ABM enabled consideration of the role of radiation therapy in secondary leukemia induction after childhood cancer.

  8. Examination of HFE associations with childhood leukemia risk and extension to other iron regulatory genes.

    Science.gov (United States)

    Kennedy, Amy E; Kamdar, Kala Y; Lupo, Philip J; Okcu, M Fatih; Scheurer, Michael E; Baum, Marianna K; Dorak, M Tevfik

    2014-09-01

    Hereditary hemochromatosis (HFE) variants correlating with body iron levels have shown associations with cancer risk, including childhood acute lymphoblastic leukemia (ALL). Using a multi-ethnic sample of cases and controls from Houston, TX, we examined two HFE variants (rs1800562 and rs1799945), one transferrin receptor gene (TFRC) variant (rs3817672) and three additional iron regulatory gene (IRG) variants (SLC11A2 rs422982; TMPRSS6 rs855791 and rs733655) for their associations with childhood ALL. Being positive for either of the HFE variants yielded a modestly elevated odds ratio (OR) for childhood ALL risk in males (1.40, 95% CI=0.83-2.35), which increased to 2.96 (95% CI=1.29-6.80) in the presence of a particular TFRC genotype for rs3817672 (P interaction=0.04). The TFRC genotype also showed an ethnicity-specific association, with increased risk observed in non-Hispanic Whites (OR=2.54, 95% CI=1.05-6.12; P interaction with ethnicity=0.02). The three additional IRG SNPs all showed individual risk associations with childhood ALL in males (OR=1.52-2.60). A polygenic model based on the number of variant alleles in five IRG SNPs revealed a linear increase in risk among males with the increasing number of variants possessed (OR=2.0 per incremental change, 95% CI=1.29-3.12; P=0.002). Our results replicated previous HFE risk associations with childhood ALL in a US population and demonstrated novel associations for IRG SNPs, thereby strengthening the hypothesis that iron excess mediated by genetic variants contributes to childhood ALL risk. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Outcome of acute myeloid leukemia and high-risk myelodysplastic syndrome according to health insurance status.

    Science.gov (United States)

    Al-Ameri, Ali; Anand, Ankit; Abdelfatah, Mohamed; Kanaan, Zeyad; Hammonds, Tracy; Haller, Nairmeen; Cherry, Mohamad

    2014-12-01

    Age, cytogenetic status, and molecular features are the most important prognostic factors in acute myeloid leukemia (AML). This study aimed to analyze the outcomes of patients with AML or high-risk myelodysplastic syndrome (MDS) according to insurance status. A retrospective chart review was performed, covering all patients with AML and high-risk MDS evaluated and treated at Akron General Medical Center between 2002 and 2012. A Cox regression model was analyzed to account for survival over time, adjusted for insurance type, while controlling for patient age at diagnosis and patient risk of mortality. A total of 130 adult patients (age ≥ 18 years) were identified. Insurance information was available for 97 patients enrolled in the study; 3 were excluded because of self-pay status. Cox regression analysis with insurance type as the predictor found that overall survival declines over time and that the rate of decline may be influenced by insurance type (χ(2)(2) = 6.4; P = .044). The likelihood of survival in patients with Medicaid or Medicare without supplemental insurance was .552 (95% CI, .338-.903; P = .018) times the likelihood in patients who had Medicare with supplemental insurance. To explain the difference, variables of age, gender, and risk of mortality were added to the model. Age and risk of mortality were found to be significant predictors of survival. The addition of insurance type to the model did not significantly contribute (χ(2)(3) = 3.83; P = .147). No significant difference in overall survival was observed when patients with AML or high-risk MDS were analyzed according to their health insurance status. The overall survival was low in this study compared with the national average. Early referral to a specialized center or possible clinical trial enrollment may be a good alternative to improve outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities

    DEFF Research Database (Denmark)

    Möllgård, Lars; Saft, Leonie; Treppendahl, Marianne Bach

    2011-01-01

    Background Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ...... hybridization for del(5q31). DESIGN AND METHODS: Twenty-eight patients at diagnosis or with relapsed disease and not eligible for standard therapy (16 with acute myeloid leukemia, 12 with intermediate-risk 2 or high-risk myelodysplastic syndrome) were enrolled in this prospective phase II multicenter trial...... the 16 weeks of trial responded to treatment. Using the International Working Group criteria for acute myeloid leukemia and myelodysplastic syndrome the overall response rate in treated patients with acute myeloid leukemia was 20% (3/15), while that for patients with myelodysplastic syndrome was 36% (4...

  11. Legal Risk Associated with Electronic Funds Transfer

    OpenAIRE

    Abdulah, Samahir

    2014-01-01

    The past thirty years have seen rapid advances in the technological component of banking services and as a consequence new legal issues have come to the fore, especially with regard to Electronic Fund Transfers (EFTs) which are now used to transfer money around the world, and have made fund transactions between payers and payees easier, faster and more secure. The method involves risks for both banks and customers, due to the possibility of unauthorized payments risks, credit and insolvency p...

  12. Exposure to professional pest control treatments and the risk of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Bailey, Helen D; Armstrong, Bruce K; de Klerk, Nicholas H; Fritschi, Lin; Attia, John; Scott, Rodney J; Smibert, Elizabeth; Milne, Elizabeth

    2011-10-01

    Previous studies suggest that exposure to pesticides increases the risk of childhood acute lymphoblastic leukemia (ALL). The aim of this analysis was to investigate whether professional pest treatments in or around the home before birth or during childhood increased the risk of childhood ALL. Data from 388 cases and 870 frequency-matched controls were analyzed using unconditional logistic regression, adjusting for study matching variables and potential confounders, to calculate odds ratios (ORs). A meta-analysis of our findings with the published findings of previous studies was also conducted. The ORs for any professional pest control treatments were 1.19 (95% CI 0.83, 1.69) in the year before pregnancy, 1.30 (95% CI 0.86, 1.97) during pregnancy and 1.24 (95% CI 0.93, 1.65) for those done after the child's birth. The ORs for exposure after birth were highest when it occurred between the ages of two and three years. ORs were elevated for termite treatments before birth. ORs were higher for pre-B than T cell ALL and for t(12;21) (ETV6-Runx-1) than other cytogenetic sub-types. The pooled OR from a meta-analysis of our study with three previous studies of professional pest control treatments during pregnancy was 1.37 (95% CI 1.00, 1.88). Our results, and those of our meta-analysis, provide some evidence of a modestly increased risk of ALL for professional pest control treatments done during the index pregnancy and possibly in the child's early years. The analysis of pooled data from international collaborations may provide more certainty regarding these potentially important associations. Copyright © 2011 UICC.

  13. Distance to high-voltage power lines and risk of childhood leukemia--an analysis of confounding by and interaction with other potential risk factors.

    Directory of Open Access Journals (Sweden)

    Camilla Pedersen

    Full Text Available We investigated whether there is an interaction between distance from residence at birth to nearest power line and domestic radon and traffic-related air pollution, respectively, in relation to childhood leukemia risk. Further, we investigated whether adjusting for potential confounders alters the association between distance to nearest power line and childhood leukemia. We included 1024 cases aged <15, diagnosed with leukemia during 1968-1991, from the Danish Cancer Registry and 2048 controls randomly selected from the Danish childhood population and individually matched by gender and year of birth. We used geographical information systems to determine the distance between residence at birth and the nearest 132-400 kV overhead power line. Concentrations of domestic radon and traffic-related air pollution (NOx at the front door were estimated using validated models. We found a statistically significant interaction between distance to nearest power line and domestic radon regarding risk of childhood leukemia (p = 0.01 when using the median radon level as cut-off point but not when using the 75th percentile (p = 0.90. We found no evidence of an interaction between distance to nearest power line and traffic-related air pollution (p = 0.73. We found almost no change in the estimated association between distance to power line and risk of childhood leukemia when adjusting for socioeconomic status of the municipality, urbanization, maternal age, birth order, domestic radon and traffic-related air pollution. The statistically significant interaction between distance to nearest power line and domestic radon was based on few exposed cases and controls and sensitive to the choice of exposure categorization and might, therefore, be due to chance.

  14. Contribution of Matrix Metalloproteinase-7 Genotypes to the Risk of Non-solid Tumor, Childhood Leukemia.

    Science.gov (United States)

    Pei, Jen-Sheng; Chou, An-Kuo; Hsu, Pei-Chen; Tsai, Chia-Wen; Chang, Wen-Shin; Wu, Meng-Feng; Wu, Ming-Hsien; Hsia, Te-Chun; Cheng, Shun-Ping; Bau, DA-Tian

    2017-12-01

    The matrix metalloproteinases (MMPs) are important in inflammation and carcinogenesis, and the genotypic role of MMP7 has never been examined in leukemia to date. Therefore, in this study we aimed to evaluate the contribution of the genotypic variants in the promoter region of MMP7 (A-181G and C-153T) to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan. In this case-control study, 266 patients with childhood ALL and 266 non-cancer controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism methodology. The distribution of AA, AG and GG for MMP7 promoter A-181G genotype was 83.5, 12.0 and 4.5% in the childhood ALL group and 89.8%, 9.4 and 0.8% in the non-cancer control group, respectively (p for trend=0.0134), significantly differentially distributed between childhood ALL and control groups. The comparisons in allelic frequency distribution also support the findings that G appears to be the risky allele in childhood ALL. In genotype and gender interaction analysis, it was found that boys carrying the MMP7 A-181G GG and AG+GG genotypes had 9.05- and 2.45-fold odds ratios (ORs) (p=0.0135 and 0.0142, respectively) for childhood ALL compared to those carrying wild-type AA genotype. But these differences were not found in girls. Analysis of genotype interaction with age of onset age showed those aged less than 3.5 years at onset carrying the GG or AG+GG genotypes also had elevated ORs of 8.79- and 2.04-fold (p=0.0150 and 0.0413, respectively) for childhood ALL, but there was no such difference for those having an age at onset of 3.5 years or more. Our results indicate that the MMP7 A-181G genotype interacts with age and gender and may serve as an early and predictive biomarker for childhood ALL. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  15. Chemical exposure and leukemia clusters

    International Nuclear Information System (INIS)

    Cartwright, R.A.

    1992-01-01

    This paper draws attention to the heterogeneous distribution of leukemia in childhood and in adults. The topic of cluster reports and generalized clustering is addressed. These issues are applied to what is known of the risk factor for both adult and childhood leukemia. Finally, the significance of parental occupational exposure and childhood leukemia is covered. (author). 23 refs

  16. Personalized Prognostic Risk Score for Long-Term Survival for Children with Acute Leukemia after Allogeneic Transplantation.

    Science.gov (United States)

    Bitan, Menachem; Ahn, Kwang Woo; Millard, Heather R; Pulsipher, Michael A; Abdel-Azim, Hisham; Auletta, Jeffery J; Brown, Valerie; Chan, Ka Wah; Diaz, Miguel Angel; Dietz, Andrew; Vincent, Marta González; Guilcher, Gregory; Hale, Gregory A; Hayashi, Robert J; Keating, Amy; Mehta, Parinda; Myers, Kasiani; Page, Kristin; Prestidge, Tim; Shah, Nirali N; Smith, Angela R; Woolfrey, Ann; Thiel, Elizabeth; Davies, Stella M; Eapen, Mary

    2017-09-01

    We studied leukemia-free (LFS) and overall survival (OS) in children with acute myeloid (AML, n = 790) and acute lymphoblastic leukemia (ALL, n = 1096) who underwent transplantation between 2000 and 2010 and who survived for at least 1 year in remission after related or unrelated donor transplantation. Analysis of patient-, disease-, and transplantation characteristics and acute and chronic graft-versus-host disease (GVHD) was performed to identify factors with adverse effects on LFS and OS. These data were used to develop risk scores for survival. We did not identify any prognostic factors beyond 4 years after transplantation for AML and beyond 3 years for ALL. Risk score for survival for AML includes age, disease status at transplantation, cytogenetic risk group, and chronic GVHD. For ALL, the risk score includes age at transplantation and chronic GVHD. The 10-year probabilities of OS for AML with good (score 0, 1, or 2), intermediate (score 3), and poor risk (score 4, 5, 6, or 7) were 94%, 87%, and 68%, respectively. The 10-year probabilities of OS for ALL were 89% and 80% for good (score 0 or 1) and poor risk (score 2), respectively. Identifying children at risk for late mortality with early intervention may mitigate some excess late mortality. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  17. Risk of leukemia in first degree relatives of patients with nonsyndromic cleft lip and palate

    Directory of Open Access Journals (Sweden)

    Eduardo GONÇALVES

    2014-01-01

    Full Text Available The aim of this study was to determine the frequency of leukemia in parents of patients with nonsyndromic cleft lip and/or cleft palate (NSCL/P. This case-control study evaluated first-degree family members of 358 patients with NSCL/P and 1,432 subjects without craniofacial alterations or syndromes. Statistical analysis was carried out using Fisher’s test. From the 358 subjects with NSCL/P, 3 first-degree parents had history of leukemia, while 2 out of 1,432 subjects from the unaffected group had a family history of leukemia. The frequency of positive family history of leukemia was not significantly increased in first-degree relatives of patients with NSCL/P.

  18. Electronic Publishing in Science: Changes and Risks.

    Science.gov (United States)

    Kinne, Otto

    1999-01-01

    Discussion of the Internet and the guidance of the World Wide Web Consortium focuses on scientific communication and electronic publishing. Considers the speed of communicating and disseminating information; quality issues; cost; library subscriptions; publishers; and risks and concerns, including the role of editors and reviewers or referees.…

  19. Acute Lymphocytic Leukemia

    Science.gov (United States)

    ... that may increase the risk of acute lymphocytic leukemia include: Previous cancer treatment. Children and adults who've had certain types of chemotherapy and radiation therapy for other kinds of cancer may have an increased ... leukemia. Exposure to radiation. People exposed to very high ...

  20. Clinical impact of leukemic blast heterogeneity at diagnosis in cytogenetic intermediate-risk acute myeloid leukemia

    DEFF Research Database (Denmark)

    Hoffmann, Marianne Hutchings; Klausen, Tobias Wirenfeldt; Boegsted, Martin

    2012-01-01

    Individual cellular heterogeneity within the acute myeloid leukemia (AML) bone marrow samples can be observed by multi parametric flow cytometry analysis (MFC) indicating that immunophenotypic screening for leukemic blast subsets may have prognostic impact.......Individual cellular heterogeneity within the acute myeloid leukemia (AML) bone marrow samples can be observed by multi parametric flow cytometry analysis (MFC) indicating that immunophenotypic screening for leukemic blast subsets may have prognostic impact....

  1. Tobacco smoke and risk of childhood acute non-lymphocytic leukemia: findings from the SETIL study.

    Directory of Open Access Journals (Sweden)

    Stefano Mattioli

    Full Text Available Parental smoking and exposure of the mother or the child to environmental tobacco smoke (ETS as risk factors for Acute non-Lymphocytic Leukemia (AnLL were investigated.Incident cases of childhood AnLL were enrolled in 14 Italian Regions during 1998-2001. We estimated odds ratios (OR and 95% confidence intervals (95%CI conducting logistic regression models including 82 cases of AnLL and 1,044 controls. Inverse probability weighting was applied adjusting for: age; sex; provenience; birth order; birth weight; breastfeeding; parental educational level age, birth year, and occupational exposure to benzene.Paternal smoke in the conception period was associated with AnLL (OR for ≥ 11 cigarettes/day  = 1.79, 95% CI 1.01-3.15; P trend 0.05. An apparent effect modification by maternal age was identified: only children of mothers aged below 30 presented increased risks. We found weak statistical evidence of an association of AnLL with maternal exposure to ETS (OR for exposure>3 hours/day  = 1.85, 95%CI 0.97-3.52; P trend 0.07. No association was observed between AnLL and either maternal smoking during pregnancy or child exposure to ETS.This study is consistent with the hypothesis that paternal smoke is associated with AnLL. We observed statistical evidence of an association between maternal exposure to ETS and AnLL, but believe bias might have inflated our estimates.

  2. Tobacco Smoke and Risk of Childhood Acute Non-Lymphocytic Leukemia: Findings from the SETIL Study

    Science.gov (United States)

    Mattioli, Stefano; Farioli, Andrea; Legittimo, Patrizia; Miligi, Lucia; Benvenuti, Alessandra; Ranucci, Alessandra; Salvan, Alberto; Rondelli, Roberto; Magnani, Corrado

    2014-01-01

    Background Parental smoking and exposure of the mother or the child to environmental tobacco smoke (ETS) as risk factors for Acute non-Lymphocytic Leukemia (AnLL) were investigated. Methods Incident cases of childhood AnLL were enrolled in 14 Italian Regions during 1998–2001. We estimated odds ratios (OR) and 95% confidence intervals (95%CI) conducting logistic regression models including 82 cases of AnLL and 1,044 controls. Inverse probability weighting was applied adjusting for: age; sex; provenience; birth order; birth weight; breastfeeding; parental educational level age, birth year, and occupational exposure to benzene. Results Paternal smoke in the conception period was associated with AnLL (OR for ≥11 cigarettes/day  = 1.79, 95% CI 1.01–3.15; P trend 0.05). An apparent effect modification by maternal age was identified: only children of mothers aged below 30 presented increased risks. We found weak statistical evidence of an association of AnLL with maternal exposure to ETS (OR for exposure>3 hours/day  = 1.85, 95%CI 0.97–3.52; P trend 0.07). No association was observed between AnLL and either maternal smoking during pregnancy or child exposure to ETS. Conclusions This study is consistent with the hypothesis that paternal smoke is associated with AnLL. We observed statistical evidence of an association between maternal exposure to ETS and AnLL, but believe bias might have inflated our estimates. PMID:25401754

  3. Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib

    Science.gov (United States)

    Lipsky, Andrew H.; Farooqui, Mohammed Z.H.; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M.; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U.; Herman, Sarah E. M.; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M.; Lozier, Jay N.; Wiestner, Adrian

    2015-01-01

    Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤2 bleeding-related adverse events in 55% of 85 patients. No grade ≥3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733 PMID

  4. Validation of the EBMT risk score in chronic myeloid leukemia in Brazil and allogeneic transplant outcome.

    Science.gov (United States)

    De Souza, Carmino Antonio; Vigorito, Afonso Celso; Ruiz, Milton Artur; Nucci, Márcio; Dulley, Frederico Luiz; Funcke, Vaneusa; Tabak, Daniel; Azevedo, Alexandre Mello; Byington, Rita; Macedo, Maria Cristina; Saboya, Rosaura; Penteado Aranha, Francisco José; Oliveira, Gislaine Barbosa; Zulli, Roberto; Martins Miranda, Eliana Cristina; Azevedo, Wellington Moraes; Lodi, Fernanda Maria; Voltarelli, Júlio Cesar; Simões, Belinda Pinto; Colturato, Vergílio; De Souza, Mair Pedro; Silla, Lúcia; Bittencourt, Henrique; Piron-Ruiz, Lilian; Maiolino, Angelo; Gratwohl, Alois; Pasquini, Ricardo

    2005-02-01

    The management of chronic myeloid leukemia (CML) has changed radically since the introduction of imatinib therapy. The decision of whether to offer a patient a hematopoietic stem cell transplant (HSCT) must be based on the probability of success of the procedure. The aim of this retrospective analysis of 1,084 CML patients who received an allogeneic HSCT in 10 Brazilian Centers between February 1983 and March 2003 was to validate the EBMT risk score. The study population comprised 647 (60%) males and 437 (40%) females, with a median age of 32 years old (range 1 - 59); 898 (83%) were in chronic phase, 146 (13%) were in accelerated phase and 40 (4%) were in blast crisis; 151 (14%) were younger than 20 years old, 620 (57%) were between 20 and 40 and 313 (29%) were older than 40; 1,025 (94%) received an HLA fully matched sibling transplant and only 59 (6%) received an unrelated transplant. In 283 cases (26%) a male recipient received a graft from a female donor. The interval from diagnosis to transplantation was less than 12 months in 223 (21%) cases and greater in 861 (79%). The overall survival, disease-free survival, transplant-related mortality and relapse incidence were 49%, 50%, 45% and 25%, respectively. Of the 1084 patients, 179 (17%) had a risk score of 0 or 1, 397 (37%) had a score of 2, 345 (32%) had a score of 3, 135 (12%) had a score of 4 and 28 (2%) a score of 5 or 6. The overall survival (OS) rate in patients with risk scores 0-1 and 2 was similar (58% and 55%, respectively) but significantly better than that in patients with scores 3 or more (score 3 - 44%, 4 - 36 % and 5-6 - 27%, respectively) pp<0.001). Disease-free survival (DFS) and transplant related mortality (TRM) in a patients with a score of 3 or more were 46% and 49%, respectively and the relapse rate beyond score 5-6 was 77%. Disease status had a negative impact on all outcomes (OS, DFS, TRM, and relapse). The OS rate for male recipients of a graft from a female donor was 40% compared to 52

  5. ARID5B polymorphism confers an increased risk to acquire specific MLL rearrangements in early childhood leukemia

    Science.gov (United States)

    2014-01-01

    Background Acute leukemia in early age (EAL) is characterized by acquired genetic alterations such as MLL rearrangements (MLL-r). The aim of this case-controlled study was to investigate whether single nucleotide polymorphisms (SNPs) of IKZF1, ARID5B, and CEBPE could be related to the onset of EAL cases (diagnosis). Methods The SNPs (IKZF1 rs11978267, ARID5B rs10821936 and rs10994982, CEBPE rs2239633) were genotyped in 265 cases [169 acute lymphoblastic leukemia (ALL) and 96 acute myeloid leukaemia (AML)] and 505 controls by Taqman allelic discrimination assay. Logistic regression was used to evaluate the association between SNPs of cases and controls, adjusted on skin color and/or age. The risk was determined by calculating odds ratios (ORs) with 95% confidence interval (CI). Results Children with the IKZF1 SNP had an increased risk of developing MLL-germline ALL in white children. The heterozygous/mutant genotype in ARID5B rs10994982 significantly increased the risk for MLL-germline leukemia in white and non-white children (OR 2.60, 95% CI: 1.09-6.18 and OR 3.55, 95% CI: 1.57-8.68, respectively). The heterozygous genotype in ARID5B rs10821936 increased the risk for MLL-r leukemia in both white and non-white (OR 2.06, 95% CI: 1.12-3.79 and OR 2.36, 95% CI: 1.09-5.10, respectively). Furthermore, ARID5B rs10821936 conferred increased risk for MLL-MLLT3 positive cases (OR 7.10, 95% CI:1.54-32.68). Our data do not show evidence that CEBPE rs2239633 confers increased genetic susceptibility to EAL. Conclusions IKZF1 and CEBPE variants seem to play a minor role in genetic susceptibility to EAL, while ARID5B rs10821936 increased the risk of MLL-MLLT3. This result shows that genetic susceptibility could be associated with the differences regarding MLL breakpoints and partner genes. PMID:24564228

  6. Inferior outcomes for black children with high risk acute lymphoblastic leukemia and the impact of socioeconomic variables.

    Science.gov (United States)

    Walsh, Alexandra; Chewning, Joseph; Li, Xuelin; Dai, Chen; Whelan, Kimberly; Madan-Swain, Avi; Waterbor, John; Baskin, Monica L; Goldman, Frederick D

    2017-02-01

    While significant improvements have been made for children with acute lymphoblastic leukemia (ALL) in the United States over the past 20 years, black patients continue to have inferior outcomes. The full impact of socioeconomic variables on outcomes in this minority population is not entirely understood. Disease characteristics, demographic, and socioeconomic status (SES) variables were collected on black (n = 44) and white (n = 178) patients diagnosed at the University of Alabama at Birmingham. Cox proportional hazard regression was used to evaluate the influence of SES and insurance status on survival. As a cohort, 5-year overall survival (OS) was 87% (82-91%), with a median follow-up of 99 months. In univariable analysis, black race was not significantly associated with a higher risk of death or relapse and death. White and black patients with standard-risk leukemia had excellent outcomes, with 97% (91-99%) and 96% (75-99%) 5-year OS, respectively. In contrast, for high-risk disease, white patients had a statistically significant improved 5-year OS rates compared with black patients (79% [68-87%] vs. 52% [28-72%]). Black children were more likely to have public insurance, and, in multivariable analysis, this was associated with a trend toward an improved outcome. Black patients also had poorer census tract-level SES parameters, but these variables were not associated with survival. Our study demonstrates significantly inferior outcomes for black children with high-risk leukemia. These outcome disparities were not related to SES variables, including poverty or private insurance coverage, suggesting the involvement of other factors and highlighting the need for a prospective investigative analysis. © 2016 Wiley Periodicals, Inc.

  7. Risk assessment of integrated electronic health records.

    Science.gov (United States)

    Bjornsson, Bjarni Thor; Sigurdardottir, Gudlaug; Stefansson, Stefan Orri

    2010-01-01

    The paper describes the security concerns related to Electronic Health Records (EHR) both in registration of data and integration of systems. A description of the current state of EHR systems in Iceland is provided, along with the Ministry of Health's future vision and plans. New legislation provides the opportunity for increased integration of EHRs and further collaboration between institutions. Integration of systems, along with greater availability and access to EHR data, requires increased security awareness since additional risks are introduced. The paper describes the core principles of information security as it applies to EHR systems and data. The concepts of confidentiality, integrity, availability, accountability and traceability are introduced and described. The paper discusses the legal requirements and importance of performing risk assessment for EHR data. Risk assessment methodology according to the ISO/IEC 27001 information security standard is described with examples on how it is applied to EHR systems.

  8. Intensification of mercaptopurine/methotrexate maintenance chemotherapy may increase the risk of relapse for some children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Björk, Olle; Glomstein, Anders

    2003-01-01

    by erythrocyte (E) levels of TGN and MTX (including polyglutamates) could improve outcome in childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: A total of 538 children with ALL were randomly assigned to have their oral MP/MTX maintenance therapy adjusted by white cell counts (WBC), E-TGN, and E......-MTX (pharmacology group), or by WBC only (control group). RESULTS: After a median follow-up of 7.8 years, 79 patients had relapsed. Cox regression analysis showed an increased risk of relapse for boys (P =.00003), high WBC at diagnosis (P =.03), pharmacology arm (6.6 times increased relapse hazard for girls), high...

  9. Cured meat, vegetables, and bean-curd foods in relation to childhood acute leukemia risk: a population based case-control study.

    Science.gov (United States)

    Liu, Chen-Yu; Hsu, Yi-Hsiang; Wu, Ming-Tsang; Pan, Pi-Chen; Ho, Chi-Kung; Su, Li; Xu, Xin; Li, Yi; Christiani, David C

    2009-01-13

    Consumption of cured/smoked meat and fish leads to the formation of carcinogenic N-nitroso compounds in the acidic stomach. This study investigated whether consumed cured/smoked meat and fish, the major dietary resource for exposure to nitrites and nitrosamines, is associated with childhood acute leukemia. A population-based case-control study of Han Chinese between 2 and 20 years old was conducted in southern Taiwan. 145 acute leukemia cases and 370 age- and sex-matched controls were recruited between 1997 and 2005. Dietary data were obtained from a questionnaire. Multiple logistic regression models were used in data analyses. Consumption of cured/smoked meat and fish more than once a week was associated with an increased risk of acute leukemia (OR = 1.74; 95% CI: 1.15-2.64). Conversely, higher intake of vegetables (OR = 0.55; 95% CI: 0.37-0.83) and bean-curd (OR = 0.55; 95% CI: 0.34-0.89) was associated with a reduced risk. No statistically significant association was observed between leukemia risk and the consumption of pickled vegetables, fruits, and tea. Dietary exposure to cured/smoked meat and fish may be associated with leukemia risk through their contents of nitrites and nitrosamines among children and adolescents, and intake of vegetables and soy-bean curd may be protective.

  10. Potentially functional polymorphism in IL-23 receptor and risk of acute myeloid leukemia in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Xifeng Qian

    Full Text Available The interleukin-23 (IL-23 and its receptor (IL-23R mediate the direct antitumor activities in human hematologic malignancies including pediatric acute leukemia. Two potentially functional genetic variants (IL-23R rs1884444 T>G and rs6682925 T>C have been found to contribute to solid cancer susceptibility. In this study, we conducted a case-control study including 545 acute myeloid leukemia (AML patients and 1,146 cancer-free controls in a Chinese population to assess the association between these two SNPs and the risk of AML. We found that IL-23R rs1884444 TG/GG and rs6682925 TC/CC variant genotypes were associated with significantly increased risk of AML [rs1884444: adjusted odds ratio (OR = 1.28, 95% confidence interval (CI = 1.01-1.62; rs6682925: adjusted OR = 1.30, 95%CI = 1.01-1.67], compared to their corresponding wild-type homozygotes, respectively. These findings indicated that genetic variants in IL-23R may contribute to AML risk in our Chinese population.

  11. Genomic profiling of thousands of candidate polymorphisms predicts risk of relapse in 778 Danish and German childhood acute lymphoblastic leukemia patients

    DEFF Research Database (Denmark)

    Wesolowska, Agata; Borst, L.; Dalgaard, Marlene Danner

    2015-01-01

    Childhood acute lymphoblastic leukemia survival approaches 90%. New strategies are needed to identify the 10–15% who evade cure. We applied targeted, sequencing-based genotyping of 25 000 to 34 000 preselected potentially clinically relevant singlenucleotide polymorphisms (SNPs) to identify host...... associated with risk of relapse across protocols. SNP and biologic pathway level analyses associated relapse risk with leukemia aggressiveness, glucocorticosteroid pharmacology/response and drug transport/metabolism pathways. Classification and regression tree analysis identified three distinct risk groups...... defined by end of induction residual leukemia, white blood cell count and variants in myeloperoxidase (MPO), estrogen receptor 1 (ESR1), lamin B1 (LMNB1) and matrix metalloproteinase-7 (MMP7) genes, ATP-binding cassette transporters and glucocorticosteroid transcription regulation pathways. Relapse rates...

  12. Exposure to ambient air pollution in Canada and the risk of adult leukemia

    International Nuclear Information System (INIS)

    Winters, Nicholas; Goldberg, Mark S.; Hystad, Perry; Villeneuve, Paul J.; Johnson, Kenneth C.

    2015-01-01

    There is a paucity of studies investigating adult leukemia and air pollution. To address this gap, we analyzed data from a Canadian population-based case–control study conducted in 1994–1997. Cases were 1064 adults with incident leukemia and controls were 5039 healthy adults. We used data from satellites and fixed-site monitoring stations to estimate residential concentrations of NO 2 and fine particulate matter (PM 2.5 ) for the period prior to diagnosis, starting in 1975 and ending in 1994. We modeled the average annual exposure of each subject. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated using logistic regression, adjusted for age, gender, province, smoking, education, body mass index, income, and self-reported exposures to ionizing radiation and benzene. We found an ‘n-shaped’ response function between exposure to NO 2 and all forms of leukemia: from the tenth percentile to the median (4.51 to 14.66 ppb), the OR was 1.20; 95% CI: 0.97–1.48 and from the 75th percentile to the 90th (22.75 to 29.7 ppb), the OR was 0.79; 95% CI 0.68–0.93. For PM 2.5 we found a response function consistent with a linear model, with an OR per 10 μg/m 3 of 0.97 (95% CI 0.75–1.26). For chronic lymphocytic leukemia we found response functions that were consistent with a simple linear model, with an OR per 5 ppb of NO 2 of 0.93 (95% CI 0.86–1.00) and an OR per 10 μg/m 3 of PM 2.5 of 0.62 (95% CI 0.42–0.93). In summary, for chronic lymphocytic leukemia we found no evidence of an association with air pollution and with all forms of leukemia we found weak evidence of an association only at low concentrations of NO 2 . It is possible that these inconsistent results may have arisen because of unaccounted urban/rural differences or possibly from a selection effect, especially among controls. - Highlights: • Analyzed associations between incidence of adult leukemia and PM • We used 20-year residential histories to estimate average annual

  13. Exposure to ambient air pollution in Canada and the risk of adult leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Winters, Nicholas [Department of Medicine, McGill University, Montreal, Quebec (Canada); Goldberg, Mark S., E-mail: mark.goldberg@mcgill.ca [Department of Medicine, McGill University, Montreal, Quebec (Canada); Division of Clinical Epidemiology, McGill University Health Centre, 687 Pine Ave. W., R4.29, Montreal, Quebec H3A 1A1 (Canada); Hystad, Perry [College of Public Health and Human Sciences, Oregon State University, Corvallis, OR (United States); Villeneuve, Paul J. [Department of Health Sciences, Carleton University, Ottawa, Ontario (Canada); Johnson, Kenneth C. [Science Integration Division, Centre for Chronic Disease Prevention and Control, Public Health Agency of Canada, Ottawa, Ontario (Canada)

    2015-09-01

    There is a paucity of studies investigating adult leukemia and air pollution. To address this gap, we analyzed data from a Canadian population-based case–control study conducted in 1994–1997. Cases were 1064 adults with incident leukemia and controls were 5039 healthy adults. We used data from satellites and fixed-site monitoring stations to estimate residential concentrations of NO{sub 2} and fine particulate matter (PM{sub 2.5}) for the period prior to diagnosis, starting in 1975 and ending in 1994. We modeled the average annual exposure of each subject. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated using logistic regression, adjusted for age, gender, province, smoking, education, body mass index, income, and self-reported exposures to ionizing radiation and benzene. We found an ‘n-shaped’ response function between exposure to NO{sub 2} and all forms of leukemia: from the tenth percentile to the median (4.51 to 14.66 ppb), the OR was 1.20; 95% CI: 0.97–1.48 and from the 75th percentile to the 90th (22.75 to 29.7 ppb), the OR was 0.79; 95% CI 0.68–0.93. For PM{sub 2.5} we found a response function consistent with a linear model, with an OR per 10 μg/m{sup 3} of 0.97 (95% CI 0.75–1.26). For chronic lymphocytic leukemia we found response functions that were consistent with a simple linear model, with an OR per 5 ppb of NO{sub 2} of 0.93 (95% CI 0.86–1.00) and an OR per 10 μg/m{sup 3} of PM{sub 2.5} of 0.62 (95% CI 0.42–0.93). In summary, for chronic lymphocytic leukemia we found no evidence of an association with air pollution and with all forms of leukemia we found weak evidence of an association only at low concentrations of NO{sub 2}. It is possible that these inconsistent results may have arisen because of unaccounted urban/rural differences or possibly from a selection effect, especially among controls. - Highlights: • Analyzed associations between incidence of adult leukemia and PM • We used 20-year residential

  14. Allogeneic bone marrow transplantation with conditioning regimen to total body irradiation + thiotepa + melphalan for 35 patients with high-risk leukemia

    International Nuclear Information System (INIS)

    Yumura-Yagi, Keiko; Inoue, Masami; Okamura, Takayuki

    1997-01-01

    Thirty-five children with high-risk leukemia received an allogeneic bone marrow transplantation (BMT) following a pre-conditioning regimen consisting of total body irradiation, thiotepa and melphalan. Twenty-one patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 acute undifferentiated leukemia, 2 acute mixed lineage leukemia, 2 myelodysplastic syndrome and 2 juvenile chronic myeloid leukemia. Sixteen patients received BMT while in complete remission (CR), but 19 were not in CR. Eighteen patients received transplants from HLA-matched related donors, 15 from unrelated donors and 2 from HLA-mismatched related donors. Cyclosporin±methotrexate was used for graft-versus-host disease (GVHD) prophylaxis in the BMTs from related donors and tacrolimus±prednisolone in the BMTs from unrelated donors. Transplant-related death occurred in 12 patients; 5 acute GVHD, 4 infections (3 fungal infections, 1 Cytomegalovirus pneumonia), 1 intracranial haemorrhage and 2 chronic GVHD. Relapses were observed in 6 patients (69, 168, 175, 222, 275 and 609 days post BMT). Event-free survival rate at 2 years is 38.1% in CR patients and 36.9% in nonCR patients. (author)

  15. Letter regarding Zhao et al. entitled " DPYD gene polymorphisms are associated with risk and chemotherapy prognosis in pediatric patients with acute lymphoblastic leukemia".

    Science.gov (United States)

    Deenen, Maarten J; Henricks, Linda M; Sonke, Gabe S; Schellens, Jan Hm; Meulendijks, Didier

    2017-06-01

    Zhao et al. investigated the association between germline genetic polymorphisms in DPYD, the gene encoding dihydropyrimidine dehydrogenase, and (1) the risk of developing pediatric acute lymphoblastic leukemia and (2) outcome of acute lymphoblastic leukemia following the treatment with 5-fluorouracil plus oxaliplatin (FOLFOX). The authors found that the common DPYD variant c.85T>C (rs1801265, DPYD*9A) was significantly associated with (1) risk of developing pediatric acute lymphoblastic leukemia, (2) complete response rate, (3) event-free survival, and (4) treatment-related toxicity. The authors conclude that patients carrying the c.85T>C C allele have an increased risk of developing acute lymphoblastic leukemia and have inferior outcome, and that DPYD c.85T>C can be used as a guide for individualized treatment and the decision to utilize 5-fluorouracil in acute lymphoblastic leukemia patients. In our view, the published article gives rise to multiple critical issues regarding the study's rationale and the methodology used, which strongly question the validity of the authors' conclusions.

  16. Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Al-Modhwahi, Ibrahim; Andersen, Mette Klarskov

    2009-01-01

    Among 1614 children with acute lymphoblastic leukemia (ALL) treated with the Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL-92 protocol, 20 patients developed a second malignant neoplasm (SMN) with a cumulative risk of 1.6% at 12 years from the diagnosis of ALL. Nine of the 16...... acute myeloid leukemias or myelodysplastic syndromes had monosomy 7 (n = 7) or 7q deletions (n = 2). In Cox multivariate analysis, longer duration of oral 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy (P = .02; longest for standard-risk patients) and presence of high hyperdiploidy (P...

  17. Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib

    DEFF Research Database (Denmark)

    Lipsky, Andrew H; Farooqui, Mohammed Z H; Tian, Xin

    2015-01-01

    Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated t......Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator......-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤2 bleeding-related adverse events in 55% of 85 patients. No grade ≥3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months...... 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not...

  18. Chronic myelogenous leukemia (CML)

    Science.gov (United States)

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... nuclear disaster. It takes many years to develop leukemia from radiation exposure. Most people treated for cancer ...

  19. Epidemiological survey of radiation workers. Risk of leukemia and solid cancer by low level radiation exposure

    International Nuclear Information System (INIS)

    Tatsumi, Kouichi

    2011-01-01

    An interim report on the epidemiological survey of cohort involving radiation workers in the nuclear power plants in Japan was introduced. It consists of eight chapters such as introduction, the objects of mortality rate survey from death causes and creating a cohort, the method of tracking the life and death, analytical methods of mortality rate, analytical results, confounded effects of life style, discussion: contrast the report on the mortality rate of solid cancer except leukemia in Japan and other countries and the conclusions. The subjects of mortality rate of the forth survey were about 277,000 workers including from the first to the third survey. In a prospective cohort study, 203,904 workers were screened for analytical study, and they included 14,224 deaths (5,711 from malignant neoplasm, 6,310 from nonmalignant neoplasm and 1,995 from extrinsic death). The analytical results were shown by three types of death caused from leukemia, malignant neoplasm except for leukemia and nonmalignant neoplasm. Analytical results of the mortality rate from death caused in third and forth study, change of analytical results from the first to the forth observation period were illustrated. (S.Y.)

  20. Acute myeloid leukemia in the era of precision medicine: recent advances in diagnostic classification and risk stratification

    International Nuclear Information System (INIS)

    Kansal, Rina

    2016-01-01

    Acute myeloid leukemia (AML) is a genetically heterogeneous myeloid malignancy that occurs more commonly in adults, and has an increasing incidence, most likely due to increasing age. Precise diagnostic classification of AML requires clinical and pathologic information, the latter including morphologic, immunophenotypic, cytogenetic and molecular genetic analysis. Risk stratification in AML requires cytogenetics evaluation as the most important predictor, with genetic mutations providing additional necessary information. AML with normal cytogenetics comprises about 40%-50% of all AML, and has been intensively investigated. The currently used 2008 World Health Organization classification of hematopoietic neoplasms has been proposed to be updated in 2016, also to include an update on the classification of AML, due to the continuously increasing application of genomic techniques that have led to major advances in our knowledge of the pathogenesis of AML. The purpose of this review is to describe some of these recent major advances in the diagnostic classification and risk stratification of AML

  1. Acute myeloid leukemia in the era of precision medicine: recent advances in diagnostic classification and risk stratification.

    Science.gov (United States)

    Kansal, Rina

    2016-03-01

    Acute myeloid leukemia (AML) is a genetically heterogeneous myeloid malignancy that occurs more commonly in adults, and has an increasing incidence, most likely due to increasing age. Precise diagnostic classification of AML requires clinical and pathologic information, the latter including morphologic, immunophenotypic, cytogenetic and molecular genetic analysis. Risk stratification in AML requires cytogenetics evaluation as the most important predictor, with genetic mutations providing additional necessary information. AML with normal cytogenetics comprises about 40%-50% of all AML, and has been intensively investigated. The currently used 2008 World Health Organization classification of hematopoietic neoplasms has been proposed to be updated in 2016, also to include an update on the classification of AML, due to the continuously increasing application of genomic techniques that have led to major advances in our knowledge of the pathogenesis of AML. The purpose of this review is to describe some of these recent major advances in the diagnostic classification and risk stratification of AML.

  2. Auger electron-emitting "1"1"1In-DTPA-NLS-CSL360 radioimmunoconjugates are cytotoxic to human acute myeloid leukemia (AML) cells displaying the CD123"+/CD131"− phenotype of leukemia stem cells

    International Nuclear Information System (INIS)

    Gao, Catherine; Leyton, Jeffrey V.; Schimmer, Aaron D.; Minden, Mark; Reilly, Raymond M.

    2016-01-01

    Chimeric IgG_1 monoclonal antibody CSL360 recognizes the CD123"+/CD131"− phenotype expressed by leukemic stem cells (LSC). Auger electron-emitting "1"1"1In-DTPA-NLS-CSL360 radioimmunoconjugates incorporating nuclear translocation sequence (NLS) peptides bound specifically to Raji cells transfected with CD123 and exhibited a K_D of 11 nmols/L in a competition receptor-binding assay using CD123-transfected CHO cells. "1"1"1In-DTPA-NLS-CSL360 was bound, internalized and transported to the nucleus of human AML-5 myeloid leukemia cells. The clonogenic survival of AML-5 cells was reduced by "1"1"1In-DTPA-NLS-CSL360 up to 3.7-fold. Isotype control "1"1"1In-DTPA-chIgG_1 was 2-fold less cytotoxic, and unlabeled CSL360, DTPA-NLS-CSL360 or free "1"1"1In acetate did not decrease cell survival. These results are promising for further evaluation of "1"1"1In-DTPA-NLS-CSL360 for Auger electron radioimmunotherapy of AML targeting the critical LSC subpopulation. - Highlights: • "1"1"1In-DTPA-NLS-CSL360 the CD123"+/CD131"− phenotype of leukemic stem cells (LSC). • "1"1"1In-DTPA-NLS-CSL360 was bound, internalized and imported into the nucleus of AML-5 leukemia cells. • "1"1"1In-DTPA-NLS-CSL360 reduced the clonogenic survival of AML-5 leukemia cells by 4-fold.

  3. Allogeneic hematopoietic cell transplantation in first remission abrogates poor outcomes associated with high-risk pediatric acute myeloid leukemia.

    Science.gov (United States)

    Burke, Michael J; Wagner, John E; Cao, Qing; Ustun, Celalettin; Verneris, Michael R

    2013-07-01

    Despite remission rates of approximately 85% for children diagnosed with acute myeloid leukemia (AML), greater than 40% will die from relapsed disease. Patients with poor-risk molecular/cytogenetics and/or inadequate response to up-front therapy are typically considered high-risk (HR) and historically have poor outcomes with chemotherapy alone. We investigated whether allogeneic hematopoietic cell transplantation (allo-HCT) with best available donor in first remission (CR1) would abrogate the poor outcomes associated with HR AML in children and young adults treated with chemotherapy. We reviewed the outcomes of 50 consecutive children and young adults (ages 0 to 30 years) with AML who received a myeloablative allo-HCT between 2001 and 2010. Thirty-six patients (72%) were HR, defined as having FLT3-ITD mutations, 11q23 MLL rearrangements, chromosome 5 or 7 abnormalities, induction failure, and/or having persistent disease. The majority of patients received cyclophosphamide and total body irradiation conditioning, and graft-versus-host-disease (GVHD) prophylaxis was cyclosporine based. Transplantation outcomes for HR patients were compared to standard-risk patients, with no significant differences observed in overall survival (72% versus 78%, P = .72), leukemia-free survival (69% versus 79%, P = .62), relapse (11% versus 7%, P = .71), or treatment-related mortality (17% versus 14%, P = .89). Children and young adults with HR-AML have comparable outcomes to standard-risk patients following allo-HCT in CR1. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  4. The role of multiple regression and exploratory data analysis in the development of leukemia incidence risk models for comparison of radionuclide air stack emissions from nuclear and coal power industries

    International Nuclear Information System (INIS)

    Prybutok, V.R.

    1995-01-01

    Risk associated with power generation must be identified to make intelligent choices between alternate power technologies. Radionuclide air stack emissions for a single coal plant and a single nuclear plant are used to compute the single plant leukemia incidence risk and total industry leukemia incidence risk. Leukemia incidence is the response variable as a function of radionuclide bone dose for the six proposed dose response curves considered. During normal operation a coal plant has higher radionuclide emissions than a nuclear plant and the coal industry has a higher leukaemia incidence risk than the nuclear industry, unless a nuclear accident occurs. Variation of nuclear accident size allows quantification of the impact of accidents on the total industry leukemia incidence risk comparison. The leukemia incidence risk is quantified as the number of accidents of a given size for the nuclear industry leukemia incidence risk to equal the coal industry leukemia incidence risk. The general linear model is used to develop equations that relate the accident frequency required for equal industry risks to the magnitude of the nuclear emission. Exploratory data analysis revealed that the relationship between the natural log of accident number versus the natural log of accident size is linear. (Author)

  5. Distance to High-Voltage Power Lines and Risk of Childhood Leukemia – an Analysis of Confounding by and Interaction with Other Potential Risk Factors

    DEFF Research Database (Denmark)

    Pedersen, Camilla; Bräuner, Elvira V; Rod, Naja Hulvej

    2014-01-01

    . We used geographical information systems to determine the distance between residence at birth and the nearest 132-400 kV overhead power line. Concentrations of domestic radon and traffic-related air pollution (NOx at the front door) were estimated using validated models. We found a statistically......We investigated whether there is an interaction between distance from residence at birth to nearest power line and domestic radon and traffic-related air pollution, respectively, in relation to childhood leukemia risk. Further, we investigated whether adjusting for potential confounders alters...

  6. Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities

    DEFF Research Database (Denmark)

    Möllgård, Lars; Saft, Leonie; Treppendahl, Marianne Bach

    2011-01-01

    Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ hybridization...

  7. Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Simonsson, Bengt; Gedde-Dahl, Tobias; Markevärn, Berit

    2011-01-01

    Biologic and clinical observations suggest that combining imatinib with IFN-α may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remissio...

  8. Factors Associated with Long-Term Risk of Relapse after Unrelated Cord Blood Transplantation in Children with Acute Lymphoblastic Leukemia in Remission.

    Science.gov (United States)

    Page, Kristin M; Labopin, Myriam; Ruggeri, Annalisa; Michel, Gerard; Diaz de Heredia, Cristina; O'Brien, Tracey; Picardi, Alessandra; Ayas, Mouhab; Bittencourt, Henrique; Vora, Ajay J; Troy, Jesse; Bonfim, Carmen; Volt, Fernanda; Gluckman, Eliane; Bader, Peter; Kurtzberg, Joanne; Rocha, Vanderson

    2017-08-01

    For pediatric patients with acute lymphoblastic leukemia (ALL), relapse is an important cause of treatment failure after unrelated cord blood transplant (UCBT). Compared with other donor sources, relapse is similar or even reduced after UCBT despite less graft-versus-host disease (GVHD). We performed a retrospective analysis to identify risk factors associated with the 5-year cumulative incidence of relapse after UCBT. In this retrospective, registry-based study, we examined the outcomes of 640 children (leukemia-free survival (LFS), and relapse were 59%, 52%, and 23%, respectively. In multivariate analysis (MVA), acute GVHD (grades II to IV) and TBI protected against relapse. In patients in CR2, rates of 5-year OS, LFS, and the cumulative incidence of relapse were 46%, 44%, and 28%, respectively. In MVA, longer duration from diagnosis to UCBT (≥30 months) and TBI were associated with decreased relapse risk. Importantly, receiving a fully HLA matched graft was a strong risk factor for increased relapse in MVA. An exploratory analysis of all 640 patients supported the important association between the presence of acute GVHD and less relapse but also demonstrated an increased risk of nonrelapse mortality. In conclusion, the impact of GVHD as a graft-versus-leukemia marker is evident in pediatric ALL after UCBT. Strategies that promote graft-versus-leukemia while harnessing GVHD should be further investigated. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  9. Risk of leukemia associated with the first course of cancer treatment: an analysis of the Surveillance, Epidemiology, and End Results Program experience

    International Nuclear Information System (INIS)

    Curtis, R.E.; Hankey, B.F.; Myers, M.H.; Young, J.L. Jr.

    1984-01-01

    The risk of leukemia associated with the first course of cancer treatment was evaluated in over 440,000 patients diagnosed during 1973-80 (average follow-up . 1.91 yr) from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Although the reporting of the first course of therapy probably was incomplete, 34 acute nonlymphocytic leukemias (ANLL) developed compared with 7.6 expected among 70,674 patients known to receive initial chemotherapy [relative risk (RR) . 4.5, 95% confidence interval (Cl) . 3.1-6.3]. Significant ANLL excesses were observed following chemotherapy for breast cancer (RR . 8.1), ovarian cancer (RR . 22.2), and multiple myeloma (RR . 9.5). Patients initially treated with radiation (with no record of chemotherapy) also had a significantly increased ANLL risk; 45 leukemias occurred versus 17.9 expected (RR . 2.5, 95% Cl . 1.8-3.4). In this group, excess ANLL were found following irradiation for uterine corpus cancer (RR . 4.0). Kidney and renal pelvis cancer patients had a twofold leukemia risk (all types) that was unrelated to treatment (RR . 2.2)

  10. Evaluating the Role of Birth Weight and Gestational Age on Acute Lymphoblastic Leukemia Risk Among Those of Hispanic Ethnicity.

    Science.gov (United States)

    Barahmani, Nadia; Dorak, M Tevfik; Forman, Michele R; Sprehe, Michael R; Scheurer, Michael E; Bondy, Melissa L; Okcu, M Fatih; Lupo, Philip J

    2015-01-01

    High birth weight is an established risk factor for childhood acute lymphoblastic leukemia (ALL), especially in children younger than 5 years of age at diagnosis. The goal of this study was to explore the association between being born large for gestational age and the risk for ALL by race/ethnicity to determine if the role of this risk factor differed by these characteristics. The authors compared birth certificate data of 575 children diagnosed with ALL who were younger than 5 years and included in the Texas Cancer Registry, Texas Department of Health, between the years 1995 and 2003 with 11,379 controls matched by birth year. Stratified odds ratios were calculated for risk of ALL by birth weight for gestational age, categorized in 3 groups, small, appropriate, and large for gestational age (SGA, AGA, and LGA, respectively), for each race/ethnicity group. The risk of developing ALL was higher among Hispanics who were LGA (odds ratio [OR] = 1.90, 95% confidence interval [CI]: 1.34-2.68) compared with LGA non-Hispanic whites (OR = 1.27, 95% CI: 0.87-1.86) after adjusting for infant gender, year of birth, maternal age, birth order, and presence of Down syndrome. However, the difference was not statistically significant. These results suggest that there may be differences in the association between higher growth in utero and risk of childhood ALL among Hispanics versus non-Hispanic whites.

  11. Childhood Leukemia and Primary Prevention

    Science.gov (United States)

    Whitehead, Todd P.; Metayer, Catherine; Wiemels, Joseph L.; Singer, Amanda W.; Miller, Mark D.

    2016-01-01

    Leukemia is the most common pediatric cancer, affecting 3,800 children per year in the United States. Its annual incidence has increased over the last decades, especially among Latinos. Although most children diagnosed with leukemia are now cured, many suffer long-term complications, and primary prevention efforts are urgently needed. The early onset of leukemia – usually before age five – and the presence at birth of “pre-leukemic” genetic signatures indicate that pre- and postnatal events are critical to the development of the disease. In contrast to most pediatric cancers, there is a growing body of literature – in the United States and internationally – that has implicated several environmental, infectious, and dietary risk factors in the etiology of childhood leukemia, mainly for acute lymphoblastic leukemia, the most common subtype. For example, exposures to pesticides, tobacco smoke, solvents, and traffic emissions have consistently demonstrated positive associations with the risk of developing childhood leukemia. In contrast, intake of vitamins and folate supplementation during the pre-conception period or pregnancy, breastfeeding, and exposure to routine childhood infections have been shown to reduce the risk of childhood leukemia. Some children may be especially vulnerable to these risk factors, as demonstrated by a disproportionate burden of childhood leukemia in the Latino population of California. The evidence supporting the associations between childhood leukemia and its risk factors – including pooled analyses from around the world and systematic reviews – is strong; however, the dissemination of this knowledge to clinicians has been limited. To protect children’s health, it is prudent to initiate programs designed to alter exposure to well-established leukemia risk factors rather than to suspend judgement until no uncertainty remains. Primary prevention programs for childhood leukemia would also result in the significant co

  12. Ionizing radiation exposures in treatments of solid neoplasms are not associated with subsequent increased risks of chronic lymphocytic leukemia.

    Science.gov (United States)

    Radivoyevitch, Tomas; Sachs, Rainer K; Gale, Robert Peter; Smith, Mitchell R; Hill, Brian T

    2016-04-01

    Exposure to ionizing radiation is not thought to cause chronic lymphocytic leukemia (CLL). Challenging this notion are recent data suggesting CLL incidence may be increased by radiation exposure from the atomic bombs (after many decades), uranium mining and nuclear power facility accidents. To assess the effects of therapeutic ionizing radiation for the treatment of solid neoplasms we studied CLL risks in data from the Surveillance, Epidemiology, and End Results (SEER) Program. Specifically, we compared the risks of developing CLL in persons with a 1(st) non-hematologic cancer treated with or without ionizing radiation. We controlled for early detection effects on CLL risk induced by surveillance after 1(st) cancer diagnoses by forming all-time cumulative CLL relative risks (RR). We estimate such CLL RR to be 1.20 (95% confidence interval, 1.17, 1.23) for persons whose 1(st) cancer was not treated with ionizing radiation and 1.00 (0.96, 1.05) for persons whose 1(st) cancer was treated with ionizing radiations. These results imply that diagnosis of a solid neoplasm is associated with an increased risk of developing CLL only in persons whose 1(st) cancer was not treated with radiation therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Treatment results of the Tokai-POSG 8610HR pilot protocol for children with high-risk acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Hongo, Teruaki; Inoue, Noriko [Hamamatsu Medical Univ., Shizuoka (Japan); Horibe, Keizo [and others

    1997-10-01

    We reported the treatment results of Tokai-POSG 8610HR pilot protocol for children with high-risk acute lymphoblastic leukemia (ALL). From Oct. 1986 to Jan. 1991, 43 eligible children were enrolled, who had one or more following high-risk factors: age{>=}10 years old, initial white blood cell count (WBC) of 50,000/{mu}l or more, and extramedullary leukemia. All patients received induction therapy consisting of vincristine, dexamethasone, cyclophosphamide and daunorubicin, followed by central nervous system prophylaxis by 24 Gy cranial irradiation, consolidation therapy and cyclic maintenance by multidrugs for 3 years after diagnosis. Complete remission was achieved in 39 patients. The 5-year event-free survival (EFS) rate was 72.6{+-}7.1%. The only factor of an adverse association with EFS was a initial WBC of 10,000/{mu}l or more (p=0.002) in the 24 patients who were 10 years old or over. The factors related to a negative survival were male gender (p=0.031) and an initial WBC of 10,000/{mu}l or more (p=0.0012) in 43 patients. The major toxicities of the therapy were pancreatitis and allergic reaction due to{sub L}-ASP administration, and growth hormone deficiency due to cranial irradiation. Tokai 8610HR pilot protocol was a promising regimen, but further intensive chemotherapy was needed for improvement or the prognosis of the older patients with high initial WBC greater than 10,000/{mu}l. (author)

  14. Treatment results of the Tokai-POSG 8610HR pilot protocol for children with high-risk acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Hongo, Teruaki; Inoue, Noriko; Horibe, Keizo

    1997-01-01

    We reported the treatment results of Tokai-POSG 8610HR pilot protocol for children with high-risk acute lymphoblastic leukemia (ALL). From Oct. 1986 to Jan. 1991, 43 eligible children were enrolled, who had one or more following high-risk factors: age≥10 years old, initial white blood cell count (WBC) of 50,000/μl or more, and extramedullary leukemia. All patients received induction therapy consisting of vincristine, dexamethasone, cyclophosphamide and daunorubicin, followed by central nervous system prophylaxis by 24 Gy cranial irradiation, consolidation therapy and cyclic maintenance by multidrugs for 3 years after diagnosis. Complete remission was achieved in 39 patients. The 5-year event-free survival (EFS) rate was 72.6±7.1%. The only factor of an adverse association with EFS was a initial WBC of 10,000/μl or more (p=0.002) in the 24 patients who were 10 years old or over. The factors related to a negative survival were male gender (p=0.031) and an initial WBC of 10,000/μl or more (p=0.0012) in 43 patients. The major toxicities of the therapy were pancreatitis and allergic reaction due to L -ASP administration, and growth hormone deficiency due to cranial irradiation. Tokai 8610HR pilot protocol was a promising regimen, but further intensive chemotherapy was needed for improvement or the prognosis of the older patients with high initial WBC greater than 10,000/μl. (author)

  15. Monocytic leukemias.

    Science.gov (United States)

    Shaw, M T

    1980-05-01

    The monocytic leukemias may be subdivided into acute monocytic leukemia, acute myelomonocytic leukemia, and subacute and chronic myelomonocytic leukemia. The clinical features of acute monocytic and acute myelomonocytic leukemias are similar and are manifestations of bone marrow failure. Gingival hypertrophy and skin infiltration are more frequent in acute monocytic leukemia. Cytomorphologically the blast cells in acute monocytic leukemia may be undifferentiated or differentiated, whereas in the acute myelomonocytic variety there are mixed populations of monocytic and myeloblastic cells. Cytochemical characteristics include strongly positive reactions for nonspecific esterase, inhibited by fluoride. The functional characteristics of acute monocytic and acute myelomonocytic cells resemble those of monocytes and include glass adherence and phagocytoses, the presence of Fc receptors for IgG and C'3, and the production of colony stimulating activity. Subacute and chronic myelomonocytic leukemias are insidious and slowly progressive diseases characterized by anemia and peripheral blood monocytosis. Atypical monocytes called paramyeloid cells are characteristic. The drugs used in the treatment of acute monocytic and acute myelomonocytic leukemias include cytosine arabinoside, the anthracyclines, and VP 16-213. Drug therapy in subacute and chronic myelomonocytic leukemias is not usually indicated, although VP 16-213 has been claimed to be effective.

  16. Analysis of the risk of infection in patients with chronic lymphocytic leukemia in the era of novel therapies.

    Science.gov (United States)

    Williams, AnnaLynn M; Baran, Andrea M; Meacham, Philip J; Feldman, Megan M; Valencia, Hugo E; Newsom-Stewart, Catherine; Gupta, Nealansh; Janelsins, Michelle C; Barr, Paul M; Zent, Clive S

    2018-03-01

    We studied the risk of infections in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Major infections were defined as requiring hospital admission or intravenous antimicrobial treatment. Incidence rate (IR) ratios (IRR) were used to compare infection rates. Of 263 CLL patients followed for 936.9 person-years, 60% required treatment for progressive CLL (66 received ibrutinib). Infections occurred in 71.9% patients (IR 92.4/100 person-years) with 31.9% having major infections (IR 20.3/100 person-years) and infections causing 37.5% of deaths. CLL treatment was associated with significantly higher risk of major (IRR 3.31, 95% CI 2.10, 5.21) and minor (IRR 1.78, 95% CI 1.43, 2.22) infections. Compared to their previous chemoimmunotherapy patients receiving salvage ibrutinib therapy (n = 47) had a significantly increased risk of a major infection (IRR 2.35 95% CI 1.27, 4.34). The risk of infection in CLL patients remains high even with use of less immunosuppressive therapies.

  17. Family characteristics as risk factors for childhood acute lymphoblastic leukemia: a population-based case-control study.

    Directory of Open Access Journals (Sweden)

    Martin Feller

    Full Text Available BACKGROUND: To date, few risk factors for childhood acute lymphoblastic leukemia (ALL have been confirmed and the scientific literature is full of controversial "evidence." We examined if family characteristics, particularly maternal and paternal age and number of older siblings, were risk factors for childhood acute lymphoblastic leukemia (ALL. METHODOLOGY/PRINCIPAL FINDINGS: In this population-based nationwide matched case-control study, patients 0-14 years of age with ALL diagnosed 1991-2006 and registered in the Swiss Childhood Cancer Registry were linked with their census records of 1990 and 2000. Eight controls per case were selected from the census. The association between family characteristics and ALL was analyzed by conditional logistic regressions. We found that increasing maternal age was associated with incidence of ALL in the offspring (OR per 5-year increase in maternal age 1.18, 95% CI 1.05-1.31; p = 0.004, remaining stable (trend OR 1.14, 95% CI 0.99-1.31; p = 0.060 after adjustment for other risk factors. The association with paternal age was weaker (OR per 5-year increase 1.14, 95% CI 1.01-1.28, p = 0.032 and disappeared after adjustments. Number of older siblings was not associated with risk of ALL in the overall group of children aged 0-14 years at diagnosis. However, we found a negative trend between number of older siblings and ALL diagnosed at age 0-4 years (OR per sibling 0.85, 95% CI 0.68-1.06; p = 0.141 and a positive trend for ALL diagnosed at age 5-9 (OR 1.34, 95% CI 1.05-1.72; p = 0.019, with some evidence for an effect modification (p-value for interaction  = 0.040. CONCLUSIONS: As in other studies, increasing maternal, but not paternal age was associated with risk of ALL. We found only a weak association with the number of older siblings, suggesting a delay in disease manifestation rather than a decrease in incidence.

  18. Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome

    Science.gov (United States)

    2018-05-14

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; CD45-Positive Neoplastic Cells Present; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

  19. Treatment of chronic myeloid leukemia: assessing risk, monitoring response, and optimizing outcome.

    Science.gov (United States)

    Shanmuganathan, Naranie; Hiwase, Devendra Keshaorao; Ross, David Morrall

    2017-12-01

    Over the past two decades, tyrosine kinase inhibitors have become the foundation of chronic myeloid leukemia (CML) treatment. The choice between imatinib and newer tyrosine kinase inhibitors (TKIs) needs to be balanced against the known toxicity and efficacy data for each drug, the therapeutic goal being to maximize molecular response assessed by BCR-ABL RQ-PCR assay. There is accumulating evidence that the early achievement of molecular targets is a strong predictor of superior long-term outcomes. Early response assessment provides the opportunity to intervene early with the aim of ensuring an optimal response. Failure to achieve milestones or loss of response can have diverse causes. We describe how clinical and laboratory monitoring can be used to ensure that each patient is achieving an optimal response and, in patients who do not reach optimal response milestones, how the monitoring results can be used to detect resistance and understand its origins.

  20. 42 CFR 81.24 - Guidelines for leukemia.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Guidelines for leukemia. 81.24 Section 81.24 Public... Causation § 81.24 Guidelines for leukemia. (a) For claims involving leukemia, DOL will calculate one or more probability of causation estimates from up to three of the four alternate leukemia risk models included in...

  1. Improved treatment results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose cytarabine and mitoxantrone: results of Study Acute Myeloid Leukemia-Berlin-Frankfurt-Münster 93.

    Science.gov (United States)

    Creutzig, U; Ritter, J; Zimmermann, M; Reinhardt, D; Hermann, J; Berthold, F; Henze, G; Jürgens, H; Kabisch, H; Havers, W; Reiter, A; Kluba, U; Niggli, F; Gadner, H

    2001-05-15

    To improve outcome in high-risk patients, high-dose cytarabine and mitoxantrone (HAM) was introduced into the treatment of children with acute myelogenous leukemia (AML) in study AML-BFM 93. Patients were randomized to HAM as either the second or third therapy block, for the purpose of evaluation of efficacy and toxicity. A total of 471 children with de novo AML were entered onto the trial; 161 were at standard risk and 310 were at high risk. After the randomized induction (daunorubicin v idarubicin), further therapy, with the exception of HAM, was identical in the two risk groups and also comparable to that in study Acute Myeloid Leukemia-Berlin-Frankfurt-Münster (AML-BFM) 87. Overall, 387 (82%) of 471 patients achieved complete remission, and 5-year survival, event-free survival (EFS), and disease-free survival rates were 60%, 51%, and 62%, respectively. Idarubicin induction resulted in a significantly better blast cell reduction in the bone marrow on day 15. Estimated survival and probability of EFS were superior in study AML-BFM 93 compared with study AML-BFM 87 (P =.01, log-rank test). This improvement, however, was restricted to the 310 high-risk patients (remission rate and probability of 5-year EFS in study AML-BFM 93 v study AML-BFM 87: 78% v 68%, P =.007; and 44% v 31%, P =.01, log-rank test). Probability of 5-year EFS among standard-risk patients in study AML-BFM 93 was similar to that in study AML-BFM 87 (65% v 63%, P = not significant). Whether HAM was placed as the second or third therapy block was of minor importance. However, patients who received the less intensive daunorubicin treatment during induction benefited from early HAM. Improved treatment results in children with high-risk AML in study AML-BFM 93 must be attributed mainly to the introduction of HAM.

  2. Complementary and Alternative Medicine in the Pediatrics with Leukemia: A Narrative Review Study

    Directory of Open Access Journals (Sweden)

    Mojtaba Miladinia

    2017-01-01

    Full Text Available BackgroundFor using of complementary and alternative medicine methods (CAM in the leukemia pediatrics than other types of cancer, we have two great challenges; first challenge is their safety and risks and second challenge is study gaps in this field. Regarding to these challenges, this study is a narrative review of some CAM methods in the leukemia pediatrics from the perspective of their safety, risks and study gaps.Materials and MethodsIn this narrative review study searched both international electronic databases including ISI Web of science, PubMed, PsycINFO, CINAHL, ISC, Embase, Scopus, Google Scholar and also, Iranian electronic databases including Magiran, Medlib and SID. Also, searches were performed separately in the specialized journals in the field of leukemia pediatrics and complementary and alternative medicine research.ResultsMusic therapy, gentle yoga movements, gentle massage types are quite safe for leukemia pediatrics. But, use of heavy yoga movements, massages with deep pressure, acupressure and acupuncture can be dangerous for leukemia pediatrics (risks of bleeding and or infection. Also, this study showed that, the number of investigations about the use of CAM in the leukemia pediatrics is very limited; especially in the field of yoga and acupuncture.ConclusionThe results of this study can be a basis both for chose of safe CAM method in these children and a basis for future studies on the basis of identified study gaps in this review study.

  3. RISK MANAGEMENT IN THE ELECTRONIC BUSINESS

    Directory of Open Access Journals (Sweden)

    Georgeta Soava

    2016-12-01

    Full Text Available Risk should not be understood as a destructive phenomenon, but bear in mind that managers who know how to use it can lead to real opportunities. Manager must first recognize the existence of risk, namely to identify and then use specific methods to avoid or reduce the risk. The purpose of this paper is to enter the world, at all simple, of risk management, relatively easy concept to understand but not so easy to put into practice. Of course, the approach relates primarily at the risks inherent of the business in digital environments, but they not represent only a particular case of the risks they are exposed, in general, the companies. In the paper we put in evidence the significance in general business, risks in e-business, then we added a description of the types of security risks, an exemplification of these and a series of test scenarios, and finally to make a analysis of operational solutions of risk management

  4. Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group.

    Science.gov (United States)

    Oriol, Albert; Vives, Susana; Hernández-Rivas, Jesús-María; Tormo, Mar; Heras, Inmaculada; Rivas, Concepción; Bethencourt, Concepción; Moscardó, Federico; Bueno, Javier; Grande, Carlos; del Potro, Eloy; Guardia, Ramon; Brunet, Salut; Bergua, Juan; Bernal, Teresa; Moreno, Maria-José; Calvo, Carlota; Bastida, Pilar; Feliu, Evarist; Ribera, Josep-Maria

    2010-04-01

    About one half of adults with acute lymphoblastic leukemia are not cured of the disease and ultimately die. The objective of this study was to explore the factors influencing the outcome of adult patients with relapsed acute lymphoblastic leukemia. We analyzed the characteristics, the outcome and the prognostic factors for survival after first relapse in a series of 263 adult patients with acute lymphoblastic leukemia (excluding those with mature B-cell acute lymphoblastic leukemia) prospectively enrolled in four consecutive risk-adapted PETHEMA trials. The median overall survival after relapse was 4.5 months (95% CI, 4-5 months) with a 5-year overall survival of 10% (95% CI, 8%-12%); 45% of patients receiving intensive second-line treatment achieved a second complete remission and 22% (95% CI, 14%-30%) of them remained disease free at 5 years. Factors predicting a good outcome after rescue therapy were age less than 30 years (2-year overall survival of 21% versus 10% for those over 30 years old; P<0.022) and a first remission lasting more than 2 years (2-year overall survival of 36% versus 17% among those with a shorter first remission; P<0.001). Patients under 30 years old whose first complete remission lasted longer than 2 years had a 5-year overall survival of 38% (95% CI, 23%-53%) and a 5-year disease-free survival of 53% (95% CI, 34%-72%). The prognosis of adult patients with acute lymphoblastic leukemia who relapse is poor. Those aged less than 30 years with a first complete remission lasting longer than 2 years have reasonable possibilities of becoming long-term survivors while patients over this age or those who relapse early cannot be successfully rescued using the therapies currently available.

  5. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways.

    Science.gov (United States)

    Guerenne, Laura; Beurlet, Stéphanie; Said, Mohamed; Gorombei, Petra; Le Pogam, Carole; Guidez, Fabien; de la Grange, Pierre; Omidvar, Nader; Vanneaux, Valérie; Mills, Ken; Mufti, Ghulam J; Sarda-Mantel, Laure; Noguera, Maria Elena; Pla, Marika; Fenaux, Pierre; Padua, Rose Ann; Chomienne, Christine; Krief, Patricia

    2016-01-27

    In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS) patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

  6. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways

    Directory of Open Access Journals (Sweden)

    Laura Guerenne

    2016-01-01

    Full Text Available Abstract Background In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. Methods We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS and acute myeloid leukemia (AML post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Results Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. Conclusions These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

  7. Juvenile Myelomonocytic Leukemia

    Science.gov (United States)

    ... myeloproliferative neoplasms, leukemia , and other conditions . Chronic Myelomonocytic Leukemia Key Points Chronic myelomonocytic leukemia is a disease ... chance of recovery) and treatment options. Chronic myelomonocytic leukemia is a disease in which too many myelocytes ...

  8. Atypical Chronic Myelogenous Leukemia

    Science.gov (United States)

    ... myeloproliferative neoplasms, leukemia , and other conditions . Chronic Myelomonocytic Leukemia Key Points Chronic myelomonocytic leukemia is a disease ... chance of recovery) and treatment options. Chronic myelomonocytic leukemia is a disease in which too many myelocytes ...

  9. Is the excess risk of childhood leukemia at Sellafield consistent with the experiences of A-bomb survivors in Hiroshima and Nagasaki ?

    International Nuclear Information System (INIS)

    Yoshimoto, Yasuhiko

    1991-01-01

    The purpose of this communication is to summarize briefly selected studies relevant to the difference between the apparent pre-conception radiation-associated leukemia risks in the offspring born in the area near the Sellafield plant and to the atomic bomb survivors. Although no doubt exists about the hypothesis that radiation damages the genetic material in reproductive cells, it is important to recognize how small the effect in the first generation would be based on the various genetic endpoints. Generally only a small fraction of leukemia cases are inherited -- the proportion among all spontaneous cases does not exceed 10 %. Because there is still uncertainty and controversy about the genetic effects of radiation, the possible complex confounding factors are also briefly mentioned. It is clear that the studies of the atomic bomb survivors are pertinent to the possible genetic effect due to radiation-induced mutations in the spermatogonia and oocytes while the observations in Sellafield are, as suggested by Gardner et al. pertinent to the in post-meiotic stages of spermatogenesis. No significant effect of atomic bomb radiation can be shown on the risk of leukemia as well as other genetic effect endpoints, such as the frequency of mutations associated with specific proteins, cytogenetic abnormalities, survival, and so on. (author)

  10. Protracted Administration of L-Asparaginase in Maintenance Phase Is the Risk Factor for Hyperglycemia in Older Patients with Pediatric Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Yoshida, Hideki; Imamura, Toshihiko; Saito, Akiko M.; Takahashi, Yoshihiro; Suenobu, So-ichi; Hasegawa, Daiichiro; Deguchi, Takao; Hashii, Yoshiko; Kawasaki, Hirohide; Endo, Mikiya; Hori, Hiroki; Suzuki, Nobuhiro; Kosaka, Yoshiyuki; Kato, Koji; Yumura-Yagi, Keiko; Hara, Junichi; Oda, Megumi; Sato, Atsushi; Horibe, Keizo

    2015-01-01

    Although L-asparaginase related hyperglycemia is well known adverse event, it is not studied whether the profile of this adverse event is affected by intensification of L-asparaginase administration. Here, we analyzed the profile of L-asparaginase related hyperglycemia in a 1,176 patients with pediatric acute lymphoblastic leukemia treated according to the Japan Association of Childhood Leukemia Study ALL-02 protocol using protracted L-asparaginase administration in maintenance phase. We determined that a total of 75 L-asparaginase related hyperglycemia events occurred in 69 patients. Although 17 events (17/1176, 1.4%) developed in induction phase, which was lower incidence than those (10–15%) in previous reports, 45 events developed during the maintenance phase with protracted L-asparaginase administration. Multivariate analysis showed that older age at onset (≥10 years) was a sole independent risk factor for L-asparaginase-related hyperglycemia (Phyperglycemia. These findings suggest that protracted administration of L-asparaginase is the risk factor for hyperglycemia when treating adolescent and young adult acute lymphoblastic leukemia patients. PMID:26317422

  11. Haploidentical hematopoietic stem cell transplant with umbilical cord-derived multipotent mesenchymal cell infusion for the treatment of high-risk acute leukemia in children.

    Science.gov (United States)

    Zhu, Ling; Wang, Zhidong; Zheng, Xiaoli; Ding, Li; Han, Dongmei; Yan, Hongmin; Guo, Zikuan; Wang, Hengxiang

    2015-05-01

    In this study, 25 children with high-risk acute leukemia received haploidentical hematopoietic stem cell transplant (haplo-HSCT) with co-transfusion of umbilical cord multipotent mesenchymal cells (UC-MSCs). Adverse effects, hematopoietic recovery, complications and outcome were observed during a median follow-up of 12.8 months (range: 3-25 months). Myeloid engraftment was rapid, and the median time to neutrophil and platelet recovery was 15.12 days and 20.08 days, respectively. Eight patients developed grade I skin acute graft-versus-host disease (aGVHD) that responded well to standard steroid therapy. Of note, cytomegalovirus viremia was observed in most patients (23/25 cases). Patients died mainly of leukemia relapse and pulmonary complication. Fourteen patients are currently alive and remain with full donor chimerism at the time of reporting. The present results suggest further clinical trials to testify the effectiveness of UC-MSCs to prevent aGVHD in haplo-HSCT for treating children with high-risk leukemia.

  12. Translational Phase I Trial of Vorinostat (Suberoylanilide Hydroxamic Acid) Combined with Cytarabine and Etoposide in Patients with Relapsed, Refractory, or High-Risk Acute Myeloid Leukemia

    Science.gov (United States)

    Gojo, Ivana; Tan, Ming; Fang, Hong-Bin; Sadowska, Mariola; Lapidus, Rena; Baer, Maria R.; Carrier, France; Beumer, Jan H.; Anyang, Bean N.; Srivastava, Rakesh K.; Espinoza-Delgado, Igor; Ross, Douglas D.

    2015-01-01

    Purpose To determine the maximum-tolerated dose (MTD) of the histone deacetylase inhibitor vorinostat combined with fixed doses of cytarabine (ara-C or cytosine arabinoside) and etoposide in patients with poor-risk or advanced acute leukemia, to obtain preliminary efficacy data, describe pharmacokinetics, and in vivo pharmacodynamic effects of vorinostat in leukemia blasts. Experimental Design In this open-label phase I study, vorinostat was given orally on days one to seven at three escalating dose levels: 200 mg twice a day, 200 mg three times a day, and 300 mg twice a day. On days 11 to 14, etoposide (100 mg/m2) and cytarabine (1 or 2 g/m2 twice a day if ≥65 or vorinostat 200 mg twice a day. Of 21 patients enrolled, seven attained a complete remission (CR) or CR with incomplete platelet recovery, including six of 13 patients treated at the MTD. The median remission duration was seven months. No differences in percentage S-phase cells or multidrug resistance transporter (MDR1 or BCRP) expression or function were observed in vivo in leukemia blasts upon vorinostat treatment. Conclusions Vorinostat 200 mg twice a day can be given safely for seven days before treatment with cytarabine and etoposide. The relatively high CR rate seen at the MTD in this poor-risk group of patients with AML warrants further studies to confirm these findings. PMID:23403629

  13. Birth characteristics, maternal reproductive history, and the risk of infant leukemia: a report from the Children's Oncology Group.

    Science.gov (United States)

    Spector, Logan G; Davies, Stella M; Robison, Leslie L; Hilden, Joanne M; Roesler, Michelle; Ross, Julie A

    2007-01-01

    Leukemias with MLL gene rearrangements predominate in infants (birth weight, higher birth order, and prior fetal loss have, with varying consistency, been associated with infant leukemia, but no studies have reported results with respect to MLL status. Here, we report for the first time such an analysis. During 1999 to 2003, mothers of 240 incident cases (113 MLL(+), 80 MLL(-), and 47 indeterminate) and 255 random digit dialed controls completed a telephone interview. Odds ratios and 95% confidence intervals for quartile of birth weight, birth order, gestational age, maternal age at delivery, prior fetal loss, pre-pregnancy body mass index, and weight gain during pregnancy were obtained using unconditional logistic regression; P for linear trend was obtained by modeling continuous variables. There was a borderline significant linear trend of increasing birth weight with MLL(+) (P = 0.06), but not MLL(-) (P = 0.93), infant leukemia. Increasing birth order showed a significant inverse linear trend, independent of birth weight, with MLL(+) (P = 0.01), but not MLL(-) (P = 0.18), infant leukemia. Other variables of interest were not notably associated with infant leukemia regardless of MLL status. This investigation further supports the contention that molecularly defined subtypes of infant leukemia have separate etiologies.

  14. Understanding Leukemia

    Science.gov (United States)

    ... for as long as they take it. Allogeneic stem cell transplantation is another treatment option that is only done if CML is not responding as expected to drug therapy. Chronic Lymphocytic Leukemia (CLL) . Some CLL patients do not need treatment ...

  15. Perceived risk and trust associated with purchasing at Electronic Marketplaces

    NARCIS (Netherlands)

    Meents, Selmar; Tan, Yao-Hua; Verhagen, Tibert

    2006-01-01

    Understanding consumer behaviour is of vital importance to consumer oriented e-business models today. In this paper we study the relationships between consumer perceptions of risk and trust and the attitude towards purchasing at a consumer-to-consumer electronic marketplace. Typical for electronic

  16. Fragment length analysis screening for detection of CEBPA mutations in intermediate-risk karyotype acute myeloid leukemia.

    Science.gov (United States)

    Fuster, Oscar; Barragán, Eva; Bolufer, Pascual; Such, Esperanza; Valencia, Ana; Ibáñez, Mariam; Dolz, Sandra; de Juan, Inmaculada; Jiménez, Antonio; Gómez, Maria Teresa; Buño, Ismael; Martínez, Joaquín; Cervera, José; Montesinos, Pau; Moscardó, Federico; Sanz, Miguel Ángel

    2012-01-01

    During last years, molecular markers have been increased as prognostic factors routinely screened in acute myeloid leukemia (AML). Recently, an increasing interest has been reported in introducing to clinical practice screening for mutations in the CCAAT/enhancer-binding protein α (CEBPA) gene in AML, as it seems to be a good prognostic factor. However, there is no reliable established method for assessing CEBPA mutations during the diagnostic work-up of AMLs. We describe here a straightforward and reliable fragment analysis method based in PCR capillary electrophoresis (PCR-CE) for screening of CEBPA mutations; moreover, we present the results obtained in 151 intermediate-risk karyotype AML patients (aged 16-80 years). The method gave a specificity of 100% and sensitivity of 93% with a lower detection limit of 1-5% for CEBPA mutations. The series found 19 mutations and four polymorphisms in 12 patients, seven of whom (58%) presented two mutations. The overall frequency of CEBPA mutations in AML was 8% (n = 12). CEBPA mutations showed no coincidence with FLT3-ITD or NPM1 mutations. CEBPA mutation predicted better disease-free survival in the group of patients without FLT3-ITD, NPM, or both genes mutated (HR 3.6, IC 95%; 1.0-13.2, p = 0.05) and better overall survival in patients younger than 65 of this group without molecular markers (HR 4.0, IC 95%; 1.0-17.4, p = 0.05). In conclusion, the fragment analysis method based in PCR-CE is a rapid, specific, and sensitive method for CEBPA mutation screening and our results confirm that CEBPA mutations can identify a subgroup of patients with favorable prognosis in AML with intermediate-risk karyotype.

  17. The -137G/C Polymorphism in Interleukin-18 Gene Promoter Contributes to Chronic Lymphocytic and Chronic Myelogenous Leukemia Risk in Turkish Patients

    Directory of Open Access Journals (Sweden)

    Serap Yalçın

    2015-12-01

    Full Text Available Objective: Interleukin-18 (IL-18 is a cytokine that belongs to the IL-1 superfamily and is secreted by various immune and nonimmune cells. Evidence has shown that IL-18 has both anticancer and procancer effects. The aim of this study was to evaluate the relationship between IL-18 gene polymorphisms and susceptibility to chronic lymphocytic leukemias (CLL and chronic myelogenous leukemias (CML in Turkish patients. Materials and Methods: The frequencies of polymorphisms (rs61667799(G/T, rs5744227(C/G, rs5744228(A/G, and rs187238(G/C were studied in 20 CLL patients, 30 CML patients, and 30 healthy individuals. The genotyping was performed by polymerase chain reaction and DNA sequencing analysis. Results: Significant associations were detected between the IL-18 rs187238(G/C polymorphism and chronic leukemia. A higher prevalence of the C allele was found in CML cases with respect to controls. The GC heterozygous and CC homozygous genotypes were associated with risk of CML when compared with controls. However, prevalence of the C allele was not significantly high in CLL cases with respect to controls. There was only a significant difference between the homozygous CC genotype of CLL patients and the control group; thus, it can be concluded that the CC genotype may be associated with the risk of CLL. Based on our data, there were no significant associations between the IL-18 rs61667799(G/T, rs5744227(C/G, or rs5744228(A/G polymorphisms and CLL or CML. Conclusions: IL-18 gene promoter rs187238(G/C polymorphism is associated with chronic leukemia in the Turkish population. However, due to the limited number of studied patients, these are preliminary results that show the association between -137G/C polymorphism and patients (CLL and CML. Further large-scale studies combined with haplotype and expression analysis are required to validate the current findings.

  18. Comparative analysis of unrelated cord blood transplantation and HLA-matched sibling hematopoietic stem cell transplantation in children with high-risk or advanced acute leukemia.

    Science.gov (United States)

    Zheng, Changcheng; Zhu, Xiaoyu; Tang, Baolin; Yao, Wen; Song, Kaidi; Tong, Juan; Geng, Liangquan; Liu, Huilan; Sun, Zimin

    2015-03-01

    The aim of this report was to present a clinical comparison of unrelated cord blood transplantation (CBT) and human leukocyte antigen (HLA)-matched sibling allogeneic peripheral blood stem cell or bone marrow transplantation (allo-PBSCT/BMT) in children with high-risk or advanced acute leukemia. A total of 115 consecutive pediatric patients received unrelated CBT (n = 90) or sibling allo-PBSCT/BMT (n = 25) between 2000 and 2012. Neutrophil and platelet recovery were significantly delayed after CBT compared to allo-PBSCT/BMT. There was no difference in the incidence of acute graft-versus-host disease (GVHD) or chronic GVHD between the two groups. The cumulative incidence of transplant-related mortality (TRM) was higher in the CBT group than in the allo-PBSCT/BMT group (32.5 vs 12.8 %) (p = 0.03). The cumulative incidence of relapse was 13.1 % after CBT, which was significantly lower than that of after allo-PBSCT/BMT (45.3 %) (p = 0.015). The overall survival (OS) and leukemia-free survival (LFS) in the CBT group were similar to those of the allo-PBSCT/BMT group; however, for acute myeloid leukemia (AML) patients, the 5-year LFS in the CBT group was slightly better than the allo-PBSCT/BMT group (55.7 % for CBT and 32.7 % for allo-PBSCT/BMT) (p = 0.08). Our comparisons suggest that for high-risk or advanced childhood acute leukemia, unrelated CBT has a higher TRM and similar long-term survival, but better antileukemia effect than HLA-matched sibling PBSCT/BMT. New strategies and better supportive care are required to decrease the TRM of CBT.

  19. PDGFRα promoter polymorphisms and expression patterns influence risk of development of imatinib-induced thrombocytopenia in chronic myeloid leukemia: A study from India.

    Science.gov (United States)

    Guru, Sameer Ahmad; Mir, Rashid; Bhat, Musadiq; Najar, Imtiyaz; Zuberi, Mariyam; Sumi, Mamta; Masroor, Mirza; Gupta, Naresh; Saxena, Alpana

    2017-10-01

    myeloid leukemia patient groups (p chronic myeloid leukemia patients were associated with an increased risk of developing thrombocytopenia, with odds ratios 6.5 (95% confidence interval = 2.02-0.89, p = 0.001) and 6.0 (95% confidence interval = 2.26-15.91, p = 0.0002), respectively. Similarly, -909C/A promoter polymorphism genotype distribution also differed significantly between thrombocytopenic and non-thrombocytopenic chronic myeloid leukemia patient groups (p = 0.02), and a significantly increased risk of imatinib-induced thrombocytopenia was associated with -909C/A polymorphism mutant homozygous (AA) genotypes the odds ratio being 7.7 (95% confidence interval 1.50 to 39.91, p = 0.009). However, no significant risk of imatinib-induced thrombocytopenia was found to be associated with heterozygous genotype (-909C/A) with odds ratio 1.9 (95% confidence interval = 0.86-4.56, p = 1.14). Platelet-derived growth factor receptor-α messenger RNA expression was significantly higher in chronic myeloid leukemia patients compared to controls (p = 0.008). Moreover, patients with imatinib-induced thrombocytopenia had a significantly lower platelet-derived growth factor receptor-α messenger RNA expression, compared to patients without thrombocytopenia (p = 0.01). A differential expression of platelet-derived growth factor receptor-α messenger RNA was observed with respect to different +68 GA ins/del and -909C/A polymorphism genotypes. The +68GA deletion allele and -909A allele were significantly associated with lower expression of platelet-derived growth factor receptor-α messenger RNA. The platelet-derived growth factor receptor-α +68GA del/del, +68GA ins/del, and -909AA genotypes are associated with an increased risk of developing thrombocytopenia in imatinib-treated chronic myeloid leukemia patients. A significantly lower platelet-derived growth factor receptor-α messenger RNA expression accompanies the +68GA deletion allele in an

  20. Genetic polymorphisms associated to folate transport as predictors of increased risk for acute lymphoblastic leukemia in Mexican children

    Directory of Open Access Journals (Sweden)

    Fausto Zaruma-Torres

    2016-08-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a frequent neoplasia occurring in children. The most commonly used drug for the treatment of ALL is methotrexate (MTX, an anti-folate agent. Previous studies suggest that folate transporters play a role in ALL prognosis and that genetic polymorphism of genes encoding folate transporters may increase the risk of ALL. Therefore, the main goal of this study was to determine the associations among six genetic polymorphisms in four genes related with the folate transporter pathway to determine a relationship with the occurrence of ALL in Mexican children.A case-control study was performed in 73 ALL children and 133 healthy children from Northern and Northwestern Mexico. COL18A1 (rs2274808, SLC19A1 (rs2838956, ABCB1 (rs1045642 and rs1128503 and ABCC5 (rs9838667 and rs3792585. polymorphisms were assayed through qPCR.Our results showed an increased ALL risk in children carrying CT genotype (OR=2.55, CI 95% 1.11-5.83, p=0.0001 and TT genotype (OR=21.05, CI 95% 5.62-78.87, p<0.0001 of COL18A1 rs2274808; in SLC19A1 rs2838956 AG carriers (OR=44.69, CI 95% 10.42-191.63, p=0.0001; in ABCB1 rs1045642 TT carriers (OR=13.76, CI 95% 5.94-31.88, p=0.0001; in ABCC5 rs9838667 AC carriers (OR=2.61, CI 95% 1.05-6.48, p<0.05; and in ABCC5 rs3792585 CC carriers (OR=9.99, CI 95% 3.19-31.28, p=0.004. Moreover, several combinations of genetic polymorphisms were found to be significantly associated with a risk for ALL. Finally, two combinations of ABCC5 polymorphisms resulted in protection from this neoplasia.In conclusion, certain genetic polymorphisms related to the folate transport pathway, particularly COL18A1 rs2274808, SLC19A1 rs2838956, ABCB1 rs1045642 and ABCC5 rs3792585, were associated with an increased risk for ALL in Mexican children.

  1. Socioeconomic status (SES) and childhood acute myeloid leukemia (AML) mortality risk: Analysis of SEER data.

    Science.gov (United States)

    Knoble, Naomi B; Alderfer, Melissa A; Hossain, Md Jobayer

    2016-10-01

    Socioeconomic status (SES) is a complex construct of multiple indicators, known to impact cancer outcomes, but has not been adequately examined among pediatric AML patients. This study aimed to identify the patterns of co-occurrence of multiple community-level SES indicators and to explore associations between various patterns of these indicators and pediatric AML mortality risk. A nationally representative US sample of 3651 pediatric AML patients, aged 0-19 years at diagnosis was drawn from 17 Surveillance, Epidemiology, and End Results (SEER) database registries created between 1973 and 2012. Factor analysis, cluster analysis, stratified univariable and multivariable Cox proportional hazards models were used. Four SES factors accounting for 87% of the variance in SES indicators were identified: F1) economic/educational disadvantage, less immigration; F2) immigration-related features (foreign-born, language-isolation, crowding), less mobility; F3) housing instability; and, F4) absence of moving. F1 and F3 showed elevated risk of mortality, adjusted hazards ratios (aHR) (95% CI): 1.07(1.02-1.12) and 1.05(1.00-1.10), respectively. Seven SES-defined cluster groups were identified. Cluster 1 (low economic/educational disadvantage, few immigration-related features, and residential-stability) showed the minimum risk of mortality. Compared to Cluster 1, Cluster 3 (high economic/educational disadvantage, high-mobility) and Cluster 6 (moderately-high economic/educational disadvantages, housing-instability and immigration-related features) exhibited substantially greater risk of mortality, aHR(95% CI)=1.19(1.0-1.4) and 1.23 (1.1-1.5), respectively. Factors of correlated SES-indicators and their pattern-based groups demonstrated differential risks in the pediatric AML mortality indicating the need of special public-health attention in areas with economic-educational disadvantages, housing-instability and immigration-related features. Copyright © 2016 Elsevier Ltd. All

  2. Insecticide exposure and farm history in relation to risk of lymphomas and leukemias in the Women's Health Initiative observational study cohort.

    Science.gov (United States)

    Schinasi, Leah H; De Roos, Anneclaire J; Ray, Roberta M; Edlefsen, Kerstin L; Parks, Christine G; Howard, Barbara V; Meliker, Jaymie R; Bonner, Matthew R; Wallace, Robert B; LaCroix, Andrea Z

    2015-11-01

    Relationships of farm history and insecticide exposure at home or work with lymphohematopoietic (LH) neoplasm risk were investigated in a large prospective cohort of US women. In questionnaires, women self-reported history living or working on a farm, personally mixing or applying insecticides, insecticide application in the home or workplace by a commercial service, and treating pets with insecticides. Relationships with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, plasma cell neoplasms, and myeloid leukemia were investigated using Cox proportional hazard models. Age and farming history were explored as effect modifiers. The analysis included 76,493 women and 822 NHL cases. Women who ever lived or worked on a farm had 1.12 times the risk of NHL (95% confidence interval [CI] = 0.95-1.32) compared to those who did not. Women who reported that a commercial service ever applied insecticides in their immediate surroundings had 65% higher risk of CLL/SLL (95% CI = 1.15-2.38). Women aged less than 65 years who ever applied insecticides had 87% higher risk of DLBCL (95% CI = 1.13-3.09). Insecticide exposures may contribute to risk of CLL/SLL and DLBCL. Future studies should examine relationships of LH subtypes with specific types of household insecticides. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Insecticide exposure and farm history in relation to risk of lymphomas and leukemias in the Women’s Health Initiative (WHI) observational study cohort

    Science.gov (United States)

    Schinasi, L; De Roos, AJ; Ray, RM; Edlefsen, KL; Parks, CG; Howard, BV; Meliker; Bonner, MR; Wallace, RB; LaCroix, AZ

    2017-01-01

    Purpose Relationships of farm history and insecticide exposure at home or work with lymphohematopoietic (LH) neoplasm risk were investigated in a large prospective cohort of United States women. Methods In questionnaires, women self-reported history living or working on a farm, personally mixing or applying insecticides, insecticide application in the home or workplace by a commercial service, and treating pets with insecticides. Relationships with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, plasma cell neoplasms, and myeloid leukemia were investigated using Cox proportional hazard models. Age and farming history were explored as effect modifiers. Results The analysis included 76,493 women and 822 NHL cases. Women who ever lived or worked on a farm had 1.12 times the risk of NHL (95% CI: 0.95–1.32) compared to those who did not. Women who reported that a commercial service ever applied insecticides in their immediate surroundings had 65% higher risk of CLL/SLL (95% CI: 1.15–2.38). Women younger than 65 who ever applied insecticides had 87% higher risk of DLBCL (95% CI: 1.13–3.09). Conclusions Insecticide exposures may contribute to risk of CLL/SLL and DLBCL. Future studies should examine relationships of LH subtypes with specific types of household insecticides. PMID:26365305

  4. Infection and childhood leukemia: review of evidence

    Directory of Open Access Journals (Sweden)

    Raquel da Rocha Paiva Maia

    2013-12-01

    Full Text Available OBJECTIVE : To analyze studies that evaluated the role of infections as well as indirect measures of exposure to infection in the risk of childhood leukemia, particularly acute lymphoblastic leukemia. METHODS : A search in Medline, Lilacs, and SciELO scientific publication databases initially using the descriptors “childhood leukemia” and “infection” and later searching for the words “childhood leukemia” and “maternal infection or disease” or “breastfeeding” or “daycare attendance” or “vaccination” resulted in 62 publications that met the following inclusion criteria: subject aged ≤ 15 years; specific analysis of cases diagnosed with acute lymphoblastic leukemia or total leukemia; exposure assessment of mothers’ or infants’ to infections (or proxy of infection, and risk of leukemia. RESULTS : Overall, 23 studies that assessed infections in children support the hypothesis that occurrence of infection during early childhood reduces the risk of leukemia, but there are disagreements within and between studies. The evaluation of exposure to infection by indirect measures showed evidence of reduced risk of leukemia associated mainly with daycare attendance. More than 50.0% of the 16 studies that assessed maternal exposure to infection observed increased risk of leukemia associated with episodes of influenza, pneumonia, chickenpox, herpes zoster, lower genital tract infection, skin disease, sexually transmitted diseases, Epstein-Barr virus, and Helicobacter pylori . CONCLUSIONS : Although no specific infectious agent has been identified, scientific evidence suggests that exposure to infections has some effect on childhood leukemia etiology.

  5. Serum galactomannan screening for diagnosis of invasive pulmonary aspergillosis in children after stem cell transplantation or with high-risk leukemia.

    Science.gov (United States)

    Gefen, Aharon; Zaidman, Irina; Shachor-Meyouhas, Yael; Avidor, Israela; Hakim, Fahed; Weyl Ben-Arush, Myriam; Kassis, Imad

    2015-03-01

    Both transplanted and leukemia patients are at high risk (HR) for invasive pulmonary aspergillosis (IPA). Methods for rapid diagnosis are crucial. Our objective was to investigate the impact of serial serum galactomannan assay (GMA) screening on IPA diagnosis in children. Between January 2010 and December 2011, all children following stem cell transplantation (SCT) or with HR leukemia were prospectively included. Serum samples for GMA were taken once-twice weekly. Results >.5 were considered positive. Patients suspected of having IPA were stratified as possible, probable, and definite. Forty-six children (median age, 8 years) were included, 38 after SCT (32 allogeneic), 8 with HR leukemia. A total of 510 samples were taken; screening period was 1-6 months for 34 patients. GMA was negative in 28 patients, all but one without suspicion of IPA. Eighteen patients had positive GMA: while four (22%) were upgraded to probable IPA, fourteen (78%) were considered as false positives (FP), some associated with piperacillin-tazobactam treatment. GMA sensitivity and specificity were 0.8 and 0.66, respectively; positive- and negative-predictive values (PPV, NPV) were 0.22 and 0.96, respectively. GMA may have a role in evaluating HR children for IPA. Both NPV and FP rates are high. The cost benefit of early detection versus over-diagnosis should be further studied.

  6. Do We Know What Causes Chronic Myeloid Leukemia?

    Science.gov (United States)

    ... Be Prevented? More In Chronic Myeloid Leukemia About Chronic Myeloid Leukemia Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To Top Imagine a world ...

  7. Treatment-associated leukemia following testicular cancer

    NARCIS (Netherlands)

    Travis, LB; Andersson, M; Gospodarowicz, M; van Leeuwen, FE; Bergfeldt, K; Lynch, CF; Curtis, RE; Kohler, BA; Wiklund, T; Storm, H; Holowaty, E; Hall, P; Pukkala, E; Sleijfer, DT; Clarke, EA; Boice, JD; Stovall, M; Gilbert, E

    2000-01-01

    Background: Men with testicular cancer are at an increased risk of leukemia, but the relationship to prior treatments is not well characterized. The purpose of our study was to describe the risk of leukemia following radiotherapy and chemotherapy for testicular cancer. Methods: Within a

  8. Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC).

    Science.gov (United States)

    Marcotte, Erin L; Thomopoulos, Thomas P; Infante-Rivard, Claire; Clavel, Jacqueline; Petridou, Eleni Th; Schüz, Joachim; Ezzat, Sameera; Dockerty, John D; Metayer, Catherine; Magnani, Corrado; Scheurer, Michael E; Mueller, Beth A; Mora, Ana M; Wesseling, Catharina; Skalkidou, Alkistis; Rashed, Wafaa M; Francis, Stephen S; Ajrouche, Roula; Erdmann, Friederike; Orsi, Laurent; Spector, Logan G

    2016-04-01

    Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery. We pooled data from 13 case-control studies from the Childhood Leukemia International Consortium done in nine countries (Canada, Costa Rica, Egypt, France, Germany, Greece, Italy, New Zealand, and the USA) for births from 1970-2013. We analysed caesarean delivery overall and by indications that probably resulted in prelabour caesarean delivery or emergency caesarean delivery. We used multivariable logistic regression models, adjusted for child's birthweight, sex, age, ethnic origin, parental education, maternal age, and study, to estimate odds ratios (ORs) and 95% CIs for the risk of ALL and acute myeloid leukaemia (AML) in children aged 0-14 years at diagnosis. The studies provided data for 8780 ALL cases, 1332 AML cases, and 23 459 controls, of which the birth delivery method was known for 8655 (99%) ALL cases, 1292 (97%) AML cases, and 23 351 (>99%) controls. Indications for caesarean delivery were available in four studies (there were caesarean deliveries for 1061 of 4313 ALL cases, 138 of 664 AML cases, and 1401 of 5884 controls). The OR for all indications of caesarean delivery and ALL was 1·06 (95% CI 0·99-1·13), and was significant for prelabour caesarean delivery and ALL (1·23 [1·04-1·47]; p=0·018). Emergency caesarean delivery was not associated with ALL (OR 1·02 [95% CI 0·81-1·30]). AML was not associated with caesarean delivery (all indications OR 0·99 [95% CI 0·84-1·17]; prelabour caesarean delivery 0·83 [0·54-1·26]; and emergency caesarean delivery 1·05 [0·63-1·77]). Our results suggest an increased risk of

  9. Polymorphism of XRCC1, XRCC3, and XPD Genes and Risk of Chronic Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Claudia Bănescu

    2014-01-01

    Full Text Available The genetic polymorphisms of X-ray repair cross complementing group 1 (XRCC1, X-ray repair cross complementing group 3 (XRCC3, and xeroderma pigmentosum complementation group D (XPD repair genes may lead to genetic instability and leukemogenesis. The purpose of the study was to evaluate the association between XRCC1 Arg399Gln, Arg280His and Arg194Trp, XRCC3 Thr241Met, and XPD Lys751Gln polymorphisms and the risk of developing CML in Romanian patients. A total of 156 patients diagnosed with CML and 180 healthy controls were included in this study. We found no association between CML and XRCC1 or XRCC3 variant genotypes in any of the investigated cases. A significant difference was observed in the variant genotype frequencies of the XPD Lys751Gln polymorphism between the patients with CML and control group (for variant homozygous genotypes, OR=2.37; 95% CI=1.20–4.67; P value = 0.016 and for combined heterozygous and variant homozygous genotypes, OR=1.72; 95% CI=1.10–2.69; P value = 0.019. This was also observed when analyzing the variant 751Gln allele (OR=1.54; 95% CI=1.13–2.11; P value = 0.008. Our results suggest that the XPD Lys751Gln variant genotype increases the risk of CML.

  10. Leukemia, multiple myeloma, and malignant lymphoma

    International Nuclear Information System (INIS)

    Ichimaru, M.; Ishimaru, T.; Ohkita, T.

    1986-01-01

    Excess risk of leukemia among atomic bomb (A-bomb) survivors increased with radiation dose in Hiroshima and Nagasaki. The incidence of all types of leukemia, except chronic lymphocytic leukemia, has increased among A-bomb survivors. However, chronic myelogenous leukemia (CML) is thought to be the most characteristic type of the A-bomb induced leukemias. The highest risk of leukemia among A-bomb survivors was recognized in 1951 and has not yet disappeared in survivors in Hiroshima. Excess risk of leukemia in the younger age at time of bomb (ATB) groups appeared early; however, in older age ATB groups it appeared much later especially among Hiroshima survivors. In both cities the effect of radiation exposure on the occurrence of CML was more clearly observable in the younger age ATB groups and occurred more frequently in Hiroshima. Leukemia among individuals exposed in utero and children of A-bomb survivors has not increased significantly. The relationship between radiation induced leukemia and chromosome abnormalities is discussed. Twenty years after the A-bomb, the risk of multiple myeloma (MM) increased among survivors aged 20-59 years ATB. Non-Hodgkin's malignant lymphoma also increased among A-bomb survivors and showed roughly the same tendency as MM

  11. Leukemia, multiple myeloma, and malignant lymphoma

    International Nuclear Information System (INIS)

    Ichimaru, Michito; Ohkita, Takeshi; Ishimaru, Toranosuke.

    1986-01-01

    Excess risk of leukemia among atomic bomb (A-bomb) survivors increased with radiation dose in Hiroshima and Nagasaki. The incidence of all types of leukemia, except chronic lymphocytic leukemia, has increased among A-bomb survivors. However, chronic myelogenous leukemia (CML) is thought to be the most characteristic type of the A-bomb induced leukemias. The highest risk of leukemia among A-bomb survivors was recognized in 1951 and has not yet disappeared in survivors in Hiroshima. Excess risk of leukemia in the younger age at time of bomb (ATB) groups appeared early; however, in the older age ATB groups it appeared much later especially among Hiroshima survivors. In both cities the effect of radiation exposure on the occurrence of CML was more clearly observable in the younger age ATB groups and occurred more frequently in Hiroshima. Leukemia among individuals exposed in utero and children of A-bomb survivors has not increased significantly. The relationship between radiation induced leukemia and chromosome abnormalities is discussed. Twenty years after the A-bomb, the risk of multiple myeloma (MM) increased among survivors aged 20 - 59 years ATB. Non-Hodgkin's malignant lymphoma also increased among A-bomb survivors and showed roughly the same tendency as MM. (author)

  12. Parental Exposure to Workplace Carcinogens and the Risk of Development of Acute Leukemia in Infants. Case-Control Study.

    Science.gov (United States)

    Pérez-Saldivar, María Luisa; Fajardo-Gutiérrez, Arturo; Sierra-Ramírez, José Alfredo; Núñez-Villegas, Nancy; Pérez-Lorenzana, Héctor; Dorantes-Acosta, Elisa María; Román-Zepeda, Pedro Francisco; Rodríguez-Zepeda, María Del Carmen; González-Ulivarri, Juana Esther; López-Santiago, Norma; Martínez-Silva, Sofía Irene; Paredes-Aguilera, Rogelio; Velázquez-Aviña, Martha Margarita; Flores-Lujano, Janet; Jiménez-Hernández, Elva; Núñez-Enríquez, Juan Carlos; Bekker-Méndez, Vilma Carolina; Mejía-Aranguré, Juan Manuel

    2016-11-01

    Occupational exposure of parents to carcinogens is of great interest in the etiology of leukemias. Evidence of the impact of such exposure on infants or small children is scarce. Here we estimated whether occupational exposure of parents to carcinogens could be a risk factor for leukemias in their children. Cases of acute leukemia (AL) in infants ≤24 months old diagnosed in Mexico City (1998-2013) were included in a population-based, case-control study. Each of the 195 cases was matched with at least one healthy child (n = 369). For each of four exposure windows studied, the degree of exposure to carcinogens was determined for both parents by using a validated occupational exposure index. An unconditional logistic regression was carried out. Odds ratios (OR) and the 95% confidence intervals (CI) of the overall occupational exposure for parents during the four exposure windows indicated no association with risk of AL in their children. Pre-conception, the OR by the father 0.77 (0.49-1.21), by the mother 1.03 (0.50-2.11); during pregnancy, father 0.66 (0.38-1.15), mother 1.79 (0.46-6.90); during breastfeeding, father 0.75 (0.43-1.30), mother 0.96 (0.21-4.30); and after birth, father 0.74 (0.45-1.22), mother 0.90 (0.24-3.32). The statistical power of the sample size to identify an OR ≥2 and an exposure of ≥10% among controls was 78%. These data support the idea that parents' occupational exposure during any of the periods studied was not a risk factor contributing to the etiology of AL in infants ≤24 months of age. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  13. Improved outcome for children with acute lymphoblastic leukemia after risk-adjusted intensive therapy: a single institution experience

    International Nuclear Information System (INIS)

    Al-Nasser, A.; El-Solh, H.; Al-Mahr, M.

    2008-01-01

    Because of need for more comprehensive information on the least toxic and most effective forms of therapy for children with acute lymphoblastic leukemia (ALL), we reviewed our experience in the treatment of children with ALL at King Faisal Specialist Hospital and Research Centre (KFSHRC) and King Fahd National Center for Children's Cancer and Research (KFNCCCR) over a period of 18 years with a focus on patient characteristics and outcome. During the period of 1981 to 1988, records of children with ALL were retrospectively reviewed with respect to clinical presentation, laboratory findings, risk factors, stratification, therapy and outcome. The protocols used in treatment included 4 local protocols (KFSH 81, 84, 87 and 90) and subsequently. Children's Cancer Group (CCG) protocols and these were grouped as Era (1981-1992) and Era 2 (1993-1998). Of 509 children with ALL treated during this period, 316 were treated using local protocols and 193 using CCG protocols. Drugs used in Era 1 included a 4-drug induction using etoposid (VP-16) instead of L-asparaginase. Consolidation was based on high dose methotexate (MTX) 1g/m2 and maintenance was based on oral mercaptopurine (6-MP) and MTX with periodic pulses using intravenous teniposide (VM-26), Ara-C, L-asparaginase, adriamycin, prednisone, VP-16 cyclophosphamide .International protocols were introduced in Era 2, which was also marked by intensification of early treatment, a wider selection of cytoreductive agents, and the alternating use of non-cross-resistant pairs of drugs using the post-remission period. The end of induction remission rate improved from 90% in Era 1 to 95% in Era 2, which was of borderline statistical significance (P=0.49). The 5-year event-free survival (EFS) improved from 30.6% in Era 1 to 64.2% in Era 2 (P<.001). Improvement in outcome was achieved without any significant increase in morbidity or mortality, due to improvement in both systemic therapy and supportive care. The most important

  14. Secondary acute leukemia - review of 15 cases

    Energy Technology Data Exchange (ETDEWEB)

    Venugopal, P; Rajni, A; Gopal, R; Saikia, T; Kurkure, P A; Nair, C N; Advani, S H

    1988-12-01

    Acute leukemia is a rare complication of long-term chemotherapy, immunosuppressive therapy and radiotherapy. With improved survival in cancer patients resulting from modern methods of investigations and treatment, more case of secondary leukemia have come to light. In this review, fifteen cases of secondary leukemia, its prognostic implications and methods to reduce the risk of its development are emphasised. Relevant literature is also reviewed. (author). 3 tabs., 24 refs.

  15. Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following myelodysplastic syndrome

    DEFF Research Database (Denmark)

    Grövdal, Michael; Khan, Rasheed; Aggerholm, Anni

    2007-01-01

    was designed to assess the effect of methylation status on the outcome of conventional induction chemotherapy. EXPERIMENTAL DESIGN: Sixty patients with high-risk MDS or acute myeloid leukemia following MDS were treated with standard doses of daunorubicin and 1-beta-d-arabinofuranosylcytosine. Standard.......008), and CDH methylation retained its prognostic value also in the multivariate analysis. Hypermethylation was associated with increased CD34 expression, but not with other known predictive factors for response, such as cytogenetic profile. CONCLUSIONS: We show for the first time a significant effect...

  16. Residential exposures to indoor air pollutants could yield childhood leukemia risk levels similar to those associated with 60 Hz magnetic fields

    International Nuclear Information System (INIS)

    Easterly, C.E.

    1992-01-01

    Over a decade ago Easterly suggested that electromagnetic fields may be able to participate in a cooperative process leading to the expression of cancer. Evidence derived from the literature is presented to support the suggestion that potentially cooperative factors other than electromagnetic fields are present in homes in sufficient quantities to result in approximately the same risk levels as are being measured in epidemiology studies of childhood leukemia and electromagnetic fields. Generally these odds ratios vary from 1.5 to 2.5

  17. Motor skill delays in pre-school children with leukemia one year after treatment: Hematopoietic stem cell transplantation therapy as an important risk factor.

    Science.gov (United States)

    Taverna, Livia; Tremolada, Marta; Bonichini, Sabrina; Tosetto, Barbara; Basso, Giuseppe; Messina, Chiara; Pillon, Marta

    2017-01-01

    CNS-directed therapies for the treatment of leukemia can adversely affect the acquisition of new skills, such as reading/writing and math. Two years after the end of treatments, children show gross and fine motor skill delays that may persist even when patients are considered healed. The goal of the present study was to assess motor skills difficulties in pre-school children with leukemia one year after treatment. Particular attention has been paid to those patients who had undergone Hematopoietic Stem Cell Transplantation (HSCT) and to the relationship between motor delays and age bands. Participants were 60 children (median age of 5; inter quartile range: 3.07-5.76), including 31 females and 29 males, 91.7% of them were affected by acute lymphoblastic leukemia (ALL), and 8.3% by acute myeloid leukemia (AML). Five children had undergone HCST. Parents were interviewed by Vineland Adaptive Behavior Scales (VABS) on children's motor skills and filled in the Italian Temperament Questionnaire (QUIT). VABS's total scores were converted into equivalent mental age scores (EMA). A score difference of at least three months between current age and equivalent mental age was considered a developmental delay. Non-parametric analyses were run to understand if HSCT treatment and a specific age band influence children's motor skills. Significant delays were found in global motor skills (56.7%) as well as in fine and gross motor domains. Mann Whitney U tests showed that children with HSCT were reported to have lower gross motor mean ranks (U = 62; p = 0.004; Mean rank = 15.40) than peers without HSCT (Mean rank = 31.87) and lower mean rank values on motor temperament scale (U = 9; p = 0.003; HSCT Mean rank = 4.75 versus no HSCT Mean rank = 27.81). Kruskal Wallis' tests identified the high risk treatment showing that HSCT experience negatively impacted the motor skills and temperamental motor activity of pre-school children one year after the diagnosis of leukemia.

  18. Motor skill delays in pre-school children with leukemia one year after treatment: Hematopoietic stem cell transplantation therapy as an important risk factor.

    Directory of Open Access Journals (Sweden)

    Livia Taverna

    Full Text Available CNS-directed therapies for the treatment of leukemia can adversely affect the acquisition of new skills, such as reading/writing and math. Two years after the end of treatments, children show gross and fine motor skill delays that may persist even when patients are considered healed. The goal of the present study was to assess motor skills difficulties in pre-school children with leukemia one year after treatment. Particular attention has been paid to those patients who had undergone Hematopoietic Stem Cell Transplantation (HSCT and to the relationship between motor delays and age bands. Participants were 60 children (median age of 5; inter quartile range: 3.07-5.76, including 31 females and 29 males, 91.7% of them were affected by acute lymphoblastic leukemia (ALL, and 8.3% by acute myeloid leukemia (AML. Five children had undergone HCST. Parents were interviewed by Vineland Adaptive Behavior Scales (VABS on children's motor skills and filled in the Italian Temperament Questionnaire (QUIT. VABS's total scores were converted into equivalent mental age scores (EMA. A score difference of at least three months between current age and equivalent mental age was considered a developmental delay. Non-parametric analyses were run to understand if HSCT treatment and a specific age band influence children's motor skills. Significant delays were found in global motor skills (56.7% as well as in fine and gross motor domains. Mann Whitney U tests showed that children with HSCT were reported to have lower gross motor mean ranks (U = 62; p = 0.004; Mean rank = 15.40 than peers without HSCT (Mean rank = 31.87 and lower mean rank values on motor temperament scale (U = 9; p = 0.003; HSCT Mean rank = 4.75 versus no HSCT Mean rank = 27.81. Kruskal Wallis' tests identified the high risk treatment showing that HSCT experience negatively impacted the motor skills and temperamental motor activity of pre-school children one year after the diagnosis of leukemia.

  19. Motor skill delays in pre-school children with leukemia one year after treatment: Hematopoietic stem cell transplantation therapy as an important risk factor

    Science.gov (United States)

    Bonichini, Sabrina; Tosetto, Barbara; Basso, Giuseppe; Messina, Chiara; Pillon, Marta

    2017-01-01

    CNS-directed therapies for the treatment of leukemia can adversely affect the acquisition of new skills, such as reading/writing and math. Two years after the end of treatments, children show gross and fine motor skill delays that may persist even when patients are considered healed. The goal of the present study was to assess motor skills difficulties in pre-school children with leukemia one year after treatment. Particular attention has been paid to those patients who had undergone Hematopoietic Stem Cell Transplantation (HSCT) and to the relationship between motor delays and age bands. Participants were 60 children (median age of 5; inter quartile range: 3.07–5.76), including 31 females and 29 males, 91.7% of them were affected by acute lymphoblastic leukemia (ALL), and 8.3% by acute myeloid leukemia (AML). Five children had undergone HCST. Parents were interviewed by Vineland Adaptive Behavior Scales (VABS) on children’s motor skills and filled in the Italian Temperament Questionnaire (QUIT). VABS’s total scores were converted into equivalent mental age scores (EMA). A score difference of at least three months between current age and equivalent mental age was considered a developmental delay. Non-parametric analyses were run to understand if HSCT treatment and a specific age band influence children’s motor skills. Significant delays were found in global motor skills (56.7%) as well as in fine and gross motor domains. Mann Whitney U tests showed that children with HSCT were reported to have lower gross motor mean ranks (U = 62; p = 0.004; Mean rank = 15.40) than peers without HSCT (Mean rank = 31.87) and lower mean rank values on motor temperament scale (U = 9; p = 0.003; HSCT Mean rank = 4.75 versus no HSCT Mean rank = 27.81). Kruskal Wallis’ tests identified the high risk treatment showing that HSCT experience negatively impacted the motor skills and temperamental motor activity of pre-school children one year after the diagnosis of leukemia. PMID

  20. The impact of CYP3A5*3 on risk and prognosis in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Borst, Louise; Wallerek, Sandra; Dalhoff, Kim

    2011-01-01

    Objectives: Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood; however, little is known of the molecular etiology and environmental exposures causing the disease. Cytochrome P450 3A5 (CYP3A5) plays a crucial role in the catalytic oxidation of endogenous metabolites and toxic...

  1. The impact of CYP3A5*3 on risk and prognosis in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Borst, Louise; Wallerek, Sandra; Dalhoff, Kim Peder

    2011-01-01

    Objectives:  Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood; however, little is known of the molecular etiology and environmental exposures causing the disease. Cytochrome P450 3A5 (CYP3A5) plays a crucial role in the catalytic oxidation of endogenous metabolites...

  2. High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation

    NARCIS (Netherlands)

    Marshall, G. M.; Dalla Pozza, L.; Sutton, R.; Ng, A.; de Groot-Kruseman, Ha; van der Velden, V. H.; Venn, N. C.; van den Berg, H.; de Bont, E. S. J. M.; Egeler, R. Maarten; Hoogerbrugge, P. M.; Kaspers, G. J. L.; Bierings, M. B.; van der Schoot, E.; van Dongen, J.; Law, T.; Cross, S.; Mueller, H.; de Haas, V.; Haber, M.; Revesz, T.; Alvaro, F.; Suppiah, R.; Norris, M. D.; Pieters, R.

    Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9; 22)-negative ALL, were

  3. High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation.

    NARCIS (Netherlands)

    Marshall, G.M.; Pozza, L. Dalla; Sutton, R.; Ng, A.; Groot-Kruseman, H.A. de; Velden, V.H. van der; Venn, N.C.; Berg, H. van den; Bont, E.S. de; rten Egeler, R. Maa; Hoogerbrugge, P.M.; Kaspers, G.J.L.; Bierings, M.B.; Schoot, E. van der; Dongen, J. Van; Law, T.; Cross, S.; Mueller, H.; Haas, V. de; Haber, M.; Revesz, T.; Alvaro, F.; Suppiah, R.; Norris, M.D.; Pieters, R.

    2013-01-01

    Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9;22)-negative ALL, were

  4. High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation

    NARCIS (Netherlands)

    Marshall, G. M.; Dalla Pozza, L.; Sutton, R.; Ng, A.; de Groot-Kruseman, H. A.; van der Velden, V. H.; Venn, N. C.; van den Berg, H.; de Bont, E. S. J. M.; Egeler, R. Maarten; Hoogerbrugge, P. M.; Kaspers, G. J. L.; Bierings, M. B.; van der Schoot, E.; van Dongen, J.; Law, T.; Cross, S.; Mueller, H.; de Haas, V.; Haber, M.; Révész, T.; Alvaro, F.; Suppiah, R.; Norris, M. D.; Pieters, R.

    2013-01-01

    Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9;22)-negative ALL, were

  5. Combined Haploidentical and Umbilical Cord Blood Allogeneic Stem Cell Transplantation for High-Risk Lymphoma and Chronic Lymphoblastic Leukemia.

    Science.gov (United States)

    Hsu, Jingmei; Artz, Andrew; Mayer, Sebastian A; Guarner, Danielle; Bishop, Michael R; Reich-Slotky, Ronit; Smith, Sonali M; Greenberg, June; Kline, Justin; Ferrante, Rosanna; Phillips, Adrienne A; Gergis, Usama; Liu, Hongtao; Stock, Wendy; Cushing, Melissa; Shore, Tsiporah B; van Besien, Koen

    2018-02-01

    Limited studies have reported on outcomes for lymphoid malignancy patients receiving alternative donor allogeneic stem cell transplants. We have previously described combining CD34-selected haploidentical grafts with umbilical cord blood (haplo-cord) to accelerate neutrophil and platelet engraftment. Here, we examine the outcome of patients with lymphoid malignancies undergoing haplo-cord transplantation at the University of Chicago and Weill Cornell Medical College. We analyzed 42 lymphoma and chronic lymphoblastic leukemia (CLL) patients who underwent haplo-cord allogeneic stem cell transplantation. Patients underwent transplant for Hodgkin lymphoma (n = 9, 21%), CLL (n = 5, 12%) and non-Hodgkin lymphomas (n = 28, 67%), including 13 T cell lymphomas. Twenty-four patients (52%) had 3 or more lines of therapies. Six (14%) and 1 (2%) patients had prior autologous and allogeneic stem cell transplant, respectively. At the time of transplant 12 patients (29%) were in complete remission, 18 had chemotherapy-sensitive disease, and 12 patients had chemotherapy-resistant disease. Seven (17%), 11 (26%), and 24 (57%) patients had low, intermediate, and high disease risk index before transplant. Comorbidity index was evenly distributed among 3 groups, with 13 (31%), 14 (33%), and 15 (36%) patients scoring 0, 1 to 2, and ≥3. Median age for the cohort was 49 years (range, 23 to 71). All patients received fludarabine/melphalan/antithymocyte globulin conditioning regimen and post-transplant graft-versus-host disease (GVHD) prophylaxis with tacrolimus and mycophenolate mofetil. The median time to neutrophil engraftment was 11 days (range, 9 to 60) and to platelet engraftment 19.5 days (range, 11 to 88). Cumulative incidence of nonrelapse mortality was 11.6% at 100 days and 19 % at one year. Cumulative incidence of relapse was 9.3% at 100 days and 19% at one year. With a median follow-up of survivors of 42 months, the 3-year rates of GVHD relapse free survival

  6. Perceived risk and trust associated with purchasing at electronic marketplaces

    NARCIS (Netherlands)

    Verhagen, T.; Meents, S.; Tan, Y.H.

    2006-01-01

    Understanding consumer behaviour is of vital importance to consumer-oriented e-business models today. In this paper, we study the relationships between consumer perceptions of risk and trust and the attitude towards purchasing at a consumer-to-consumer electronic marketplace (EM). Typical for EM

  7. Leukemia and lymphoma in atomic bomb survivors

    International Nuclear Information System (INIS)

    Finch, S.C.

    1984-01-01

    Leukemia has been observed to increase with increasing radiation dose in the A-bomb survivors of Hiroshima and Nagasaki. The first radiation-related cases occurred 3 to 5 years following exposure. The peak incidence years were about 7 to 8 years following exposure and the leukemogenic effect has decreased since that time, but it may last for 40 years or longer in the most heavily exposed persons. A bimodal susceptibility pattern was observed, with peaks following exposure during childhood and after age 50. Latent periods for the development of acute leukemia were shortest in the younger exposed persons. Both acute and chronic forms of leukemia occurred in exposed persons at younger ages in life than normally is expected. The most common types of radiation-induced leukemia were acute and chronic granulocytic in adults and children, and acute lymphocytic in children. The highest radiation-related leukemia risk was for chronic granulocytic leukemia following childhood exposure

  8. SNP association mapping across the extended major histocompatibility complex and risk of B-cell precursor acute lymphoblastic leukemia in children.

    Directory of Open Access Journals (Sweden)

    Kevin Y Urayama

    Full Text Available The extended major histocompatibility complex (xMHC is the most gene-dense region of the genome and harbors a disproportionately large number of genes involved in immune function. The postulated role of infection in the causation of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL suggests that the xMHC may make an important contribution to the risk of this disease. We conducted association mapping across an approximately 4 megabase region of the xMHC using a validated panel of single nucleotide polymorphisms (SNPs in childhood BCP-ALL cases (n=567 enrolled in the Northern California Childhood Leukemia Study (NCCLS compared with population controls (n=892. Logistic regression analyses of 1,145 SNPs, adjusted for age, sex, and Hispanic ethnicity indicated potential associations between several SNPs and childhood BCP-ALL. After accounting for multiple comparisons, one of these included a statistically significant increased risk associated with rs9296068 (OR=1.40, 95% CI=1.19-1.66, corrected p=0.036, located in proximity to HLA-DOA. Sliding window haplotype analysis identified an additional locus located in the extended class I region in proximity to TRIM27 tagged by a haplotype comprising rs1237485, rs3118361, and rs2032502 (corrected global p=0.046. Our findings suggest that susceptibility to childhood BCP-ALL is influenced by genetic variation within the xMHC and indicate at least two important regions for future evaluation.

  9. Chronic Myelogenous Leukemia

    Science.gov (United States)

    Chronic myelogenous leukemia Overview Chronic myelogenous leukemia (CML) is an uncommon type of cancer of the blood cells. The term "chronic" in chronic myelogenous leukemia indicates that this cancer ...

  10. Ionizing radiation and risk of chronic lymphocytic leukemia in the 15-country study of nuclear industry workers

    DEFF Research Database (Denmark)

    Vrijheid, Martine; Cardis, Elisabeth; Ashmore, Patrick

    2008-01-01

    In contrast to other types of leukemia, chronic lymphocytic leukemia (CLL) has long been regarded as non-radiogenic, i.e. not caused by ionizing radiation. However, the justification for this view has been challenged. We therefore report on the relationship between CLL mortality and external...... ionizing radiation dose within the 15-country nuclear workers cohort study. The analyses included, in seven countries with CLL deaths, a total of 295,963 workers with more than 4.5 million person-years of follow-up and an average cumulative bone marrow dose of 15 mSv; there were 65 CLL deaths....... In conclusion, the largest nuclear workers cohort study to date finds little evidence for an association between low doses of external ionizing radiation and CLL mortality. This study had little power due to low doses, short follow-up periods, and uncertainties in CLL ascertainment from death certificates...

  11. Allogeneic bone marrow transplantation with conditioning regimen of total body irradiation/busulfan/melphalan for 16 patients in children with high-risk leukemia and lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Yoshihara, Takao; Fujii, Noriko [Matsushita Memorial Hospital, Moriguchi, Osaka (Japan); Naya, Mayumi [and others

    1999-02-01

    We report the therapeutic results of allogeneic bone marrow transplantations (BMT) for 16 children with high-risk leukemia and lymphoma. The conditioning regimen consisted of total body irradiation (TBI) (12 Gy), busulfan (Bu) (4 mg/kg x 2 days), and melphalan (L-PAM) (70 mg/m{sup 2} x 2 or 3 days). Graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporin (CsA) + methotrexate (MTX) (4 cases) and CsA + MTX-methyl-prednisolone (11 cases). Seven patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 B-cell type non-Hodgkin`s lymphoma, and 1 peripheral T-cell lymphoma. Nine patients were in complete remission (CR) and 7 in non CR at BMT. Nine patients received transplants from HLA-matched related (MR) donors, 4 from HLA-mismatched related (MisR) donors, and 3 from unrelated (UR) donors. Seven of the cases, all of which were transplanted from MR, have continued complete remission for 15-47 (median 27) months. Nine patients, of which seven were transplanted from MisR/UR, died from complications from fungal pneumonia (3), cytomegalovirus pneumonitis (1), GVHD (1), rhabdomyolysis (1), lymphoproliferative disorder (1), rejection (1), and relapse (1). These results suggest that the combination of TBI, Bu, and L-PAM as a BMT regimen has a significant anti-neoplastic benefit and is considered to be useful; however, considering the high rate of fatal transplant-related complications, more refinement is required, especially for transplants from MisR and UR donors. (author)

  12. Allogeneic bone marrow transplantation with conditioning regimen of total body irradiation/busulfan/melphalan for 16 patients in children with high-risk leukemia and lymphoma

    International Nuclear Information System (INIS)

    Yoshihara, Takao; Fujii, Noriko; Naya, Mayumi

    1999-01-01

    We report the therapeutic results of allogeneic bone marrow transplantations (BMT) for 16 children with high-risk leukemia and lymphoma. The conditioning regimen consisted of total body irradiation (TBI) (12 Gy), busulfan (Bu) (4 mg/kg x 2 days), and melphalan (L-PAM) (70 mg/m 2 x 2 or 3 days). Graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporin (CsA) + methotrexate (MTX) (4 cases) and CsA + MTX-methyl-prednisolone (11 cases). Seven patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 B-cell type non-Hodgkin's lymphoma, and 1 peripheral T-cell lymphoma. Nine patients were in complete remission (CR) and 7 in non CR at BMT. Nine patients received transplants from HLA-matched related (MR) donors, 4 from HLA-mismatched related (MisR) donors, and 3 from unrelated (UR) donors. Seven of the cases, all of which were transplanted from MR, have continued complete remission for 15-47 (median 27) months. Nine patients, of which seven were transplanted from MisR/UR, died from complications from fungal pneumonia (3), cytomegalovirus pneumonitis (1), GVHD (1), rhabdomyolysis (1), lymphoproliferative disorder (1), rejection (1), and relapse (1). These results suggest that the combination of TBI, Bu, and L-PAM as a BMT regimen has a significant anti-neoplastic benefit and is considered to be useful; however, considering the high rate of fatal transplant-related complications, more refinement is required, especially for transplants from MisR and UR donors. (author)

  13. Residential mobility and childhood leukemia.

    Science.gov (United States)

    Amoon, A T; Oksuzyan, S; Crespi, C M; Arah, O A; Cockburn, M; Vergara, X; Kheifets, L

    2018-07-01

    Studies of environmental exposures and childhood leukemia studies do not usually account for residential mobility. Yet, in addition to being a potential risk factor, mobility can induce selection bias, confounding, or measurement error in such studies. Using data collected for California Powerline Study (CAPS), we attempt to disentangle the effect of mobility. We analyzed data from a population-based case-control study of childhood leukemia using cases who were born in California and diagnosed between 1988 and 2008 and birth certificate controls. We used stratified logistic regression, case-only analysis, and propensity-score adjustments to assess predictors of residential mobility between birth and diagnosis, and account for potential confounding due to residential mobility. Children who moved tended to be older, lived in housing other than single-family homes, had younger mothers and fewer siblings, and were of lower socioeconomic status. Odds ratios for leukemia among non-movers living mobility, including dwelling type, increased odds ratios for leukemia to 2.61 (95% CI: 1.76-3.86) for living mobility of childhood leukemia cases varied by several sociodemographic characteristics, but not by the distance to the nearest power line or calculated magnetic fields. Mobility appears to be an unlikely explanation for the associations observed between power lines exposure and childhood leukemia. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Acute childhood leukemia: Nursing care

    International Nuclear Information System (INIS)

    Zietz, Hallie A

    1997-01-01

    Modern therapy for childhood acute leukemia has provided a dramatically improved prognosis over that of just 30 years ago. In the early 1960's survival rates for acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML) were 4% and 3%, respectively. By the 1980's survival rates had risen to 72% for all and 25% to 40% for AML. Today, a diagnosis of all carries an 80% survival rate and as high as a 90% survival rate for some low-risk subtypes. Such high cure rates depend on intense and complex, multimodal therapeutic protocols. Therefore, nursing care of the child with acute leukemia must meet the demands of complicated medical therapies and balance those with the needs of a sick child and their concerned family. An understanding of disease process and principles of medical management guide appropriate and effective nursing interventions. Leukemia is a malignant disorder of the blood and blood- forming organs (bone marrow, lymph nodes and spleen). Most believe that acute leukemia results from a malignant transformation of a single early haematopoietic stem cell that is capable of indefinite self-renewal. These immature cells of blasts do not respond to normal physiologic stimuli for differentiation and gradually become the predominant cell in the bone marrow

  15. Ibrutinib as a bridge to transplant in high-risk chronic lymphocytic leukemia: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Arcari Annalisa

    2017-01-01

    Full Text Available The treatment landscape of chronic lymphocytic leukemia (CLL has been challenged by the advent of novel classes of drugs, such as B-cell receptor (BCR-inhibitors and BCL-2 antagonists. In selected high-risk patients, the choice to start allogeneic hematopoietic stem cell transplantation (alloHCT or continue these agents is a matter of debate. Furthermore, published data about the impact on the feasibility of alloHCT and the optimal timing of administration are limited. Here we present a case of relapsed TP53 mutated CLL treated with ibrutinib as a bridge to alloHCT, discussing risks and benefits of different treatment options in a “real life” situation.

  16. An intron splice acceptor polymorphism in hMSH2 and risk of leukemia after treatment with chemotherapeutic alkylating agents.

    Science.gov (United States)

    Worrillow, Lisa J; Travis, Lois B; Smith, Alexandra G; Rollinson, Sara; Smith, Andrew J; Wild, Christopher P; Holowaty, Eric J; Kohler, Betsy A; Wiklund, Tom; Pukkala, Eero; Roman, Eve; Morgan, Gareth J; Allan, James M

    2003-08-01

    We sought to determine whether the -6 exon 13 T>C polymorphism in the DNA mismatch repair gene hMSH2 modulates susceptibility to acute myeloid leukemia after therapy and particularly after O(6)-guanine alkylating chemotherapy. We also determined the extent of microsatellite instability (MSI) in therapy-related acute myeloid leukemia (t-AML) as a marker of dysfunctional DNA mismatch repair. Using a novel restriction fragment length polymorphism, verified by direct sequencing, we have genotyped 91 t-AML cases, 420 de novo acute myeloid leukemia cases, and 837 controls for the hMSH2 -6 exon 13 polymorphism. MSI was evaluated in presentation bone marrow from 34 cases using the mononucleotide microsatellite markers BAT16, BAT25, and BAT26. Distribution of the hMSH2 -6 exon 13 polymorphism was not significantly different between de novo acute myeloid leukemia cases and controls, with heterozygotes and homozygotes for the variant (C) allele representing 12.2 and 1.6%, respectively, of the control population. However, the variant (C) hMSH2 allele was significantly overrepresented in t-AML cases that had previously been treated with O(6)-guanine alkylating agents, including cyclophosphamide and procarbazine, compared with controls (odds ratio, 4.02; 95% confidence interval, 1.40-11.37). Thirteen of 34 (38%) t-AML cases were MSI positive, and 2 of these 13 cases were homozygous for the variant (C) allele, a frequency substantially higher than in the control population. Association of the hMSH2 -6 exon 13 variant (C) allele with leukemia after O(6)-guanine alkylating agents implicates this allele in conferring a nondisabling DNA mismatch repair defect with concomitant moderate alkylation tolerance, which predisposes to the development of t-AML via the induction of DNA mismatch repair-disabling mutations and high-grade MSI. Homozygosity for the hMSH2 variant in 2 of 13 MSI-positive t-AML cases provides some support for this model.

  17. A cytogenetic model predicts relapse risk and survival in patients with acute myeloid leukemia undergoing hematopoietic stem cell transplantation in morphologic complete remission.

    Science.gov (United States)

    Rashidi, Armin; Cashen, Amanda F

    2015-01-01

    Up to 30% of patients with acute myeloid leukemia (AML) and abnormal cytogenetics have persistent cytogenetic abnormalities (pCytAbnl) at morphologic complete remission (mCR). We hypothesized that the prognostic significance of pCytAbnl in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) in mCR varies with cytogenetic risk group. We analyzed the data on 118 patients with AML and abnormal cytogenetics who underwent HSCT in mCR, and developed a risk stratification model based on pCytAbnl and cytogenetic risk group. The model distinguished three groups of patients (Pcytogenetics (n=25) had the shortest median time to relapse (TTR; 5 months), relapse-free survival (RFS; 3 months), and overall survival (OS; 7 months). The group with favorable/intermediate risk cytogenetics and without pCytAbnl (n=43) had the longest median TTR (not reached), RFS (57 months), and OS (57 months). The group with pCytAbnl and favorable/intermediate risk cytogenetics, or, without pCytAbnl but with unfavorable risk cytogenetics (n=50) experienced intermediate TTR (18 months), RFS (9 months), and OS (18 months). In conclusion, a cytogenetic risk model identifies patients with AML in mCR with distinct rates of relapse and survival following HSCT. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Very Low Dose Fetal Exposure to Chernobyl Contamination Resulted in Increases in Infant Leukemia in Europe and Raises Questions about Current Radiation Risk Models

    Directory of Open Access Journals (Sweden)

    Christopher C. Busby

    2009-12-01

    Full Text Available Following contamination from the Chernobyl accident in April 1986 excess infant leukemia (0–1 y was reported from five different countries, Scotland, Greece, Germany, Belarus and Wales and Scotland combined. The cumulative absorbed doses to the fetus, as conventionally assessed, varied from 0.02 mSv in the UK through 0.06 mSv in Germany, 0.2 mSv in Greece and 2 mSv in Belarus, where it was highest. Nevertheless, the effect was real and given the specificity of the cohort raised questions about the safety of applying the current radiation risk model of the International Commission on Radiological Protection (ICRP to these internal exposures, a matter which was discussed in 2000 by Busby and Cato [7,8] and also in the reports of the UK Committee examining Radiation Risk from Internal Emitters. Data on infant leukemia in the United Kingdom, chosen on the basis of the cohorts defined by the study of Greece were supplied by the UK Childhood Cancer Research Group. This has enabled a study of leukemia in the combined infant population of 15,466,845 born in the UK, Greece, and Germany between 1980 and 1990. Results show a statistically significant excess risk RR = 1.43 (95% CI 1.13 < RR < 1.80 (2-tailed; p = 0.0025 in those born during the defined peak exposure period of 01/07/86 to 31/12/87 compared with those born between 01/01/80 and 31/12/85 and 01/01/88 and 31/12/90. The excess risks in individual countries do not increase monotonically with the conventionally calculated doses, the relation being biphasic, increasing sharply at low doses and falling at high doses. This result is discussed in relation to fetal/cell death at higher doses and also to induction of DNA repair. Since the cohort is chosen specifically on the basis of exposure to internal radionuclides, the result can be expressed as evidence for a significant error in the conventional modeling for such internal fetal exposures.

  19. THE ROLE OF TRUST AND PERCEIVED RISK IN ELECTRONIC COMMERCE

    Directory of Open Access Journals (Sweden)

    NICULA DANA LAURA

    2014-05-01

    Full Text Available Trust and risk are very important in consumers' electronic commerce purchasing decisions. How do trust and risk affect an Internet consumer's purchasing decision? To answer this question I’ve developed a theoretical framework describing the trust-based decision-making process a consumer uses when making a purchase from a given site. Consumer disposition to trust, reputation, privacy concerns, security concerns, the information quality of the Website, and the company's reputation, have strong effects on Internet consumers' trust in the Website.

  20. Electronic cigarettes: incorporating human factors engineering into risk assessments

    OpenAIRE

    Yang, Ling; Rudy, Susan F; Cheng, James M; Durmowicz, Elizabeth L

    2014-01-01

    Objective A systematic review was conducted to evaluate the impact of human factors (HF) on the risks associated with electronic cigarettes (e-cigarettes) and to identify research gaps. HF is the evaluation of human interactions with products and includes the analysis of user, environment and product complexity. Consideration of HF may mitigate known and potential hazards from the use and misuse of a consumer product, including e-cigarettes. Methods Five databases were searched through Januar...

  1. Profile of imatinib in pediatric leukemia

    Directory of Open Access Journals (Sweden)

    Burke MJ

    2014-02-01

    Full Text Available Michael J BurkeDepartment of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplantation, Medical College of Wisconsin, Milwaukee, WI, USAAbstract: Using targeted therapy for treatment of cancer has become the paradigm to which clinical trials aspire. Imatinib, the BCR-ABL1 tyrosine kinase inhibitor (TKI, was the first of its kind to specifically target and inhibit the underlying Philadelphia chromosome (Ph+ oncogene found to be driving chronic myeloid leukemia in adults, and has since become standard of care for the treatment of chronic myeloid leukemia in children. Imatinib, with its ability to target Ph+ leukemia, has been successfully incorporated into the treatment of not only pediatric chronic myeloid leukemia but also Ph+ acute lymphoblastic leukemia. With the incorporation of imatinib into combination chemotherapy for pediatric Ph+ acute lymphoblastic leukemia, current survival rates are far higher than at any other time for this once dreadful disease. With more children today receiving treatment with imatinib for either chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia, knowledge is accumulating surrounding the short-term and long-term toxicities observed in children, adolescents, and young adults treated with this TKI. In summary, the TKI imatinib has made a historic impact in the treatment of pediatric Ph+ leukemias, transforming what were once very high-risk diseases with considerable morbidity and mortality into ones that are now very treatable but with a new awareness surrounding the long-term toxicities that may come with this price for cure.Keywords: imatinib, leukemia, lymphoblastic leukemia, chronic myeloid leukemia, pediatric

  2. Medical history, lifestyle, family history, and occupational risk factors for adult acute lymphocytic leukemia: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.

    Science.gov (United States)

    Skibola, Christine F; Slager, Susan L; Berndt, Sonja I; Lightfoot, Tracy; Sampson, Joshua N; Morton, Lindsay M; Weisenburger, Dennis D

    2014-08-01

    Acute lymphoblastic leukemia/lymphoma (ALL) in adults is a rare malignancy with a poor clinical outcome, and few reported etiologic risk factors. We performed an exploratory pooled study of 152 ALL cases and 23096 controls from 16 case-control studies to investigate the role of medical history, lifestyle, family history, and occupational risk factors and risk of ALL. Age- race/ethnicity-, sex-, and study-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. An increased risk of ALL was found in those with a family history of a hematological malignancy (OR = 2.6, 95% CI = 1.22 to 5.54) and in leather (OR = 3.91, 95% CI = 1.35 to 11.35) and sewing/embroidery workers (OR = 2.92, 95% CI = 1.00 to 8.49). Consumers of alcohol had an increased risk of B-cell ALL (OR = 2.87, 95% CI = 1.18 to 6.95). The small number of statistically significant risk factors identified out of the 112 variables examined could be chance findings and will require further replication to assess their role in the etiology of adult ALL. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Vehicle rollover risk and electronic stability control systems.

    Science.gov (United States)

    MacLennan, P A; Marshall, T; Griffin, R; Purcell, M; McGwin, G; Rue, L W

    2008-06-01

    Electronic stability control (ESC) systems were developed to reduce motor vehicle collisions (MVCs) caused by loss of control. Introduced in Europe in 1995 and in the USA in 1996, ESC is designed to improve vehicle lateral stability by electronically detecting and automatically assisting drivers in unfavorable situations. To examine the relationship between vehicle rollover risk and presence of ESC using a large national database of MVCs. A retrospective cohort study for the period 1995 through 2006 was carried out using data obtained from the National Automotive Sampling System General Estimates System. All passenger cars and sport utility vehicles (SUVs)/vans of model year 1996 and later were eligible. Vehicle ESC (unavailable, optional, standard) was determined on the basis of make, model, and model year. Risk ratios (RRs) and 95% CIs were calculated to compare rollover risk by vehicle ESC group. For all crashes, vehicles equipped with standard ESC had decreased risk of rollover (RR = 0.62, 95% CI 0.50 to 0.77) compared with vehicles with ESC unavailable. The association was consistent for single-vehicle MVCs (RR = 0.61, 95% CI 0.46 to 0.82); passenger cars had decreased rollover risk (RR = 0.77, 95% CI 0.52 to 1.12), but SUVs/vans had a more dramatically decreased risk (RR = 0.40, 95% CI 0.26 to 0.61). This study supports previous results showing ESC to be effective in reducing the risk of rollover. ESC is more effective in SUVs/vans for rollovers related to single-vehicle MVCs.

  4. Development of a modified prognostic index for patients with aggressive adult T-cell leukemia-lymphoma aged 70 years or younger: possible risk-adapted management strategies including allogeneic transplantation.

    Science.gov (United States)

    Fuji, Shigeo; Yamaguchi, Takuhiro; Inoue, Yoshitaka; Utsunomiya, Atae; Moriuchi, Yukiyoshi; Uchimaru, Kaoru; Owatari, Satsuki; Miyagi, Takashi; Taguchi, Jun; Choi, Ilseung; Otsuka, Eiichi; Nakachi, Sawako; Yamamoto, Hisashi; Kurosawa, Saiko; Tobinai, Kensei; Fukuda, Takahiro

    2017-07-01

    Adult T-cell leukemia-lymphoma is a distinct type of peripheral T-cell lymphoma caused by human T-cell lymphotropic virus type I. Although allogeneic stem cell transplantation after chemotherapy is a recommended treatment option for patients with aggressive adult T-cell leukemia-lymphoma, there is no consensus about indications for allogeneic stem cell transplantation because there is no established risk stratification system for transplant eligible patients. We conducted a nationwide survey of patients with aggressive adult T-cell leukemia-lymphoma in order to construct a new, large database that includes 1,792 patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who were diagnosed between 2000 and 2013 and received intensive first-line chemotherapy. We randomly divided patients into two groups (training and validation sets). Acute type, poor performance status, high soluble interleukin-2 receptor levels (> 5,000 U/mL), high adjusted calcium levels (≥ 12 mg/dL), and high C-reactive protein levels (≥ 2.5 mg/dL) were independent adverse prognostic factors used in the training set. We used these five variables to divide patients into three risk groups. In the validation set, median overall survival for the low-, intermediate-, and high-risk groups was 626 days, 322 days, and 197 days, respectively. In the intermediate- and high-risk groups, transplanted recipients had significantly better overall survival than non-transplanted patients. We developed a promising new risk stratification system to identify patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who may benefit from upfront allogeneic stem cell transplantation. Prospective studies are warranted to confirm the benefit of this treatment strategy. Copyright© 2017 Ferrata Storti Foundation.

  5. Leukemia revisited

    Energy Technology Data Exchange (ETDEWEB)

    Cronkite, E P

    1980-01-01

    Selected features of the historical development of our knowledge of leukemia are discussed. The use of different methodologies for study of the nature of leukemic cell proliferation are analyzed. The differences between older cell kinetic data using tritiated thymidine and autoradiography and the newer cell culture methods are more apparent than real. It is suggested that tritiated thymidine and extracorporeal irradiation of the blood may be useful for therapeutic agents that have not been given an adequate trial. Radiation leukemogenesis presents an opportunity for study of the nature of leukemogenesis that has not been exploited adequately.

  6. Leukemia revisited

    International Nuclear Information System (INIS)

    Cronkite, E.P.

    1980-01-01

    Selected features of the historical development of our knowledge of leukemia are discussed. The use of different methodologies for study of the nature of leukemic cell proliferation are analyzed. The differences between older cell kinetic data using tritiated thymidine and autoradiography and the newer cell culture methods are more apparent than real. It is suggested that tritiated thymidine and extracorporeal irradiation of the blood may be useful for therapeutic agents that have not been given an adequate trial. Radiation leukemogenesis presents an opportunity for study of the nature of leukemogenesis that has not been exploited adequately

  7. Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Simonsson, Bengt; Gedde-Dahl, Tobias; Markevärn, Berit

    2011-01-01

    Biologic and clinical observations suggest that combining imatinib with IFN-a may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission......%) discontinued imatinib treatment (1 because of blastic transformation in imatinib arm). In addition, in the combination arm, 34 patients (61%) discontinued Peg-IFN-a2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg-IFN-a2b arm (82%) compared...... with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg-IFN-a2b treatment ( 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg-IFN-a2b to imatinib markedly increased the MMR rate at 12 months...

  8. High-Risk Microgranular Acute Promyelocytic Leukemia with a Five-Way Complex Translocation Involving PML-RARA

    Directory of Open Access Journals (Sweden)

    Benjamin Powers

    2015-01-01

    Full Text Available Acute promyelocytic leukemia (APL is classically characterized by chromosomal translocation (15;17, resulting in the PML-RARA fusion protein leading to disease. Here, we present a case of a 50-year-old man who presented with signs and symptoms of acute leukemia with concern for APL. Therapy was immediately initiated with all-trans retinoic acid. The morphology of his leukemic blasts was consistent with the hypogranular variant of APL. Subsequent FISH and cytogenetic analysis revealed a unique translocation involving five chromosomal regions: 9q34, 17q21, 15q24, 12q13, and 15q26.1. Molecular testing demonstrated PML/RARA fusion transcripts. Treatment with conventional chemotherapy was added and he went into a complete remission. Given his elevated white blood cell count at presentation, intrathecal chemotherapy for central nervous system prophylaxis was also given. The patient remains on maintenance therapy and remains in remission. This is the first such report of a 5-way chromosomal translocation leading to APL. Similar to APL with chromosomal translocations other than classical t(15;17 which result in the typical PML-RARA fusion, our patient responded promptly to an ATRA-containing regimen and remains in complete remission.

  9. The leukemias: Epidemiologic aspects

    International Nuclear Information System (INIS)

    Linet, M.S.

    1984-01-01

    Particularly geared to physicians and cancer researchers, this study of the epidemiology and etiology of leukemia analyzes the four major leukemia subtypes in terms of genetic and familial determinant factors and examines the incidence, distribution and frequency of reported leukemia clusters. Linet discusses the connection between other types of malignancies, their treatments, and the subsequent development of leukemia and evaluates the impact on leukemia onset of such environmental factors as radiation therapy, drugs, and occupational hazards

  10. Leukemia -- Chronic T-Cell Lymphocytic

    Science.gov (United States)

    ... social workers, and patient advocates. Cancer.Net Guide Leukemia - Chronic T-Cell Lymphocytic Introduction Statistics Risk Factors Symptoms and Signs Diagnosis Stages Treatment Options About Clinical Trials Latest Research ...

  11. General Information About Hairy Cell Leukemia

    Science.gov (United States)

    ... Other Myeloid Malignancies Treatment . Chronic Myelogenous Leukemia Treatment . Gender and age may affect the risk of hairy ... in the shape of blood cells. Blood chemistry studies : A procedure in which a blood sample is ...

  12. [Acute myeloid leukemia].

    Science.gov (United States)

    Tabuchi, Ken

    2007-02-01

    The annual incident rate of pediatric acute myeloid leukemia (AML) is now 10 per million in Japan, against 5 to 9 per million in the USA and Europe. Overall long-term survival has now been achieved for more than 50% of pediatric patients with AML in the USA and in Europe. The prognostic factors of pediatric AML were analyzed,and patients with AML were classified according to prognostic factors. The t(15;17), inv(16) and t(8;21) have emerged as predictors of good prognosis in children with AML. Monosomy 7, monosomy 5 and del (5 q) abnormalities showed a poor prognosis. In addition to chromosomal deletions, FLT 3/ITD identifies pediatric patients with a particularly poor prognosis. Clinical trials of AML feature intensive chemotherapy with or without subsequent stem cell transplantation. Risk group stratification is becoming increasingly important in planning AML therapy. APL can be distinguished from other subtypes of AML by virtue of its excellent response and overall outcome as a result of differentiation therapy with ATRA. Children with Down syndrome and AML have been shown to have a superior prognosis to AML therapy compared to other children with AML. The results of the Japan Cooperative Study Group protocol ANLL 91 was one of the best previously reported in the literature. With the consideration of quality of life (QOL), risk-adapted therapy was introduced in the AML 99 trial conducted by the Japanese Childhood AML Cooperative Study Group. A high survival rate of 79% at 3 years was achieved for childhood de novo AML in the AML 99 trial. To evaluate the efficacy and safety of the treatment strategy according to risk stratification based on leukemia cell biology and response to the initial induction therapy in children with AML, the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) has organized multi-center phase II trials in children with newly diagnosed AML.

  13. Electronic fraud (cyber fraud risk in the banking industry, Zimbabwe

    Directory of Open Access Journals (Sweden)

    Shewangu Dzomira

    2014-06-01

    Full Text Available The paper explores forms of electronic fraud which are being perpetrated in the banking industry and the challenges being faced in an attempt to combat the risk. The paper is based on a descriptive study which studied the cyber fraud phenomenon using content analysis. To obtain the data questionnaires and interviews were administered to the selected informants from 22 banks. Convenience and judgemental sampling techniques were used. It was found out that most of the cited types of electronic fraud are perpetrated across the banking industry. Challenges like lack of resources (detection tools and technologies, inadequate cyber-crime laws and lack of knowledge through education and awareness were noted. It is recommended that the issue of cyber security should be addressed involving all the stakeholders so that technological systems are safeguarded from cyber-attacks

  14. Current strategies for the diagnosis and management of chronic lymphocytic leukemia (CLL, with a focus on poor-risk CLL: A review

    Directory of Open Access Journals (Sweden)

    Fabienne Mc Clanahan

    2011-06-01

    Full Text Available Despite substantial advancement in the understanding and treatment of chronic lymphocytic leukemia (CLL, a standard curative approach does not exist. The choice of treatment is generally based on the existence of biological and genetic factors associated with the prediction of prognosis, individual response to therapy, and duration of remission. About 20% of patients that require treatment have an aggressive disease course and die within a few years, despite early initiation of intensive therapy (poor-risk CLL. Poor-risk CLL can be predicted by the presence of genomic markers, and the quality and duration of response to purine-analogue-based treatment. Within this patient subgroup alternative treatment approaches such as alemtuzumab or new substances such as flavopiridol or IMiDs® should be considered. To date, the only treatment bearing curative potential is allogeneic stem cell transplantation; in contrast to conventional immunochemotherapy, it can provide long-term disease control, even in patients with del 17p or other unfavorable biological and clinical risk factors. The aim of this review was to outline the current strategies for the diagnosis and management of CLL, with a focus on high-risk CLL.

  15. Current strategies for the diagnosis and management of chronic lymphocytic leukemia (CLL), with a focus on poor-risk CLL: A review.

    Science.gov (United States)

    Clanahan, Fabienne Mc; Dreger, Peter

    2011-06-05

    Despite substantial advancement in the understanding and treatment of chronic lymphocytic leukemia (CLL), a standard curative approach does not exist. The choice of treatment is generally based on the existence of biological and genetic factors associated with the prediction of prognosis, individual response to therapy, and duration of remission. About 20% of patients that require treatment have an aggressive disease course and die within a few years, despite early initiation of intensive therapy (poor-risk CLL). Poor-risk CLL can be predicted by the presence of genomic markers, and the quality and duration of response to purine-analogue-based treatment. Within this patient subgroup alternative treatment approaches such as alemtuzumab or new substances such as flavopiridol or IMiDs® should be considered. To date, the only treatment bearing curative potential is allogeneic stem cell transplantation; in contrast to conventional immunochemotherapy, it can provide long-term disease control, even in patients with del 17p or other unfavorable biological and clinical risk factors. The aim of this review was to outline the current strategies for the diagnosis and management of CLL, with a focus on high-risk CLL.

  16. Exposure to pesticides as risk factor for non-Hodgkin's lymphoma and hairy cell leukemia: pooled analysis of two Swedish case-control studies.

    Science.gov (United States)

    Hardell, Lennart; Eriksson, Mikael; Nordstrom, Marie

    2002-05-01

    Increased risk for non-Hodgkin's lymphoma (NHL) following exposure to certain pesticides has previously been reported. To further elucidate the importance of phenoxyacetic acids and other pesticides in the etiology of NHL a pooled analysis was performed on two case-control studies, one on NHL and another on hairy cell leukemia (HCL), a rare subtype of NHL. The studies were population based with cases identified from cancer registry and controls from population registry. Data assessment was ascertained by questionnaires supplemented over the telephone by specially trained interviewers. The pooled analysis of NHL and HCL was based on 515 cases and 1141 controls. Increased risks in univariate analysis were found for subjects exposed to herbicides (OR 1.75, CI 95% 1.26-2.42), insecticides (OR 1.43, CI 95% 1.08-1.87), fungicides (OR 3.11, CI 95% 1.56-6.27) and impregnating agents (OR 1.48, CI 95% 1.11-1.96). Among herbicides, significant associations were found for glyphosate (OR 3.04, CI 95% 1.08-8.52) and 4-chloro-2-methyl phenoxyacetic acid (MCPA) (OR 2.62, CI 95% 1.40-4.88). For several categories of pesticides the highest risk was found for exposure during the latest decades before diagnosis. However, in multivariate analyses the only significantly increased risk was for a heterogeneous category of other herbicides than above.

  17. Thrombocytopenia in leukemia: Pathogenesis and prognosis.

    Science.gov (United States)

    Shahrabi, Saeid; Behzad, Masumeh Maleki; Jaseb, Kaveh; Saki, Najmaldin

    2018-02-20

    Leukemias, a heterogeneous group of hematological disorders, are characterized by ineffective hematopoiesis and morphologic abnormalities of hematopoietic cells. Thrombocytopenia is a common problem among leukemia types that can lead to hemorrhagic complications in patients. The purpose of this review article is to identify the conditions associated with the incidence of thrombocytopenia in leukemias. It can be stated that although translocations have been considered responsible for this complication in many studies, other factors such as bone marrow failure, genes polymorphism, a mutation in some transcription factors, and the adverse effects of treatment could be associated with pathogenesis and poor prognosis of thrombocytopenia in leukemias. Considering the importance of thrombocytopenia in leukemias, it is hoped that the recognition of risk factors increasing the incidence of this complication in leukemic patients would be useful for prevention and treatment of this disorder.

  18. Leukemia in Nagasaki atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Brill, A B; Heyssel, R; Itoga, T; Tomonaga, M

    1960-08-01

    In the 13.5 years following the detonation of the atomic bomb, 95 cases of leukemia have been observed in the Nagasaki survivors. This increase is highly significant statistically. The increased leukemia risk apparently started 1.5 to 2.5 years following radiation exposure, and has lasted through 1958. Acute leukemias of all types and chronic granulocytic leukemia are increased, (with the possible exception of the Schilling type of acute monocytic leukemia). Males in general, and individuals in the younger ages (0 to 09), are apparently most sensitive. The risk of radiation induction of leukemia is related to the size of the dose. The shape of the curve does not differ greatly from a linear model, but is consistent with a variety of hypotheses. The data in the low dose region are too limited to be of significance in evaluating the risk of low doses of radiation. The data suggest that high radiation doses may be associated with a decrease in the latent period to leukemia induction. 43 references, 2 figures, 31 tables.

  19. [Establishment of Primary Adult MDS Nested Case-Control Study Cohort and Study of Risk Factors Associated with MDS Evolution to Leukemia].

    Science.gov (United States)

    Ma, Yan; Chen, Bo-Bin; Wang, Xiao-Qin; Xu, Xiao-Ping; Lin, Guo-Wei

    2015-12-01

    To establish a nested case-control study cohort in myelodysplastic syndrome (MDS) patients and investigate the clinical characteristics, WHO subtype and risk factors associated with MDS evolution to leukemia of this cohort. All patients, ≥18 years of age, provided by 24 Shanghai hospitals with initial clinical findings consistent with a hematopoietic abnormality between June 2003 and April 2007, were the candidates for inclusion in this study. The blood and bone marrow samples of every patient should be provided at baseline. Diagnosis was made by incorporating morphologic, immunophenotypic, cytogenetic and molecular features according to WHO classification criteria. Cytogenetic analysis was performed using conventional G-banding karyotyping and fluorescence in situ hybridization (FISH) techniques. Cumulative risk of evolution was estimated by Kaplan-Meier method. Prognostic factors were evaluated by univariate Log-rank method and multivariate Cox proportional hazard models. A total of 435 patients were diagnosed as MDS. The median age of MDS onset was 58(18-90) years, with 248 male patients and 187 female patients (male: female 1.33: 1). The percentage of cases with refractory cytopenia with multilineage dysplasia (RCMD) was the highest (65.5%), while that of refraetory anemia (RA) (2.3%), refractory anenia with ring sideroblast (RARS) (1.1%) and 5q-syndrome (0.5%) was lower. Trisomy 8 (+8) was the most common chromosome abnormalities (71 cases, 12.7%). The mean follow-up time was 20.3 (4.2-57.1) months. Cases were patients with evolution by the end of follow-up, while controls were patients without evolution by that time. Case group included 41 patients and control group included 342 patients. Univariate analysis showed that the age, sex, WHO subtype, WBC count, absolute neutrophil count (ANC), IPSS cytogenetic subgroup, IPSS group and bone marrow blast percentage were significant risk factors for leukemia-free survival (LFS). Multivariate analysis of COX model

  20. Radiogenic leukemia revisited

    International Nuclear Information System (INIS)

    Moloney, W.C.

    1987-01-01

    Radiation-induced leukemia is considered to be similar to the de novo disease. However, following an analysis of clinical and hematological findings in leukemia occurring in irradiated cervical cancer patients, adult Japanese atomic-bomb survivors, and spondylitics treated with x-ray, striking differences were noted. Acute leukemias in cervical cancer patients and Japanese survivors were similar in type to acute de novo leukemias in adults. Cell types among spondylitics were very dissimilar; rare forms, eg, acute erythromyelocytic leukemia (AEL) and acute megakaryocytic leukemia, were increased. Pancytopenia occurred in 25 of 35 cases and erythromyelodysplastic disorders were noted in seven of 35 acute cases. The leukemias and myelodysplastic disorders closely resembled those occurring in patients treated with alkylating agents. This similarity suggests a common pathogenesis involving marrow stem cell injury and extra-medullary mediators of hematopoiesis. Investigation of early acute leukemias and myelodysplastic disorders with newer techniques may provide valuable insights into the pathogenesis of leukemia in humans

  1. Kelainan Hemostasis pada Leukemia

    Directory of Open Access Journals (Sweden)

    Zelly Dia Rofinda

    2012-09-01

    Full Text Available AbstrakLatar belakang: Leukemia adalah penyakit keganasan pada jaringan hematopoietik yang ditandai denganpenggantian elemen sumsum tulang normal oleh sel darah abnormal atau sel leukemik. Salah satu manifestasi klinisdari leukemia adalah perdarahan yang disebabkan oleh berbagai kelainan hemostasis.Kelainan hemostasis yang dapat terjadi pada leukemia berupa trombositopenia, disfungsi trombosit,koagulasi intravaskuler diseminata, defek protein koagulasi, fibrinolisis primer dan trombosis. Patogenesis danpatofosiologi kelainan hemostasis pada leukemia tersebut terjadi dengan berbagai mekanisme.Kata kunci: leukemia, kelainan hemostasisAbstractBackground: AbstractLeukemia is a malignancy of hematopoietic tissue which is characterized bysubstituted of bone marrow element with abnormal blood cell or leukemic cell. One of clinical manifestation ofleukemia is bleeding that is caused by several hemostasis disorders.Hemostasis disorders in leukemia such asthrombocytopenia, platelet dysfunction, disseminated intravascular coagulation, coagulation protein defect, primaryfibrinolysis and thrombosis. Pathogenesis and pathophysiology of thus hemostasis disorders in leukemia occur withdifferent mechanism.Keywords: leukemia, hemostasis disorder

  2. Comparative pharmacogenetic analysis of risk polymorphisms in Caucasian and Vietnamese children with acute lymphoblastic leukemia: prediction of therapeutic outcome?

    Science.gov (United States)

    Hoang, Phuong Thu Vu; Ambroise, Jérôme; Dekairelle, Anne-France; Durant, Jean-François; Butoescu, Valentina; Chi, Vu Luan Dang; Huynh, Nghia; Nguyen, Tan Binh; Robert, Annie; Vermylen, Christiane; Gala, Jean-Luc

    2015-03-01

    Acute lymphoblastic leukemia (ALL) is the most common of all paediatric cancers. Aside from predisposing to ALL, polymorphisms could also be associated with poor outcome. Indeed, genetic variations involved in drug metabolism could, at least partially, be responsible for heterogeneous responses to standardized leukemia treatments, hence requiring more personalized therapy. The aims of this study were to (a) to determine the prevalence of seven common genetic polymorphisms including those that affect the folate and/or thiopurine metabolic pathways, i.e. cyclin D1 (CCND1-G870A), γ-glutamyl hydrolase (GGH-C452T), methylenetetrahydrofolate reductase (MTHFR-C677T and MTHFR-A1298C), thymidylate synthase promoter (TYMS-TSER), thiopurine methyltransferase (TPMT*3A and TPMT*3C) and inosine triphosphate pyrophosphatase (ITPA-C94A), in Caucasian (n = 94, age Vietnamese (n = 141, age Vietnamese (P < 0.001 and P = 0.02, respectively). Compared with children with a low MGRS (≤ 3), those with a high MGRS (≥ 4) were 2.06 (95% CI = 1.01, 4.22; P = 0.04) times more likely to relapse. Adding MGRS into a multivariate Cox regression model with race/ethnicity and four clinical variables improved the predictive accuracy of the model (AUC from 0.682 to 0.709 at 24 months). Including MGRS into a clinical model improved the predictive accuracy of short and medium term prognosis, hence confirming the association between well determined pharmacogenotypes and outcome of paediatric ALL. Whether variants on other genes associated with folate metabolism can substantially improve the predictive value of current MGRS is not known but deserves further evaluation. © 2014 The British Pharmacological Society.

  3. The contribution of benzene to smoking-induced leukemia.

    OpenAIRE

    Korte, J E; Hertz-Picciotto, I; Schulz, M R; Ball, L M; Duell, E J

    2000-01-01

    Cigarette smoking is associated with an increased risk of leukemia; benzene, an established leukemogen, is present in cigarette smoke. By combining epidemiologic data on the health effects of smoking with risk assessment techniques for low-dose extrapolation, we assessed the proportion of smoking-induced total leukemia and acute myeloid leukemia (AML) attributable to the benzene in cigarette smoke. We fit both linear and quadratic models to data from two benzene-exposed occupational cohorts t...

  4. An intronic polymorphism of IRF4 gene influences gene transcription in vitro and shows a risk association with childhood acute lymphoblastic leukemia in males.

    Science.gov (United States)

    Do, Thuy N; Ucisik-Akkaya, Esma; Davis, Charronne F; Morrison, Brittany A; Dorak, M Tevfik

    2010-02-01

    The interferon regulatory factor (IRF) family of DNA-binding proteins regulates expression of interferon-inducible genes with roles in the immune response and carcinogenesis. IRF4 is involved in the differentiation of B and T cells and is overexpressed in B-cell malignancies as a result of c-REL (NF-kappaB) hyperactivation. IRF4 polymorphisms are associated with susceptibility to chronic lymphoid leukemia (CLL) and non-Hodgkin lymphoma (NHL). We examined 13 IRF4 SNPs in 114 cases of childhood acute lymphoblastic leukemia (ALL) and 388 newborn controls from Wales (U.K.) using TaqMan assays. IRF4 intron 4 SNP rs12203592 showed a male-specific risk association (OR=4.4, 95% CI=1.5 to 12.6, P=0.007). Functional consequences of the C>T substitution at this SNP were assessed by cell-based reporter assays using three different cell lines. We found a repressive effect of the rs12203592 wildtype allele C on IRF4 promoter activity (Pcell line tested. Thus, homozygosity for the rs12203592 variant allele would result in increased IRF4 expression. This increase would be compounded by high levels of NF-kappaB activity in males due to the absence of estrogen. IRF4 differs from other IRFs in its anti-interferon activity which interferes with immune surveillance. We propose that a detailed study of IRF4 can provide information on the mechanism of the sex effect and the role of immune surveillance in childhood ALL development. Copyright 2009 Elsevier B.V. All rights reserved.

  5. Epidemiological assessment of leukemia in Kazakhstan, 2003- 2012.

    Science.gov (United States)

    Igissinov, Nurbek; Kulmirzayeva, Dariyana; Moore, Malcolm A; Igissinov, Saginbek; Baidosova, Gulnara; Akpolatova, Gulnur; Bukeyeva, Zhanar; Omralina, Yelvira

    2014-01-01

    Cancer is a major health problem facing the entire world, and Kazakhstan is not the exception. The aim of this study was to present an epidemiological assessment of leukemia in the population of Kazakhstan during 2003-2012. This descriptive and retrospective study was based on data obtained from all oncological organizations of the whole country. Age standardized incidence rates per 100,000 population for leukemia were calculated. Totally, 6,741 new cases of leukemia were registered in Kazakhstan during the 10 year period. The mean age of patients with leukemia was 48.5. The ASRs for leukemia among men and women were 5.3 and 3.6, respectively (pKazakhstan, especially in the north of the country. The incidence of leukemia was significantly higher in males and increased with age. Determining and controlling important risk factors of leukemia may lead to decrease in its burden.

  6. Cancers other than leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Beebe, G W; Kato, H [Radiation Effects Research Foundation, Hiroshima (Japan)

    1975-09-01

    Cancers which are unlikely to appear among atomic bomb survirors in excess of natural incidence include skin cancer and bone cancer, as these appear to require for their initiation doses that are incompatible with life if administered on a whole body basis. Although chronic lymphocytic leukemia continues to provide an important exception, and for many sites of cancer there is not yet evidence that radiation has increased incidence above normal levels, the data on A-bomb survivors are otherwise consistent with the hypothesis that the carcinogenic effect of ionizing radiation is general, involving all tissues. Studies of cancer among A-bomb survivors are notably limited with respect to the influence of variables other than dose, age, sex, and time. It seems highly desirable that other risk factors be studied in conjunction with radiation dose and demographic variables in an effort to detect interactions that might provide clues as to the etiology of cancer and as to the mechanisms by which ionizing radiation produces cancer. Provisional estimates suggest that the absolute risk of cancer, in terms of excess cases per 10/sup 6/ person-year rads (T65 dose) are about 1.6 for leukemia, 1.2 for thyroid, 2.1 for breast and 2.0 for lung, when estimation is based on age-ATB groups that have demonstrated these effects.

  7. Risk group assignment differs for children and adults 1-45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol

    DEFF Research Database (Denmark)

    Toft, Nina; Birgens, Henrik; Abrahamsson, Jonas

    2013-01-01

    The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined.......The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined....

  8. Clinical trials of CCLSG L874 and I874 protocols without cranial irradiation for standard-risk acute lymphoblastic leukemia in childhood

    International Nuclear Information System (INIS)

    Koizumi, Shoichi; Fujimoto, Takeo; Tsurusawa, Masahito

    1992-01-01

    In the CCLSG-874 protocol for children with low-risk (LR) and intermediate-risk (IR) acute lymphoblastic leukemia (ALL), two regimens with or without cranial irradiation (CI) were compared with respect to their ability to prevent central nervous system (CNS) leukemia and to improve overall outcome of ALL. From 1987 to 1990, 82 and 109 evaluable patients were registered into L874 and I874 protocols for LR and IR patients, respectively. All responders to induction therapy were randomized to treatment with 18 Gy of CI plus intrathecal methotrexate (MTX it) or to treatment with high-dose MTX plus MTX it. Patients were then treated with standard maintenance regimens of L874 and I874. At a median follow-up of 39 months (range 14-58 months) there was no difference in the rate of hematologic relapse between the CI group and MTX group. The rate of CNS relapse in the MTX group seemed to be higher (3 of 39 in L874 and 2 of 54 in I874) than that in the CI group (1 of 43 in L874 and 0 of 55 in I874), but these data were not statistically significant. The rates of 4-year event-free survival (EFS) in L874 were 81.1±7.6% (mean±SE) and 75.2±7.9% (ns) for the CI and MTX group, respectively, and the rates of EFS in I874 were 70.0±13.6% and 70.0±9.0% (ns) for the CI and MTX group, respectively. These data suggest that MTX alone may be as effective as CI to prolong disease-free survival in LR and IR ALL although further continuous studies are needed. Analysis of serial CCLSG protocols for ALL from 1981 revealed that the rate of EFS of ALL allover including all risk groups has gradually been increasing from 44.2±3.6% for 811 protocol and 53.1±3.5% for 841 to 65.5±3.6% for the present 874 protocol. (author)

  9. The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse

    DEFF Research Database (Denmark)

    Schmiegelow, K; Donovan, Martin Heyman; Sherson, Maiken Gustafsson

    2010-01-01

    Drug doses, blood levels of drug metabolites and myelotoxicity during 6-mercaptopurine/methotrexate (MTX) maintenance therapy were registered for 59 adolescents (10 years) and 176 non-adolescents (leukemia (ALL) and a white blood cell count (WBC......) diagnosis. Event-free survival was lower for adolescents than non-adolescents (pEFS12y:0.71 vs 0.83, P=0.04). For adolescents staying in remission, the mean WBC during maintenance therapy (mWBC) was related to age (rS=0.36, P=0.02), which became nonsignificant for those who relapsed (r...

  10. Leukemia in Hiroshima atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Heyssel, R; Brill, A B; Woodbury, L A; Nishimura, Edwin T; Ghose, Tarunendu; Hoshino, Takashi; Yamasaki, Mitsuru

    1959-03-01

    This report is intended to provide the basic data pertinent to the leukemia experience observed in the survivors of the Hiroshima atomic explosion. Many of the conclusions in this report are tentative. The one clear fact to emerge is that radiation increases the occurrence rate of leukemia and that the magnitude of increase is dependent on dose received. Additional observations can be made, which, while not definitive in themselves, seem to complement each other, and are corroborated by other experiences in radiation biology. From the data a linear relationship between dose and incidence of leukemia is found. The shape of the relation in the lower dose range is not known with certainty. An approximate minimum time for the appearance of leukemia following radiation is 3 years or less. The data suggest that the time of maximum risk of leukemia may be dependent on the dose of radiation received. In this group the mean latent period is found to lie in the interval between 4 and 8 years following exposure. The length of time during which the increased incidence of leukemia persists is not known. The incidence of the acute leukemias and of chronic granulocytic leukemia is increased in the exposed survivors. The chronic granulocytic variety is disproportionately increased in Japanese survivors of the atomic bomb. No effect of radiation on monocytic or chronic lymphatic leukemia incidence is noted. Aplastic anemia, polycythemia vera, and myelofibrosis have been investigated. Myelofibrosis is the only one of this group of diseases in which a suggestive relation to radiation exposure is apparent. The natural history of leukemia following radiation does not seem to differ from that of the spontaneously occurring variety. 17 references, 5 figures, 38 tables.

  11. Severe neutropenia at time of port insertion is not a risk factor for catheter-associated infections in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Junqueira, Beatriz L P; Connolly, Bairbre; Abla, Oussama; Tomlinson, George; Amaral, Joao G

    2010-09-15

    The objective of this study was to determine whether severe neutropenia on the day of port-a-catheter (PORT) insertion was a risk factor for catheter-associated infection (CAI) in children with acute lymphoblastic leukemia (ALL). This was a retrospective study of children with ALL who had a PORT insertion between January 2005 and August 2008. Early (≤ 30 days) and late (>30 days) postprocedure complications were reviewed. The length of follow-up ranged between 7 months and 42 months. In total, 192 PORTs were inserted in 179 children. There were 43 CAIs (22%), and the infection rate was 0.35 per 1000 catheter-days. The CAI rate (15%) in children who had severe neutropenia on the day of the procedure did not differ statistically from the CAI rate (24%) in children who did not have severe neutropenia (P = .137). Conversely, patients with severe neutropenia who had a CAI were more likely to have their PORT removed (P = .019). The most common organisms to cause catheter removal were coagulase-negative Staphylococcus and Staphylococcus aureus. Patients with high-risk ALL had a statistically significant higher incidence of late CAI than patients with standard-risk ALL (P = .012). Age (P = .272), positive blood culture preprocedure (P = 1.0), and dexamethasone use (P = .201) were not risk factors for CAI. Patients who had an early CAI did not have a greater chance of having a late CAI. The catheter infection-free survival rate at 1 year was 88.6%. The current results indicated that severe neutropenia on the day of PORT insertion does not increase the risk of CAI in children with ALL. © 2010 American Cancer Society.

  12. Reanalysis of atomic bomb survivors' leukemia based on the recent classification for leukemias

    International Nuclear Information System (INIS)

    Matsuo, Tatsuki; Tomonaga, Masao.

    1990-01-01

    Four hundred and ninety-three A-bomb survivors developing leukemia, who had been exposed within 9,000 m from the hypocenter, were entered on the study for reanalysis of their disease based on the new classification. Chronic myelocytic leukemia (CML) showed the highest concordance rate (95%) between the previous and new classifications. For 10 survivors previously diagnosed as having chronic lymphocytic leukemia (CLL), a new classification diagnosed CLL as well in 3 and adult T-cell leukemia in the other 7. None of the A-bomb survivors exposed to one Gy or more had subtype M3 of acute myelocytic leukemia (AML), although the exposed group had almost the same distribution pattern of AML subtypes as the naturally induced leukemic group. The incidence of CML was significantly lower than that of AML in Nagasaki A-bomb survivors. As A-bomb survivors were older at the time of A-bombing, the relative risk of acute lymphoblastic leukemia (ALL) was decreased; that of CML and other types of leukemia was increased. An increased relative risk of ALL and CML tended to be associated with larger doses. A significantly shortened interval between A-bomb exposure and the development of leukemia was also associated with larger doses. (N.K.)

  13. Acute Lymphocytic Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

  14. Acute Myeloid Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

  15. Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  16. Chronic Myeloid Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  17. Chronic lymphocytic leukemia (CLL)

    Science.gov (United States)

    ... is used for painful and enlarged lymph nodes. Blood transfusions or platelet transfusions may be required if blood ... unexplained fatigue, bruising, excessive sweating, or weight loss. Alternative ... Leukemia - chronic lymphocytic (CLL); Blood cancer - chronic lymphocytic leukemia; Bone marrow cancer - chronic ...

  18. Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia-positive chronic myeloid leukemia: a European LeukemiaNet Study

    DEFF Research Database (Denmark)

    Baccarani, Michele; Rosti, Gianantonio; Castagnetti, Fausto

    2009-01-01

    Imatinib mesylate (IM), 400 mg daily, is the standard treatment of Philadelphia-positive (Ph(+)) chronic myeloid leukemia (CML). Preclinical data and results of single-arm studies raised the suggestion that better results could be achieved with a higher dose. To investigate whether the systematic...

  19. Influence of IL15 gene variations on the clinical features, treatment response and risk of developing childhood acute lymphoblastic leukemia in Latvian population.

    Science.gov (United States)

    Rots, Dmitrijs; Kreile, Madara; Nikulshin, Sergejs; Kovalova, Zhanna; Gailite, Linda

    2018-02-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Modern treatment protocols allow achievement of long-term event-free survival rates in up to 85% of cases, although the treatment response varies among different patient groups. It is hypothesized that treatment response is influenced by the IL15 gene variations, although research results are conflicting. To analyze IL15 gene variations influence treatment response, clinical course and the risk of developing ALL we performed a case-control and family-based study. The study included 81 patients with childhood ALL. DNA samples of both or one biological parent were available for 62 of ALL patients and 130 age and gender adjusted healthy samples were used as a control group. Analyzed IL15 gene variations: rs10519612, rs10519613 and rs17007695 were genotyped using PCR-RFLP assay. Our results shows that IL15 gene variations haplotypes are associated with the risk of developing childhood ALL (p variations separately. The variations rs10519612 and rs1059613 in a recessive pattern of inheritance were associated with hyperdiploidy (p = 0.048). Analyzed genetic variations had no impact on other clinical features and treatment response (assessed by the minimal residual disease) in our study.

  20. Monitoring minimal residual disease in children with high-risk relapses of acute lymphoblastic leukemia: prognostic relevance of early and late assessment.

    Science.gov (United States)

    Eckert, C; Hagedorn, N; Sramkova, L; Mann, G; Panzer-Grümayer, R; Peters, C; Bourquin, J-P; Klingebiel, T; Borkhardt, A; Cario, G; Alten, J; Escherich, G; Astrahantseff, K; Seeger, K; Henze, G; von Stackelberg, A

    2015-08-01

    The prognosis for children with high-risk relapsed acute lymphoblastic leukemia (ALL) is poor. Here, we assessed the prognostic importance of response during induction and consolidation treatment prior to hematopoietic stem cell transplantation (HSCT) aiming to evaluate the best time to assess minimal residual disease (MRD) for intervention strategies and in future trials in high-risk ALL relapse patients. Included patients (n=125) were treated uniformly according to the ALL-REZ BFM (Berlin-Frankfurt-Münster) 2002 relapse trial (median follow-up time=4.8 years). Patients with MRD ⩾10(-3) after induction treatment (76/119, 64%) or immediately preceding HSCT (19/71, 27%) had a significantly worse probability of disease-free survival 10 years after relapse treatment begin, with 26% (±6%) or 23% (±7%), respectively, compared with 58% (±8%) or 48% (±7%) for patients with MRD treatment reduced MRD to treatment can be used to quantify the activity of different induction treatment strategies in phase II trials. MRD persistence at ⩾10(-3) before HSCT reflects a disease highly resistant to conventional intensive chemotherapy and requiring prospective controlled investigation of new treatment strategies and drugs.

  1. Do polymorphisms in MDR1 and CYP3A5 genes influence the risk of cytogenetic relapse in patients with chronic myeloid leukemia on imatinib therapy?

    Science.gov (United States)

    Harivenkatesh, Natarajan; Kumar, Lalit; Bakhshi, Sameer; Sharma, Atul; Kabra, Madhulika; Velpandian, Thirumurthy; Gogia, Ajay; Shastri, Shivaram S; Gupta, Yogendra Kumar

    2017-09-01

    Influence of polymorphisms in the genes coding for imatinib transporters and metabolizing enzymes on cytogenetic relapse in patients with chronic myeloid leukemia (CML) is not known. One hundred and four patients (52 cases with cytogenetic relapse and 52 controls without relapse) with chronic-phase CML on imatinib therapy and have completed 5 years of follow-up were enrolled. The following single nucleotide polymorphisms (SNPs) were genotyped; C1236T, C3435T, G2677T/A in MDR1 gene and A6986G in CYP3A5 gene, using PCR-RFLP method and validated by direct gene sequencing. Imatinib trough levels were measured using LC-MS/MS. Patients with CC genotype for MDR1-C1236T polymorphism were at significantly higher risk for cytogenetic relapse [OR =4.382, 95% CI (1.145, 16.774), p = .022], while those with TT genotype for MDR1-C3435T polymorphism had significantly lower risk of relapse [OR =0.309, 95% CI (0.134, 0.708), p = .005]. Imatinib trough levels were lower in patients with relapse compared to those without relapse (1551.4 ± 1324.1 vs. 2154.2 ± 1358.3 ng/mL; p = .041). MDR1-C3435T genotype [adjusted-OR: 0.266; 95% CI (0.111, 0.636); p = .003] and trough levels (p = .014) were independent predictors of relapse in multivariate analysis. To conclude, C1236T and C3435T polymorphisms in MDR1 gene and trough levels significantly influence the risk of cytogenetic relapse. MDR1-C3435T genotype might emerge as a potential biomarker to predict the risk of cytogenetic relapse in patients with CML.

  2. Chronic neutrophilic leukemia.

    Science.gov (United States)

    Bredeweg, Arthur; Burch, Micah; Krause, John R

    2018-01-01

    Chronic neutrophilic leukemia is a rare myeloproliferative disorder characterized by a sustained peripheral blood neutrophilia, absence of the BCR/ABL oncoprotein, bone marrow hypercellularity with less than 5% myeloblasts and normal neutrophil maturation, and no dysplasia. This leukemia has been associated with mutations in the colony-stimulating factor 3 receptor (CSF3R) that may activate this receptor, leading to the proliferation of neutrophils that are the hallmark of chronic neutrophilic leukemia. We present a case of chronic neutrophilic leukemia and discuss the criteria for diagnosis and the significance of mutations found in this leukemia.

  3. ePORT, NASA's Computer Database Program for System Safety Risk Management Oversight (Electronic Project Online Risk Tool)

    Science.gov (United States)

    Johnson, Paul W.

    2008-01-01

    ePORT (electronic Project Online Risk Tool) provides a systematic approach to using an electronic database program to manage a program/project risk management processes. This presentation will briefly cover the standard risk management procedures, then thoroughly cover NASA's Risk Management tool called ePORT. This electronic Project Online Risk Tool (ePORT) is a web-based risk management program that provides a common framework to capture and manage risks, independent of a programs/projects size and budget. It is used to thoroughly cover the risk management paradigm providing standardized evaluation criterion for common management reporting, ePORT improves Product Line, Center and Corporate Management insight, simplifies program/project manager reporting, and maintains an archive of data for historical reference.

  4. Long-term Follow-up of Treatment with Ibrutinib and Rituximab in Patients with High-Risk Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Jain, Preetesh; Keating, Michael J; Wierda, William G; Sivina, Mariela; Thompson, Philip A; Ferrajoli, Alessandra; Estrov, Zeev; Kantarjian, Hagop; O'Brien, Susan; Burger, Jan A

    2017-05-01

    Background: Ibrutinib is an active therapy with an acceptable safety profile for patients with chronic lymphocytic leukemia (CLL), including high-risk patients with del17p or with TP53 mutations. Ibrutinib is broadly indicated for the treatment of patients with CLL and specifically including those with 17p deletion. The optimal use of ibrutinib in combination with other agents remains controversial. Experimental Design: We report the long-term outcome [median follow-up of 47 months (range, 36-51 months)] of 40 patients with high-risk CLL, treated on the first ibrutinib combination trial with rituximab (IR). The majority of patients (36/40) were previously treated. Results: Median age was 65 years, and 21 patients (52%) had 17p deletion. Median duration on treatment was 41 months (range, 2-51 months), and median number of treatment cycles was 42 (range, 2-49). Overall response rate was 95%, and 9 patients (23%) attained a complete remission. Twenty-one patients discontinued treatment, 10 due to disease progression, 9 for other causes, and 2 due to stem cell transplantation; the remaining 19 patients continue on ibrutinib. Median progression-free survival for all patients was 45 months, which was significantly shorter in the subgroup of patients with del17p ( n = 21, 32.3 months, P = 0.02). Fourteen patients (35%) died, five from progressive disease, five from infections, and four from other causes. Median overall survival has not been reached. Conclusions: IR combination therapy leads to durable remissions in high-risk CLL; the possible benefit from the addition of rituximab is currently explored in a randomized trial. Clin Cancer Res; 23(9); 2154-8. ©2016 AACR . ©2016 American Association for Cancer Research.

  5. Multilineage dysplasia is associated with a poorer prognosis in patients with de novo acute myeloid leukemia with intermediate-risk cytogenetics and wild-type NPM1.

    Science.gov (United States)

    Rozman, María; Navarro, José-Tomás; Arenillas, Leonor; Aventín, Anna; Giménez, Teresa; Alonso, Esther; Perea, Granada; Camós, Mireia; Navarrete, Mayda; Tuset, Esperanza; Florensa, Lourdes; Millá, Fuensanta; Nomdedéu, Josep; de la Banda, Esmeralda; Díaz-Beyá, Marina; Pratcorona, Marta; Garrido, Ana; Navarro, Blanca; Brunet, Salut; Sierra, Jorge; Esteve, Jordi

    2014-10-01

    Acute myeloid leukemia (AML) with myelodysplasia-related changes is characterized by the presence of multilineage dysplasia (MLD), frequently related to high-risk cytogenetics and poor outcome. However, the presence of MLD does not modify the favorable prognostic impact of NPM1 mutation. The prognosis of patients with AML presenting marked dysplasia lacking high-risk cytogenetics and NPM1 mutation is uncertain. We evaluated the prognostic impact of MLD in 177 patients with intermediate-risk cytogenetics AML (IR-AML) and wild-type NPM1. Patients were categorized as MLD-WHO (WHO myelodysplasia criteria; n = 43, 24 %), MLD-NRW (significant MLD non-reaching WHO criteria; n = 16, 9 %), absent MLD (n = 80, 45 %), or non-evaluable MLD (n = 38, 22 %). No differences concerning the main characteristics were observed between patients with or without MLD. Outcome of patients with MLD-WHO and MLD-NRW was similar, and significantly worse than patients lacking MLD. The presence of MLD (66 vs. 80 %, p = 0.03; HR, 95 % CI = 2.3, 1.08-4.08) and higher leukocyte count at diagnosis was the only variable associated with lower probability of complete remission after frontline therapy. Concerning survival, age and leukocytes showed an independent prognostic value, whereas MLD showed a trend to a negative impact (p = 0.087, HR, 95 % CI = 1.426, 0.95-2.142). Moreover, after excluding patients receiving an allogeneic stem cell transplantation in first CR, MLD was associated with a shorter survival (HR, 95 % CI = 1.599, 1.026-2.492; p = 0.038). In conclusion, MLD identifies a subgroup of patients with poorer outcome among patients with IR-AML and wild-type NPM1.

  6. Health-related quality of life in lower-risk MDS patients compared with age- and sex-matched reference populations: a European LeukemiaNet study.

    Science.gov (United States)

    Stauder, Reinhard; Yu, Ge; Koinig, Karin A; Bagguley, Tim; Fenaux, Pierre; Symeonidis, Argiris; Sanz, Guillermo; Cermak, Jaroslav; Mittelman, Moshe; Hellström-Lindberg, Eva; Langemeijer, Saskia; Holm, Mette Skov; Mądry, Krzysztof; Malcovati, Luca; Tatic, Aurelia; Germing, Ulrich; Savic, Aleksandar; van Marrewijk, Corine; Guerci-Bresler, Agnès; Luño, Elisa; Droste, Jackie; Efficace, Fabio; Smith, Alex; Bowen, David; de Witte, Theo

    2018-03-06

    In myelodysplastic syndromes (MDS), health-related quality of life (HRQoL) represents a relevant patient-reported outcome, which is essential in individualized therapy planning. Prospective data on HRQoL in lower-risk MDS remain rare. We assessed HRQOL by EQ-5D questionnaire at initial diagnosis in 1690 consecutive IPSS-Low/Int-1 MDS patients from the European LeukemiaNet Registry. Impairments were compared with age- and sex-matched EuroQol Group norms. A significant proportion of MDS patients reported moderate/severe problems in the dimensions pain/discomfort (49.5%), mobility (41.0%), anxiety/depression (37.9%), and usual activities (36.1%). Limitations in mobility, self-care, usual activities, pain/discomfort, and EQ-VAS were significantly more frequent in the old, in females, and in those with high co-morbidity burden, low haemoglobin levels, or red blood cells transfusion need (p MDS patients (p MDS-related restrictions in the dimension mobility were most prominent in males, and in older people (p MDS experience a pronounced reduction in HRQoL and a clustering of restrictions in distinct dimensions of HRQoL as compared with reference populations.

  7. Outcome of children with high-risk acute myeloid leukemia given autologous or allogeneic hematopoietic cell transplantation in the aieop AML-2002/01 study.

    Science.gov (United States)

    Locatelli, F; Masetti, R; Rondelli, R; Zecca, M; Fagioli, F; Rovelli, A; Messina, C; Lanino, E; Bertaina, A; Favre, C; Giorgiani, G; Ripaldi, M; Ziino, O; Palumbo, G; Pillon, M; Pession, A; Rutella, S; Prete, A

    2015-02-01

    We analyzed the outcome of 243 children with high-risk (HR) AML in first CR1 enrolled in the AIEOP-2002/01 protocol, who were given either allogeneic (ALLO; n=141) or autologous (AUTO; n=102) hematopoietic SCT (HSCT), depending on the availability of a HLA-compatible sibling. Infants, patients with AML-M7, or complex karyotype or those with FLT3-ITD, were eligible to be transplanted also from alternative donors. All patients received a myeloablative regimen combining busulfan, cyclophosphamide and melphalan; [corrected] AUTO-HSCT patients received BM cells in most cases, while in children given ALLO-HSCT stem cell source was BM in 96, peripheral blood in 19 and cord blood in 26. With a median follow-up of 57 months (range 12-130), the probability of disease-free survival (DFS) was 73% and 63% in patients given either ALLO- or AUTO-HSCT, respectively (P=NS). Although the cumulative incidence (CI) of relapse was lower in ALLO- than in AUTO-HSCT recipients (17% vs 28%, respectively; P=0.043), the CI of TRM was 7% in both groups. Patients transplanted with unrelated donor cord blood had a remarkable 92.3% 8-year DFS probability. Altogether, these data confirm that HSCT is a suitable option for preventing leukemia recurrence in HR children with CR1 AML.

  8. The biology and targeting of FLT3 in pediatric leukemia

    Directory of Open Access Journals (Sweden)

    Colleen eAnnesley

    2014-09-01

    Full Text Available Despite remarkable improvement in treatment outcomes in pediatric leukemia over the past several decades, the prognosis for high risk groups of acute myeloid leukemia (AML and acute lymphoblastic leukemia (ALL, as well as for relapsed leukemia, remains poor. Intensified chemotherapy regimens have somewhat improved success rates, but at the cost of drastically increased morbidity and long term adverse effects. With the success of imatinib in Philadelphia-chromosome positive leukemia and all-trans retinoic acid in acute promyelocytic leukemia, the quest to find additional molecularly targeted therapies has generated much excitement over the past 15 years. Another such possible target in pediatric acute leukemia is FMS-like tyrosine kinase 3 (FLT3. FLT3 aberrations are among the most frequently identified transforming events in AML, and have significant clinical implications in both high risk pediatric AML and in certain high risk groups of pediatric ALL. Therefore, the successful targeting of FLT3 has tremendous potential to improve outcomes in these subsets of patients. This article will give an overview of the molecular function and signaling of the FLT3 receptor, as well as its pathogenic role in leukemia. We review the discovery of targeting FLT3, discuss currently available FLT3 inhibitors in pediatric leukemia and results of clinical trials to date, and finally, consider the future promise and challenges of FLT3 inhibitor therapy.

  9. Prognostic significance of P2RY8-CRLF2 and CRLF2 overexpression may vary across risk subgroups of childhood B-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Dou, Hu; Chen, Xi; Huang, Yi; Su, Yongchun; Lu, Ling; Yu, Jie; Yin, Yibing; Bao, Liming

    2017-02-01

    The cytokine receptor-like factor 2 (CRLF2) gene plays an important role in early B-cell development. Aberrations in CRLF2 activate the JAK-STAT signaling pathway that contributes to B-cell acute lymphoblastic leukemia (B-ALL). The prognostic significance of CRLF2 overexpression and P2RY8-CRLF2 fusion in various B-ALL risk subgroups has not been well established. Two hundred seventy-one patients with newly diagnosed childhood B-ALL were enrolled from a Chinese population. The prevalence of CRLF2 overexpression, CRLF2-P2RY8 fusion, CRLF2 F232C mutation, and JAK2 and IL7R mutational status were analyzed, and the prognostic impact of CRLF2 overexpression and P2RY8-CRLF2 on B-ALL was evaluated by assessing their influence on overall survival and event-free survival. CRLF2 overexpression and P2RY8-CRLF2 were found in 19% and 10%, respectively, in the whole cohort. No correlation between CRLF2 overexpression and P2RY8-CRLF2 was observed. CRLF2 F322C and IL7R mutations were not detected in B-ALL cases overexpressing CRLF2, and no JAK2 mutations were found in the whole cohort either. The results showed that CRLF2 overexpression and P2RY8-CRLF2 were associated with a poor outcome in unselected B-ALL. Moreover, in an intermediate risk B-ALL subgroup P2RY8-CRLF2 was correlated with worse survival, whereas in high- and low-risk subgroups, CRLF2 overexpression predicted a poor outcome. Our findings suggest that P2RY8-CRLF2 is an independent prognostic indicator in intermediate risk B-ALL, while CRLF2 overexpression is correlated with an inferior outcome in high- or low-risk B-ALL. Our study demonstrates that the impact of P2RY8-CRLF2 and CRLF2 overexpression on B-ALL survival may differ across risk subgroups. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. [Management of the cardiovascular disease risk during nilotinib treatment in chronic myeloid leukemia: 2015 recommendations from the France Intergroupe des Leucémies Myéloïdes Chroniques].

    Science.gov (United States)

    Rea, Delphine; Ame, Shanti; Charbonnier, Aude; Coiteux, Valérie; Cony-Makhoul, Pascale; Escoffre-Barbe, Martine; Etienne, Gabriel; Gardembas, Martine; Guerci-Bresler, Agnès; Legros, Laurence; Nicolini, Franck; Tulliez, Michel; Hermet, Eric; Huguet, Françoise; Johnson-Ansah, Hyacinthe; Lapusan, Simona; Quittet, Philippe; Rousselot, Philippe; Mahon, François-Xavier; Messas, Emmanuel

    2016-02-01

    Tyrosine kinase inhibitors targeting the BCR-ABL oncoprotein represent an outstanding progress in chronic myeloid leukemia and long-term progression-free survival has become a reality for a majority of patients. However, tyrosine kinase inhibitors may at best chronicize rather than cure the disease thus current recommendation is to pursue treatment indefinitely. As a consequence, high quality treatment and care must integrate optimal disease control and treatment tolerability. Tyrosine kinase inhibitors have an overall favorable safety profile in clinical practice since most adverse events are mild to moderate in intensity. However, recent evidence has emerged that new generation tyrosine kinase inhibitors may sometimes damage vital organs and if not adequately managed, morbidity and mortality may increase. The 2nd generation tyrosine kinase inhibitor nilotinib is licensed for the treatment of chronic myeloid leukemia with resistance or intolerance to imatinib and newly diagnosed chronic phase-chronic myeloid leukemia. Nilotinib represents an important therapeutic option but it is associated with an increased risk of cardiovascular events. The purpose of this article by the France Intergroupe des Leucémies Myéloïdes Chroniques is to provide an overview of nilotinib efficacy and cardiovascular safety profile and to propose practical recommendations with the goal to minimize the risk and severity of cardiovascular events in nilotinib-treated patients. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  11. [Comparison of the present and previously used protocol of risk stratification in children with acute lymphoblastic leukemia].

    Science.gov (United States)

    Glodkowska, Eliza; Bialas, Agnieszka; Jackowska, Teresa

    2007-01-01

    Acute lymphoblastic leukaemia (ALL) is one of the most common cancers in children. In Poland, since November 2002 a new protocol of risk stratification has been recommended for assessment of risk factors and for choosing therapy regimens. assessment of accuracy of protocol ALL-IC 2002 in comparison to previously used risk stratification protocols. ALL was diagnosed in 100 children (44 girls, 56 boys; 1-18 years of age) in the Department of Pediatric Hematology and Oncology, Warsaw Medical University, over the period from November 2002 to November 2006. According to the ALL-IC 2002 protocol the patients were divided into three risk groups: SR-standard, IR-intermediate and HR-high. The stratification was by age, leukocyte count, cytogenetic changes, early response to prednisone therapy and bone marrow remission. In the previously used risk stratification protocols-BFM-90, only hepatosplenomegaly and the number of blasts in peripheral blood (PB) were considered, and the patients were divided into three risk groups: low (LRG1.2). out of the 100 patients qualified for treatment regimens according to the ALL-IC 2002 protocol, 97 entered remission, 11 died and 3 had a relapse. Under the ALL-IC 2002 protocol these children were stratified into the following groups: SR-31%, IR-44% and HR-25%. In the previously used stratification, there would be 26% children in low, 46% in the medium and 28% in the high risk group. According to the BFM-90 protocol 18/31 (58%) and 16/44 (36%) patients from the SR and IR groups respectively would be given more intensive treatment. On the other hand 11/44 (25%) and 14/25 (56%) patients from the IR and HR groups respectively would be given less intensive treatment. 1. ALL-IC 2002 protocol in comparison with the previously used protocol BFM-90, changes the qualification of children with ALL for the SR, IR and HR risk groups. This is linked to basic change of treatment protocol, adequate to severity of disease. 2. Children with ALL qualified

  12. Comparison of risk factors for seropositivity to feline immunodeficiency virus and feline leukemia virus among cats: a case-case study.

    Science.gov (United States)

    Chhetri, Bimal K; Berke, Olaf; Pearl, David L; Bienzle, Dorothee

    2015-02-10

    Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are reported to have similar risk factors and similar recommendations apply to manage infected cats. However, some contrasting evidence exists in the literature with regard to commonly reported risk factors. In this study, we investigated whether the known risk factors for FIV and FeLV infections have a stronger effect for either infection. This retrospective study included samples from 696 cats seropositive for FIV and 593 cats seropositive for FeLV from the United States and Canada. Data were collected during two cross sectional studies, where cats were tested using IDEXX FIV/FeLV ELISA kits. To compare the effect of known risk factors for FIV infection compared to FeLV, using a case-case study design, random intercept logistic regression models were fit including cats' age, sex, neuter status, outdoor exposure, health status and type of testing facility as independent variables. A random intercept for testing facility was included to account for clustering expected in testing practices at the individual clinics and shelters. In the multivariable random intercept model, the odds of FIV compared to FeLV positive ELISA results were greater for adults (OR = 2.09, CI: 1.50-2.92), intact males (OR = 3.14, CI: 1.85-3.76), neutered males (OR = 2.68, CI: 1.44- 3.14), cats with outdoor access (OR = 2.58, CI: 1.85-3.76) and lower for cats with clinical illness (OR = 0.60, 95% CI: 0.52-0.90). The variance components obtained from the model indicated clustering at the testing facility level. Risk factors that have a greater effect on FIV seropositivity include adulthood, being male (neutered or not) and having access to outdoors, while clinical illness was a stronger predictor for FeLV seropositivity. Further studies are warranted to assess the implications of these results for the management and control of these infections.

  13. Leukemia after therapy with alkylating agents for childhood cancer

    International Nuclear Information System (INIS)

    Tucker, M.A.; Meadows, A.T.; Boice, J.D. Jr.

    1987-01-01

    The risk of leukemia was evaluated in 9,170 2-or-more-year survivors of childhood cancer in the 13 institutions of the Late Effects Study Group. Secondary leukemia occurred in 22 nonreferred individuals compared to 1.52 expected, based on general population rates [relative risk (RR) = 14; 95% confidence interval (CI), 9-22]. The influence of therapy for the first cancer on subsequent leukemia risk was determined by a case-control study conducted on 25 cases and 90 matched controls. Treatment with alkylating agents was associated with a significantly elevated risk of leukemia (RR = 4.8; 95% CI, 1.2-18.9). A strong dose-response relationship was also observed between leukemia risk and total dose of alkylating agents, estimated by an alkylator score. The RR of leukemia reached 23 in the highest dose category. Radiation therapy, however, did not increase risk. Although doxorubicin was also identified as a possible risk factor, the excess risk of leukemia following treatment for childhood cancer appears almost entirely due to alkylating agents

  14. What You Need to Know about Leukemia

    Science.gov (United States)

    ... Publications Reports What You Need To Know About™ Leukemia This booklet is about leukemia. Leukemia is cancer of the blood and bone marrow ( ... This book covers: Basics about blood cells and leukemia Types of doctors who treat leukemia Treatments for ...

  15. Oral methotrexate/6-mercaptopurine may be superior to a multidrug LSA2L2 Maintenance therapy for higher risk childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Heyman, Mats; Kristinsson, Jon

    2009-01-01

    The importance of maintenance therapy for higher risk childhood acute lymphoblastic leukemia (ALL) is uncertain. Between 1992 and 2001 the Nordic Society for Pediatric Haematology/Oncology compared in a nonrandomized study conventional oral methotrexate (MTX)/6-mercaptopurine (6MP) maintenance...... therapy (P=0.04) were both related to an increased risk of an event (overall P value of the Cox model: 0.003), whereas neither sex, age at diagnosis, administration of central nervous system irradiation, nor presence of a day 15 bone marrow with > or =25% versus

  16. 76 FR 3075 - Availability of an Environmental Assessment for Field Testing Feline Leukemia Vaccine, Live...

    Science.gov (United States)

    2011-01-19

    ...] Availability of an Environmental Assessment for Field Testing Feline Leukemia Vaccine, Live Canarypox Vector... Feline Leukemia Vaccine, Live Canarypox Vector. The environmental assessment, which is based on a risk... ADDRESSES above for a link to Regulations.gov ). Requester: Merial, Inc. Product: Feline Leukemia Vaccine...

  17. Osteogenesis imperfecta and acute lymphoid leukemia: case report

    Directory of Open Access Journals (Sweden)

    Gabriel David Tarud

    2017-08-01

    Discussion: It is well described that genetic and chromosomal abnormalities increase the risk of leukemia, however the relationship between osteogenesis imperfecta and acute lymphoblastic leukemia is rare. In the world literature, there are few cases mentioning this association. It is important to continue observing the occurrence of later cases, which allow describing if there is a direct relationship between these two entities.

  18. Integrated methodology for production related risk management of vehicle electronics (IMPROVE)

    OpenAIRE

    Geis, Stefan Rafael

    2006-01-01

    This scientific work is designated to provide an innovative and integrated conceptional approach to improve the assembly quality of automotive electronics. This is achieved by the reduction and elimination of production related risks of automotive electronics and the implementation of a sustainable solution process. The focus is the development and implementation of an integrated technical risk management approach for automotive electronics throughout the vehicle life cycle and the vehicle pr...

  19. Radioinduced leukemia. An introduction to the study of experimental leukemia in mice

    International Nuclear Information System (INIS)

    Baudon, P.P.

    1974-01-01

    This thesis attempts to gain insight into any mechanisms involved in the onset of irradiation-induced leukemia in mice, then to show up the presence of a virus in the same animals. Concerning the mechanisms of radio-induced leukemias the pathogenic factors according to Kaplan are analysed: role of the thymus and cell mutation theory; lymphoid leukemias of extra-thymic origin; leukemogenesis co-factor; inhibiting action of the bone narrow. Evidence of the virus in mice was obtained by the use of electron microscopy, by inoculation. The contribution of experimental leukemia research is analysed, especially as it affects the therapeutic aspect. It is shown that in spite of setbacks in the most recent research on man, therapeutic trials on animals should be viewed from the angle of imminent human applications [fr

  20. Murine and human leukemias.

    Science.gov (United States)

    Burchenal, J H

    1975-01-01

    Essentially all the drugs which are active against human leukemias and lymphomas are active against one type or another of the rodent leukemias and lymphomas. Leukemia L1210 has been generally the most successful screening tool for clinically active compounds. Leukemia P388, however, seems to be better in detecting active antibiotics and natural products and P1534 is particularly sensitive to the Vinca alkaloids, while L5178Y, EARAD, and 6C3HED are useful in detecting the activities of various asparaginase containing fractions. Cell cultures of these leukemias can demonstrate mechanism of drug action and quantitate resistance. Spontaneous AKR leukemia is a model of the advanced human disease. In these leukemias vincristine and prednisone produce a 4 log cell kill. Cytoxan and arabinosyl cytosine (Ara-C) are also effective. On the other hand drugs such as mercaptopurine (6MP) and methotrexate which are highly active in the maintenance phase of acute lymphocytic leukemia (ALL) and in L1210 have little or no activity against the AKR spontaneous system. Mouse leukemias can also detect schedule dependence, synergistic combinations, cross resistance, oral activity, and the ability of drugs to pass the blood brain barrier. A case in point is the Ara-C analog 2,2'-anhydro-arabinofuranosyl-5-fluorocytosine (AAFC) which is not schedule dependent, is active orally, is potentiated by thioguanine, and is effective against intracerebrally inoculated mouse leukemia. AAFC and its analogs might thus be a considerable improvement over Ara-C which is at the present time the most important component of the combination treatment of acute myelogenous leukemia (AML).

  1. Leukemia in Hiroshima atomic bomb survivors from 1946 to 1975

    International Nuclear Information System (INIS)

    Ohkita, Takeshi

    1976-01-01

    In five recent years, 134 deaths from leukemia among Hiroshima citizen were recorded. Of these, 23 cases (17 acute and 6 chronic types) were atomic bomb survivors exposed within 2,000 m of the hypocenter. Fifteen of them (65%) were over 60 years of age. The frequency of chronic lymphocytic leukemia was still low. Although the risk of leukemia was greatly reduced after 1961, and the frequency of chronic granulocytic leukemia (one of the most characteristic type of Hiroshima atomic bomb-induced leukemia) was also decreased, the death rate from leukemia among survivors exposed within 2,000 m or 1,500 m from the hypocenter was about 3 to 4 times higher than the mean death rate in all Japan. Therefore, careful and long-range follow-up surveillance should be continued. A brief review was also made of relevant studies such as the influence of environmental and host factors in the epidemiology of leukemia, the incidence of leukemia in children exposed in utero, and leukemia in offspring of atomic bomb survivors. (Evans, J.)

  2. The incidence of leukemia, lymphoma, and multiple myeloma among atomic bomb survivors: 1950 – 2001

    Science.gov (United States)

    Hsu, Wan-Ling; Preston, Dale L.; Soda, Midori; Sugiyama, Hiromi; Funamoto, Sachiyo; Kodama, Kazunori; Kimura, Akiro; Kamada, Nanao; Dohy, Hiroo; Tomonaga, Masao; Iwanaga, Masako; Miyazaki, Yasushi; Cullings, Harry M.; Suyama, Akihiko; Ozasa, Kotaro; Shore, Roy E.; Mabuchi, Kiyohiko

    2013-01-01

    A marked increase in leukemia risks was the first and most striking late effect of radiation exposure seen among the Hiroshima and Nagasaki atomic bomb survivors. This paper presents analyses of radiation effects on leukemia, lymphoma, and multiple myeloma incidence in the Life Span Study cohort of atomic bomb survivors updated 14 years since the last comprehensive report on these malignancies. These analyses make use of tumor- and leukemia-registry-based incidence data on 113,011 cohort members with 3.6 million person-years of follow-up from late 1950 through the end of 2001. In addition to a detailed analysis of the excess risk for all leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia (neither of which appear to be radiation-related), we present results for the major hematopoietic malignancy types: acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, chronic myeloid leukemia, adult T-cell leukemia, Hodgkin and non-Hodgkin lymphoma, and multiple myeloma. Poisson regression methods were used to characterize the shape of the radiation dose response relationship and, to the extent the data allowed, to investigate variation in the excess risks with sex, attained age, exposure age, and time since exposure. In contrast to the previous report that focused on describing excess absolute rates, we considered both excess absolute rate (EAR) and excess relative risk (ERR) models and found that ERR models can often provide equivalent and sometimes more parsimonious descriptions of the excess risk than EAR models. The leukemia results indicated that there was a non-linear dose response for leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia, which varied markedly with time and age at exposure, with much of the evidence for this non-linearity arising from the acute myeloid leukemia risks. Although the leukemia excess risks generally declined with attained age or time since exposure, there was evidence

  3. Macroglobulinemia in a child with acute leukemia

    NARCIS (Netherlands)

    Cejka, J.; Bollinger, R.O.; Schuit, H.R.E.; Lusher, J.M.; Chang, C.H.; Zuelzer, W.W.

    1974-01-01

    A 12-yr-old boy with acute leukemia was found to have paraproteinemia and Bence-Jones proteinuria. The paraprotein was characterized as immunoglobulin M, type κ and the Bence Jones protein as free κ-chains. Increased amounts of β2-microglobulin were found in the patient’s serum and urine. Electron

  4. Atomic bomb and leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Ichimaru, M; Tomonaga, M; Amenomori, T; Matsuo, T [Nagasaki Univ. (Japan). School of Medicine

    1991-12-01

    Characteristic features of the leukemia among atomic bomb survivors were studied. Dose estimates of atomic bomb radiation were based on T65D, but the new dosimetry system DS86 was used for some analyses. The ratio of a single leukemia type to all leukemias was highest for chronic myelogenous leukemia (CML) in Hiroshima, and the occurrence of CML was thought to be most characteristic to atomic bomb radiation induced leukemia. The threshold of CML occurrence in Hiroshima is likely to be between 0.5{approx}0.09 Gy. However, the threshold of acute leukemia appears to be nearly 1 Gy. In the distribution of acute myeloid leukemia (AML) subtypes by French-American-British classification, there was no M3 case in 1 Gy or more group, although several atypical AML cases of survivors were observed. Although aplastic anemia has not increased as a late effect of the atomic bomb radiation exposure, many atypical leukemia or other myeloproliferative diseases who had been diagnosed as aplastic anemia or its related diseases have been experienced among atomic bomb survivors. Chromosome study was conducted using colony forming cells induced by hemopoietic stem cells of peripheral blood of proximal survivors. Same chromosome aberrations were observed in colony forming cells and peripheral T-cells in several atomic bomb survivors. (author).

  5. Atomic bomb and leukemia

    International Nuclear Information System (INIS)

    Ichimaru, M.; Tomonaga, M.; Amenomori, T.; Matsuo, T.

    1991-01-01

    Characteristic features of the leukemia among atomic bomb survivors were studied. Dose estimates of atomic bomb radiation were based on T65D, but the new dosimetry system DS86 was used for some analyses. The ratio of a single leukemia type to all leukemias was highest for chronic myelogenous leukemia (CML) in Hiroshima, and the occurrence of CML was thought to be most characteristic to atomic bomb radiation induced leukemia. The threshold of CML occurrence in Hiroshima is likely to be between 0.5∼0.09 Gy. However, the threshold of acute leukemia appears to be nearly 1 Gy. In the distribution of acute myeloid leukemia (AML) subtypes by French-American-British classification, there was no M3 case in 1 Gy or more group, although several atypical AML cases of survivors were observed. Although aplastic anemia has not increased as a late effect of the atomic bomb radiation exposure, many atypical leukemia or other myeloproliferative diseases who had been diagnosed as aplastic anemia or its related diseases have been experienced among atomic bomb survivors. Chromosome study was conducted using colony forming cells induced by hemopoietic stem cells of peripheral blood of proximal survivors. Same chromosome aberrations were observed in colony forming cells and peripheral T-cells in several atomic bomb survivors. (author)

  6. Experimental studies of leukemia

    International Nuclear Information System (INIS)

    Yokoro, Kenjiro

    1977-01-01

    Mouse leukemia, especially the relationship between that and endogenous type-C RNA virus (murine leukemia virus, MLV), was generally discussed centering around the recent findings and reports. Correlation of carcinogenesis due to x-rays and carcinogens with the occurrence of MLV, the relationship of total body fractionated x-ray irradiation and successive acellular transmission by the neonatal inoculation with MLV, and the relationship between N-nitrosobutylurea or N-nitrosoethylurea and MLV were discussed. The relationship between the occurrence of MLV and thymus or spleen was also discussed. Biotic differences in mice and rats, the relationship between MLV the organotropism of MLV and provocation of leukemia, the directivity of MLV to thymus and the etiologic correlation of rat leukemia or mouse leukemia with MLV were mentioned. (Ichikawa, K.)

  7. Resveratrol given intraperitoneally does not inhibit growth of high-risk t(4;11) acute lymphoblastic leukemia cells in NOD/SCID mouse model

    Science.gov (United States)

    The efficacy of the phytochemical resveratrol as a preventive agent against the growth of t(4;11) acute lymphoblastic leukemia (ALL) was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) ALL line SEM. SEM cells were injected into the tail vein and engraftment was monitored by ...

  8. Cytomorphology review of 100 newly diagnosed lower-risk MDS patients in the European LeukemiaNet MDS (EUMDS) registry reveals a high inter-observer concordance

    NARCIS (Netherlands)

    Swart, L. de; Smith, A.; MacKenzie, M.; Symeonidis, A.; Neukirchen, J.; Mikulenkova, D.; Vallespi, T.; Zini, G.; Paszkowska-Kowalewska, M.; Kruger, A.; Saft, L.; Fenaux, P.; Bowen, D.; Hellstrom-Lindberg, E.; Cermak, J.; Stauder, R.; Tatic, A.; Holm, M.S.; Malcovati, L.; Madry, K.; Droste, J.A.; Blijlevens, N.M.; Witte, T.J. de; Germing, U.

    2017-01-01

    The European LeukemiaNet MDS (EUMDS) registry is collecting data of myelodysplastic syndrome (MDS) patients belonging to the IPSS low or intermediate-1 category, newly diagnosed by local cytologists. The diagnosis of MDS can be challenging, and some data report inter-observer variability with regard

  9. Perspectives on the causes of childhood leukemia.

    Science.gov (United States)

    Wiemels, Joseph

    2012-04-05

    Acute leukemia is the most common cancer in children but the causes of the disease in the majority of cases are not known. About 80% are precursor-B cell in origin (CD19+, CD10+), and this immunophenotype has increased in incidence over the past several decades in the Western world. Part of this increase may be due to the introduction of new chemical exposures into the child's environment including parental smoking, pesticides, traffic fumes, paint and household chemicals. However, much of the increase in leukemia rates is likely linked to altered patterns of infection during early childhood development, mirroring causal pathways responsible for a similarly increased incidence of other childhood-diagnosed immune-related illnesses including allergy, asthma, and type 1 diabetes. Factors linked to childhood leukemia that are likely surrogates for immune stimulation include exposure to childcare settings, parity status and birth order, vaccination history, and population mixing. In case-control studies, acute lymphoblastic leukemia (ALL) is consistently inversely associated with greater exposure to infections, via daycare and later birth order. New evidence suggests also that children who contract leukemia may harbor a congenital defect in immune responder status, as indicated by lower levels of the immunosuppressive cytokine IL-10 at birth in children who grow up to contract leukemia, as well as higher need for clinical care for infections within the first year of life despite having lower levels of exposure to infections. One manifestation of this phenomenon may be leukemia clusters which tend to appear as a leukemia "outbreak" among populations with low herd immunity to a new infection. Critical answers to the etiology of childhood leukemia will require incorporating new tools into traditional epidemiologic approaches - including the classification of leukemia at a molecular scale, better exposure assessments at all points in a child's life, a comprehensive

  10. Infective endocarditis and risk of death after cardiac implantable electronic device implantation

    DEFF Research Database (Denmark)

    Özcan, Cengiz; Raunsø, Jakob; Lamberts, Morten

    2017-01-01

    AIMS: To determine the incidence, risk factors, and mortality of infective endocarditis (IE) following implantation of a first-time, permanent, cardiac implantable electronic device (CIED). METHODS AND RESULTS: From Danish nationwide administrative registers (beginning in 1996), we identified all...

  11. Progress in the leukemias

    International Nuclear Information System (INIS)

    Galton, D.A.G.; Spiers, A.S.D.

    1971-01-01

    Recent work on the epidemiology of leukemia is reviewed in relation to factors of possible etiologic importance. There is still much geographic variation in the accuracy of diagnosis, the reliability of death certification, and the provision of national registries for classifying leukemia according to cytologic type. This variation and the low incidence of all types of leukemia make difficult the recognition of potentially significant distributions or trends that might suggest the operation of environmental leukemogens and their interaction with genetically determined susceptibility. Exposure to ionizing radiation remains the only predisposing factor beyond doubt for acute and chronic granulocytic leukemia, but its exact role remains obscure. There is no evidence that radiation plays a part in the etiology of chronic lymphocytic leukemia. In the population of survivors of the Hiroshima atomic bomb explosion of 1945, the incidence of leukemia (mainly CGL), though declining in the second 10-year period, was still higher than that of Japan as a whole. The suggestion that the exposure of women to radiation could increase the likelihood of leukemia in their still unconceived children was examined by the Atomic Bomb Casualty Commission in a prospective study of 17,700 children, and no increase in the incidence of leukemia was found in the children of parents who had been heavily exposed to radiation before conception. In the 1960's a decline in the United States mortality rates for leukemia among the white population was recorded. This decline was most marked in children below age 5, and it was suggested that the decline could have resulted from a drop in the use of diagnostic radiology in pregnant women following the reports in 1956 of the Medical Research Council and the National Academy of Sciences on the biologic hazards of radiation. A similar decline in mortality was reported from Norway. (464 references) (U.S.)

  12. Brick mortar exposure and chronic lymphocytic leukemia.

    Science.gov (United States)

    Markovic-Denic, L; Jankovic, S; Marinkovic, J; Radovanovic, Z

    1995-01-01

    A case-control study of 130 patients with chronic lymphocytic leukemia (CLL) and 130 controls matched with respect to sex, age (2 years), type of residence (urban-rural) and area of residence (according to the national per capita income) was carried out. Conditional logistic regression analysis showed that, apart of four risk factors already described in the literature (work in a hazardous industry, hair dye use, family history of leukemia and exposure to electromagnetic radiation), brick mortar exposure was also significantly related to CLL.

  13. Brick mortar exposure and chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Markovic-Denic, Lj.; Jankovic, S.; Marinkovic, J.; Radovanovic, Z.

    1995-01-01

    A case-control study of 130 patients with chronic lymphocytic leukemia (CLL) and 130 controls matched with respect to sex, age (2 years), type of residence, (urban-rural) and area of residence (according to the national per capita income) was carried out. Conditional logistic regression analysis showed that, apart of four risk factors already described in the literature (work in a hazardous industry, hair dye use, family history of leukemia and exposure to electromagnetic radiation), brick mortar exposure was also significantly related to CLL. (author)

  14. Brick mortar exposure and chronic lymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Markovic-Denic, Lj; Jankovic, S [Institute of Epidemiology, Faculty of Medicine, Belgrade (Yugoslavia); Marinkovic, J [Institute of Social Medicine, Statistics and Healt Research, Faculty of Medicine, Belgrade (Yugoslavia); Radovanovic, Z [Department of Community Medicine and Behavioural Sciences, Faculty of Medicine, 13110 Safat (Kuwait)

    1996-12-31

    A case-control study of 130 patients with chronic lymphocytic leukemia (CLL) and 130 controls matched with respect to sex, age (2 years), type of residence, (urban-rural) and area of residence (according to the national per capita income) was carried out. Conditional logistic regression analysis showed that, apart of four risk factors already described in the literature (work in a hazardous industry, hair dye use, family history of leukemia and exposure to electromagnetic radiation), brick mortar exposure was also significantly related to CLL. (author) 1 tab., 30 refs.

  15. The MLL recombinome of acute leukemias in 2013

    DEFF Research Database (Denmark)

    Meyer, C; Hofmann, Julian; Burmeister, T

    2013-01-01

    patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79......Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia...... patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All...

  16. Identification and Progression of Heart Disease Risk Factors in Diabetic Patients from Longitudinal Electronic Health Records

    Directory of Open Access Journals (Sweden)

    Jitendra Jonnagaddala

    2015-01-01

    Full Text Available Heart disease is the leading cause of death worldwide. Therefore, assessing the risk of its occurrence is a crucial step in predicting serious cardiac events. Identifying heart disease risk factors and tracking their progression is a preliminary step in heart disease risk assessment. A large number of studies have reported the use of risk factor data collected prospectively. Electronic health record systems are a great resource of the required risk factor data. Unfortunately, most of the valuable information on risk factor data is buried in the form of unstructured clinical notes in electronic health records. In this study, we present an information extraction system to extract related information on heart disease risk factors from unstructured clinical notes using a hybrid approach. The hybrid approach employs both machine learning and rule-based clinical text mining techniques. The developed system achieved an overall microaveraged F-score of 0.8302.

  17. Leukemia and ionizing radiation revisited

    Energy Technology Data Exchange (ETDEWEB)

    Cuttler, J.M. [Cuttler & Associates Inc., Vaughan, Ontario (Canada); Welsh, J.S. [Loyola University-Chicago, Dept. or Radiation Oncology, Stritch School of Medicine, Maywood, Illinois (United States)

    2016-03-15

    A world-wide radiation health scare was created in the late 19508 to stop the testing of atomic bombs and block the development of nuclear energy. In spite of the large amount of evidence that contradicts the cancer predictions, this fear continues. It impairs the use of low radiation doses in medical diagnostic imaging and radiation therapy. This brief article revisits the second of two key studies, which revolutionized radiation protection, and identifies a serious error that was missed. This error in analyzing the leukemia incidence among the 195,000 survivors, in the combined exposed populations of Hiroshima and Nagasaki, invalidates use of the LNT model for assessing the risk of cancer from ionizing radiation. The threshold acute dose for radiation-induced leukemia, based on about 96,800 humans, is identified to be about 50 rem, or 0.5 Sv. It is reasonable to expect that the thresholds for other cancer types are higher than this level. No predictions or hints of excess cancer risk (or any other health risk) should be made for an acute exposure below this value until there is scientific evidence to support the LNT hypothesis. (author)

  18. Drugs Approved for Leukemia

    Science.gov (United States)

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  19. Acute lymphoblastic leukemia (ALL)

    Science.gov (United States)

    ... better. Most children with ALL can be cured. Children often have a better outcome than adults. ... Both leukemia itself and the treatment can lead to many problems such as bleeding, weight loss, and infections.

  20. Current strategies for the diagnosis and management of chronic lymphocytic leukemia (CLL), with a focus on poor-risk CLL: A review

    OpenAIRE

    Fabienne Mc Clanahan; Peter Dreger

    2011-01-01

    Despite substantial advancement in the understanding and treatment of chronic lymphocytic leukemia (CLL), a standard curative approach does not exist. The choice of treatment is generally based on the existence of biological and genetic factors associated with the prediction of prognosis, individual response to therapy, and duration of remission. About 20% of patients that require treatment have an aggressive disease course and die within a few years, despite early initiation of intensive the...

  1. Cardiac implantable electronic device and associated risk of infective endocarditis in patients undergoing aortic valve replacement

    DEFF Research Database (Denmark)

    Østergaard, Lauge; Valeur, Nana; Bundgaard, Henning

    2017-01-01

    Aims: Patients undergoing aortic valve replacement (AVR) are at increased risk of infective endocarditis (IE) as are patients with a cardiac implantable electronic device (CIED). However, few data exist on the IE risk after AVR surgery in patients with a CIED. Methods and results: Using the Danish...

  2. The Risk of Electronic Audit and its Impact on The Quality Audit

    Directory of Open Access Journals (Sweden)

    Zainab Jabbar Yousif

    2018-05-01

    Full Text Available The auditing profession faces a challenge referred to as information technology ,Information technology has set the profession of auditing in constant challenge because it has made the world an open - limited system through communication technology . The importance of this research stems from the need to identify the nature of the  risks of electronic auditing  after turned  from manual checking to electronic auditing due to developments in technologies  in all sectors.  The risk of electronic auditing  the risk of information technology infrastructure and the risks of applications and other  related to communication processes, several conclusions have been reached, implementation of programs with goods specifications in the electronic auditing  process will lead to safety of work and  reduce the risk of electronic auditing . The research highlights these  risks and their impact on the quality of auditing .                                  

  3. Homozygous HLA-C1 is Associated with Reduced Risk of Relapse after HLA-Matched Transplantation in Patients with Myeloid Leukemia.

    Science.gov (United States)

    Arima, Nobuyoshi; Kanda, Junya; Tanaka, Junji; Yabe, Toshio; Morishima, Yasuo; Kim, Sung-Won; Najima, Yuho; Ozawa, Yukiyasu; Eto, Tetsuya; Kanamori, Heiwa; Mori, Takehiko; Kobayashi, Naoki; Kondo, Tadakazu; Nakamae, Hirohisa; Uchida, Naoyuki; Inoue, Masami; Fukuda, Takahiro; Ichinohe, Tatsuo; Atsuta, Yoshiko; Kanda, Yoshinobu

    2018-04-01

    Natural killer (NK) cells assume graft-versus-leukemia alloreactivity after hematopoietic stem cell transplantation (HSCT) through their inhibitory killer cell immunoglobulin-like receptors (KIRs). KIR2D family members recognize HLA-C alleles with Asn80 (HLA-C1) or Lys80 (HLA-C2). The predominance of HLA-C1 over HLA-C2 and the frequent presence of KIR2DL1 are characteristic of Japanese people. We compared clinical outcomes among homozygous HLA-C1 (HLA-C1/C1) patients and heterozygous HLA-C1/C2 patients who underwent HLA-matched HSCT for hematologic malignancies by assessing the data of 10,638 patients from the Japanese national registry. HLA-C1/C1 recipients had a lower rate of relapse than HLA-C1/C2 recipients after transplantation for acute myelogenous leukemia (AML) (hazard ratio [HR], .79; P = .006) and chronic myelogenous leukemia (CML) (HR, .48; P = .025), but not for acute lymphoblastic leukemia (HR, 1.36), lymphoma (HR, .97), or low-grade myelodysplastic syndrome (HR, 1.40). We then grouped AML and CML patients together and divided them into several subgroups. Advantages of HLA-C1/C1 recipients over HLA-C1/C2 recipients regarding relapse were observed irrespective of donor relation (related: HR, .79, P = .069; unrelated: HR, .77, P = .022), preparative regimen (myeloablative: HR, .79, P = .014; reduced intensity: HR, .73, P = .084), and occurrence of acute graft-versus-host disease (yes: HR, .70, P = .122; no, HR .71, P = .026) or cytomegalovirus reactivation (reactivated: HR .67,P = .054; nonreactivated: HR .71, P = .033); however, these advantages were not observed in recipients with a delay in achieving complete chimerism (HR, 1.06). The advantage of decreasing relapse and extending relapse-free survival of C1/1 over C1/2 KIR-ligand status was most pronounced in T cell-depleted HSCT (HR, .27; P < .001 and HR, .30; P = .002, respectively) and in children age <15 years (HR, .29; P < .001 and HR .31; P

  4. The Structural Characterisation of Risk in the R&D Process of Functional Raw Materials for Electronic Devices

    OpenAIRE

    Chikamori, Yoji; Nasu, Seigo

    2017-01-01

    The electronic materials and electronics device industries remain important to Japan in spite of the general decline of the Japanese electronics industry. There is risk and uncertainty when developing functional materials in the electronics industry. However, studies examining the uncertainty and risk variables in the development of functional materials are scarce. This study examines incremental research and development (R&D) developed for raw functional materials for electronics. Our analys...

  5. Cost-effectiveness of electronic training in domestic violence risk assessment: ODARA 101.

    Science.gov (United States)

    Hilton, N Zoe; Ham, Elke

    2015-03-01

    The need for domestic violence training has increased with the development of evidence-based risk assessment tools, which must be scored correctly for valid application. Emerging research indicates that training in domestic violence risk assessment can increase scoring accuracy, but despite the increasing popularity of electronic training, it is not yet known whether it can be an effective method of risk assessment training. In the present study, 87 assessors from various professions had training in the Ontario Domestic Assault Risk Assessment either face-to-face or using an electronic training program. The two conditions were equally effective, as measured by performance on a post-training skill acquisition test. Completion rates were 100% for face-to-face and 86% for electronic training, an improvement over a previously evaluated manual-only condition. The estimated per-trainee cost of electronic training was one third that of face-to-face training and expected to decrease. More rigorous evaluations of electronic training for risk assessment are recommended. © The Author(s) 2014.

  6. Acute myeloid leukemia (AML) - children

    Science.gov (United States)

    Acute myeloid leukemia is a cancer of the blood and bone marrow. Bone marrow is the soft tissue inside ... develops quickly. Both adults and children can get acute myeloid leukemia ( AML ). This article is about AML in children.

  7. Inheritance of leukemia in humans

    International Nuclear Information System (INIS)

    Kamada, Nanao

    1991-01-01

    Since Gardner et al. reported an increased incidence of leukemia among children of workers of a nuclear reactor in Sellafield, UK, there have been a number of discussions on the possibility of increased incidence of leukemia among children born from parents exposed to radiation or chemical agents. In this present paper, apart from the leukemia incidence in children from atomic bomb survivors which was discussed by Dr. Yoshimoto, familial leukemia, i.e., a cluster of leukemia among family members within four genetic relations, was discussed with special reference to the age distribution, type of leukemia and consanguinity. Leukemia in twin and leukemias in individuals with congenital anomalies with or without chromosome abnormalities were also discussed. (author)

  8. Stages of Chronic Myelogenous Leukemia

    Science.gov (United States)

    ... ALL Treatment Childhood AML Treatment Research Chronic Myelogenous Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Myelogenous Leukemia Go to Health Professional Version Key Points Chronic ...

  9. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial.

    Science.gov (United States)

    Dreger, Peter; Döhner, Hartmut; Ritgen, Matthias; Böttcher, Sebastian; Busch, Raymonde; Dietrich, Sascha; Bunjes, Donald; Cohen, Sandra; Schubert, Jörg; Hegenbart, Ute; Beelen, Dietrich; Zeis, Matthias; Stadler, Michael; Hasenkamp, Justin; Uharek, Lutz; Scheid, Christof; Humpe, Andreas; Zenz, Thorsten; Winkler, Dirk; Hallek, Michael; Kneba, Michael; Schmitz, Norbert; Stilgenbauer, Stephan

    2010-10-07

    The purpose of this prospective multicenter phase 2 trial was to investigate the long-term outcome of reduced-intensity conditioning allogeneic stem cell transplantation (alloSCT) in patients with poor-risk chronic lymphocytic leukemia. Conditioning was fludarabine/ cyclophosphamide-based. Longitudinal quantitative monitoring of minimal residual disease (MRD) was performed centrally by MRD-flow or real-time quantitative polymerase chain reaction. One hundred eligible patients were enrolled, and 90 patients proceeded to alloSCT. With a median follow-up of 46 months (7-102 months), 4-year nonrelapse mortality, event-free survival (EFS) and overall survival (OS) were 23%, 42%, and 65%, respectively. Of 52 patients with MRD monitoring available, 27 (52%) were alive and MRD negative at 12 months after transplant. Four-year EFS of this subset was 89% with all event-free patients except for 2 being MRD negative at the most recent assessment. EFS was similar for all genetic subsets, including 17p deletion (17p-). In multivariate analyses, uncontrolled disease at alloSCT and in vivo T-cell depletion with alemtuzumab, but not 17p-, previous purine analogue refractoriness, or donor source (human leukocyte antigen-identical siblings or unrelated donors) had an adverse impact on EFS and OS. In conclusion, alloSCT for poor-risk chronic lymphocytic leukemia can result in long-term MRD-negative survival in up to one-half of the patients independent of the underlying genomic risk profile. This trial is registered at http://clinicaltrials.gov as NCT00281983.

  10. Occupation and leukemia: a population-based case-control study in Iowa and Minnesota.

    Science.gov (United States)

    Blair, A; Zheng, T; Linos, A; Stewart, P A; Zhang, Y W; Cantor, K P

    2001-07-01

    Studies have suggested that risk of leukemia may be associated with occupational or industrial exposures and risk may vary by the histological type of the disease. A population-based case-control study was conducted in Iowa and Minnesota to evaluate the association between various occupations, industries, and occupational exposures and leukemia risk. A total of 513 cases and 1,087 controls was included in the study. A lifetime occupational history and other risk factor information were collected through in-person interviews, and a job-exposure matrix was used to assess possible risks associated with specific exposures. A significantly increased risk of leukemia was observed among agricultural service industries and among nursing and healthcare workers. Janitors, cleaners, and light truck drivers also experienced increased risk. Those employed in plumbing, heating and air conditioning industries, and sales of nondurable goods (such as paints and varnishes) had an increased risk. Printers, painters, and workers in the food and metal industries had a nonsignificantly increased risk of leukemia. Analyses by specific exposures and histology of leukemia showed that risk of leukemia associated with occupational or industrial exposures may vary by histological type of the disease. An increased risk of leukemia among workers employed in agricultural industries, nursing and healthcare workers, and in a few occupations with possible exposure to solvents is consistent with earlier studies. Associations of risk with occupations not observed previously deserve further assessment. Published 2001 Wiley-Liss, Inc.

  11. A Bayesian network model for predicting type 2 diabetes risk based on electronic health records

    Science.gov (United States)

    Xie, Jiang; Liu, Yan; Zeng, Xu; Zhang, Wu; Mei, Zhen

    2017-07-01

    An extensive, in-depth study of diabetes risk factors (DBRF) is of crucial importance to prevent (or reduce) the chance of suffering from type 2 diabetes (T2D). Accumulation of electronic health records (EHRs) makes it possible to build nonlinear relationships between risk factors and diabetes. However, the current DBRF researches mainly focus on qualitative analyses, and the inconformity of physical examination items makes the risk factors likely to be lost, which drives us to study the novel machine learning approach for risk model development. In this paper, we use Bayesian networks (BNs) to analyze the relationship between physical examination information and T2D, and to quantify the link between risk factors and T2D. Furthermore, with the quantitative analyses of DBRF, we adopt EHR and propose a machine learning approach based on BNs to predict the risk of T2D. The experiments demonstrate that our approach can lead to better predictive performance than the classical risk model.

  12. Molecular biomarkers for the study of childhood leukemia

    International Nuclear Information System (INIS)

    Smith, Martyn T.; McHale, Cliona M.; Wiemels, Joseph L.; Zhang, Luoping; Wiencke, John K.; Zheng, Shichun; Gunn, Laura; Skibola, Christine F.; Ma, Xiaomei; Buffler, Patricia A.

    2005-01-01

    Various specific chromosome rearrangements, including t(8;21), t(15;17), and inv(16), are found in acute myeloid leukemia (AML) and in childhood acute lymphocytic leukemia (ALL), t(12;21) and t(1;19) are common. We sequenced the translocation breakpoints of 56 patients with childhood ALL or AML harboring t(12;21), t(8;21), t(15;17), inv(16), and t(1;19), and demonstrated, with the notable exception of t(1;19), that these rearrangements are commonly detected in the neonatal blood spots (Guthrie cards) of the cases. These findings show that most childhood leukemias begin before birth and that maternal and perinatal exposures such as chemical and infectious agents are likely to be critical. Indeed, we have reported that exposure to indoor pesticides during pregnancy and the first year of life raises leukemia risk, but that later exposures do not. We have also examined aberrant gene methylation in different cytogenetic subgroups and have found striking differences between them, suggesting that epigenetic events are also important in the development of some forms of childhood leukemia. Further, at least two studies now show that the inactivating NAD(P)H:quinone acceptor oxidoreductase (NQO1) C609T polymorphism is positively associated with leukemias arising in the first 1-2 years of life and polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene have been associated with adult and childhood ALL. Thus, low folate intake and compounds that are detoxified by NQO1 may be important in elevating leukemia risk in children. Finally, we are exploring the use of proteomics to subclassify leukemia, because cytogenetic analysis is costly and time-consuming. Several proteins have been identified that may serve as useful biomarkers for rapidly identifying different forms of childhood leukemia

  13. Baseline Characteristics Predicting Very Good Outcome of Allogeneic Hematopoietic Cell Transplantation in Young Patients With High Cytogenetic Risk Chronic Lymphocytic Leukemia - A Retrospective Analysis From the Chronic Malignancies Working Party of the EBMT.

    Science.gov (United States)

    van Gelder, Michel; Ziagkos, Dimitris; de Wreede, Liesbeth; van Biezen, Anja; Dreger, Peter; Gramatzki, Martin; Stelljes, Matthias; Andersen, Niels Smedegaard; Schaap, Nicolaas; Vitek, Antonin; Beelen, Dietrich; Lindström, Vesa; Finke, Jürgen; Passweg, Jacob; Eder, Matthias; Machaczka, Maciej; Delgado, Julio; Krüger, William; Raida, Luděk; Socié, Gerard; Jindra, Pavel; Afanasyev, Boris; Wagner, Eva; Chalandon, Yves; Henseler, Anja; Schoenland, Stefan; Kröger, Nicolaus; Schetelig, Johannes

    2017-10-01

    Patients with genetically high-risk relapsed/refractory chronic lymphocytic leukemia have shorter median progression-free survival (PFS) with kinase- and BCL2-inhibitors (KI, BCL2i). Allogeneic hematopoietic stem cell transplantation (alloHCT) may result in sustained PFS, especially in younger patients because of its age-dependent non-relapse mortality (NRM) risk, but outcome data are lacking for this population. Risk factors for 2-year NRM and 8-year PFS were identified in patients < 50 years in an updated European Society for Blood and Marrow Transplantation registry cohort (n = 197; median follow-up, 90.4 months) by Cox regression modeling, and predicted probabilities of NRM and PFS of 2 reference patients with favorable or unfavorable characteristics were plotted. Predictors for poor 8-year PFS were no remission at the time of alloHCT (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.1-2.5) and partially human leukocyte antigen (HLA)-mismatched unrelated donor (HR, 2.8; 95% CI, 1.5-5.2). The latter variable also predicted a higher risk of 2-year NRM (HR, 4.0; 95% CI, 1.4-11.6) compared with HLA-matched sibling donors. Predicted 2-year NRM and 8-year PFS of a high cytogenetic risk (del(17p) and/or del(11q)) patient in remission with a matched related donor were 12% (95% CI, 3%-22%) and 54% (95% CI, 38%-69%), and for an unresponsive patient with a female partially HLA-matched unrelated donor 37% (95% CI, 12%-62%) and 38% (95% CI, 13%-63%). Low predicted NRM and high 8-year PFS in favorable transplant high cytogenetic risk patients compares favorably with outcomes with KI or BCL2i. Taking into account the amount of uncertainty for predicting survival after alloHCT and after sequential administration of KI and BCL2i, alloHCT remains a valid option for younger patients with high cytogenetic risk chronic lymphocytic leukemia with a well-HLA-matched donor. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Dose-response relationship of neutrons and γ rays to leukemia incidence among atomic bomb survivors in Hiroshima and Nagasaki by type of leukemia, 1950--1971

    International Nuclear Information System (INIS)

    Ishimaru, T.; Otake, M.; Ichimaru, M.

    1979-01-01

    The incidence of leukemia during 1950 to 1971 in a fixed mortality sample of atomic bomb survivors in Hiroshima and Nagasaki was analyzed as a function of neutron and γ kerma and marrow doses. Two dose-response models were tested for acute leukemia, chronic granulocytic leukemia, and all types of leukemia, respectively. Each model postulates that the leukemia incidence depends upon the sum of separate risks imposed by γ and neutron doses. In Model I the risk from both types of radiation is assumed to be directly proportional to the respective doses, while Model II assumes that whereas the risk from neutrons is directly proportional to the dose, the risk from γ rays is proportional to dose-squared. The analysis demonstrated that the dose-response of the two types of leukemia differed by type of radiation. The data suggested that the response of acute leukemia was best explained by Model II, while the response of chronic granulocytic leukemia depended almost linearly upon neutron dose alone, because the regression coefficients associated with γ radiation for both Models I and II were not significant. The relative biological effectiveness (RBE) of neutrons in relation to γ rays for incidence of acute leukemia was estimated to be approximately 30/(Dn)/sup 1/2/ [95% confidence limits; 17/(Dn)/sup 1/2/ approx. 54/(Dn)/sup 1/2/] for kerma and 32/(Dn)/sup 1/2/ [95% confidence limits; 18/(Dn)/sup 1/2/ approx. 58/(Dn)/sup 1/2/] for marrow dose (Dn = neutron dose). If acute and chronic granulocytic leukemias are considered together as all types of leukemia, Model II appears to fit the data slightly better than Model I, but neither model is statistically rejected by the data

  15. The contribution of benzene to smoking-induced leukemia.

    Science.gov (United States)

    Korte, J E; Hertz-Picciotto, I; Schulz, M R; Ball, L M; Duell, E J

    2000-04-01

    Cigarette smoking is associated with an increased risk of leukemia; benzene, an established leukemogen, is present in cigarette smoke. By combining epidemiologic data on the health effects of smoking with risk assessment techniques for low-dose extrapolation, we assessed the proportion of smoking-induced total leukemia and acute myeloid leukemia (AML) attributable to the benzene in cigarette smoke. We fit both linear and quadratic models to data from two benzene-exposed occupational cohorts to estimate the leukemogenic potency of benzene. Using multiple-decrement life tables, we calculated lifetime risks of total leukemia and AML deaths for never, light, and heavy smokers. We repeated these calculations, removing the effect of benzene in cigarettes based on the estimated potencies. From these life tables we determined smoking-attributable risks and benzene-attributable risks. The ratio of the latter to the former constitutes the proportion of smoking-induced cases attributable to benzene. Based on linear potency models, the benzene in cigarette smoke contributed from 8 to 48% of smoking-induced total leukemia deaths [95% upper confidence limit (UCL), 20-66%], and from 12 to 58% of smoking-induced AML deaths (95% UCL, 19-121%). The inclusion of a quadratic term yielded results that were comparable; however, potency models with only quadratic terms resulted in much lower attributable fractions--all models substantially overestimate low-dose risk, linear extrapolations from empirical data over a dose range of 10- to 100-fold resulted in plausible predictions.

  16. Neonatal Nurses Experience Unintended Consequences and Risks to Patient Safety With Electronic Health Records.

    Science.gov (United States)

    Dudding, Katherine M; Gephart, Sheila M; Carrington, Jane M

    2018-04-01

    In this article, we examine the unintended consequences of nurses' use of electronic health records. We define these as unforeseen events, change in workflow, or an unanticipated result of implementation and use of electronic health records. Unintended consequences experienced by nurses while using electronic health records have been well researched. However, few studies have focused on neonatal nurses, and it is unclear to what extent unintended consequences threaten patient safety. A new instrument called the Carrington-Gephart Unintended Consequences of Electronic Health Record Questionnaire has been validated, and secondary analysis using the tool explored the phenomena among neonatal nurses (N = 40). The purposes of this study were to describe unintended consequences of use of electronic health records for neonatal nurses and to explore relationships between the phenomena and characteristics of the nurse and the electronic health record. The most frequent unintended consequences of electronic health record use were due to interruptions, followed by a heavier workload due to the electronic health record, changes to the workflow, and altered communication patterns. Neonatal nurses used workarounds most often with motivation to better assist patients. Teamwork was moderately related to higher unintended consequences including patient safety risks (r = 0.427, P = .007), system design (r = 0.419, P = .009), and technology barriers (r = 0.431, P = .007). Communication about patients was reduced when patient safety risks were high (r = -0.437, P = .003). By determining the frequency with which neonatal nurses experience unintended consequences of electronic health record use, future research can be targeted to improve electronic health record design through customization, integration, and refinement to support patient safety and better outcomes.

  17. Traceability and Risk Analysis Strategies for Addressing Counterfeit Electronics in Supply Chains for Complex Systems.

    Science.gov (United States)

    DiMase, Daniel; Collier, Zachary A; Carlson, Jinae; Gray, Robin B; Linkov, Igor

    2016-10-01

    Within the microelectronics industry, there is a growing concern regarding the introduction of counterfeit electronic parts into the supply chain. Even though this problem is widespread, there have been limited attempts to implement risk-based approaches for testing and supply chain management. Supply chain risk management tends to focus on the highly visible disruptions of the supply chain instead of the covert entrance of counterfeits; thus counterfeit risk is difficult to mitigate. This article provides an overview of the complexities of the electronics supply chain, and highlights some gaps in risk assessment practices. In particular, this article calls for enhanced traceability capabilities to track and trace parts at risk through various stages of the supply chain. Placing the focus on risk-informed decision making through the following strategies is needed, including prioritization of high-risk parts, moving beyond certificates of conformance, incentivizing best supply chain management practices, adoption of industry standards, and design and management for supply chain resilience. © 2016 Society for Risk Analysis.

  18. The readmission risk flag: using the electronic health record to automatically identify patients at risk for 30-day readmission.

    Science.gov (United States)

    Baillie, Charles A; VanZandbergen, Christine; Tait, Gordon; Hanish, Asaf; Leas, Brian; French, Benjamin; Hanson, C William; Behta, Maryam; Umscheid, Craig A

    2013-12-01

    Identification of patients at high risk for readmission is a crucial step toward improving care and reducing readmissions. The adoption of electronic health records (EHR) may prove important to strategies designed to risk stratify patients and introduce targeted interventions. To develop and implement an automated prediction model integrated into our health system's EHR that identifies on admission patients at high risk for readmission within 30 days of discharge. Retrospective and prospective cohort. Healthcare system consisting of 3 hospitals. All adult patients admitted from August 2009 to September 2012. An automated readmission risk flag integrated into the EHR. Thirty-day all-cause and 7-day unplanned healthcare system readmissions. Using retrospective data, a single risk factor, ≥ 2 inpatient admissions in the past 12 months, was found to have the best balance of sensitivity (40%), positive predictive value (31%), and proportion of patients flagged (18%), with a C statistic of 0.62. Sensitivity (39%), positive predictive value (30%), proportion of patients flagged (18%), and C statistic (0.61) during the 12-month period after implementation of the risk flag were similar. There was no evidence for an effect of the intervention on 30-day all-cause and 7-day unplanned readmission rates in the 12-month period after implementation. An automated prediction model was effectively integrated into an existing EHR and identified patients on admission who were at risk for readmission within 30 days of discharge. © 2013 Society of Hospital Medicine.

  19. Coronary artery disease risk assessment from unstructured electronic health records using text mining.

    Science.gov (United States)

    Jonnagaddala, Jitendra; Liaw, Siaw-Teng; Ray, Pradeep; Kumar, Manish; Chang, Nai-Wen; Dai, Hong-Jie

    2015-12-01

    Coronary artery disease (CAD) often leads to myocardial infarction, which may be fatal. Risk factors can be used to predict CAD, which may subsequently lead to prevention or early intervention. Patient data such as co-morbidities, medication history, social history and family history are required to determine the risk factors for a disease. However, risk factor data are usually embedded in unstructured clinical narratives if the data is not collected specifically for risk assessment purposes. Clinical text mining can be used to extract data related to risk factors from unstructured clinical notes. This study presents methods to extract Framingham risk factors from unstructured electronic health records using clinical text mining and to calculate 10-year coronary artery disease risk scores in a cohort of diabetic patients. We developed a rule-based system to extract risk factors: age, gender, total cholesterol, HDL-C, blood pressure, diabetes history and smoking history. The results showed that the output from the text mining system was reliable, but there was a significant amount of missing data to calculate the Framingham risk score. A systematic approach for understanding missing data was followed by implementation of imputation strategies. An analysis of the 10-year Framingham risk scores for coronary artery disease in this cohort has shown that the majority of the diabetic patients are at moderate risk of CAD. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Congenital Leukemia in Down's syndrome

    International Nuclear Information System (INIS)

    Iqbal, W.; Khan, F.; Muzaffar, M.; Khan, U. A.; Rehman, M. U.; Khan, M. A.; Bari, A.

    2006-01-01

    Congenital Leukemia is a condition and often associated with fatal outcome/sup 1/. Most of the neonatal cases reported have acute non-lymphoblastic leukemia, in contrast to the predominance of acute lymphoblastic leukemia found in later childhood. congenital leukemia is occasionally associated with number of congenital anomalies and with chromosomal disorders such as Down's syndrome. Subtle cytogenetic abnormalities may occur more commonly in the affected infants and their parents, when studied with newer cytogenetic techniques/sup 2/. Inherent unstable hematopoieses resulting from chromosomal aberration in children with Downs's syndrome can present with transient myeloproliferative disorder, mimicking leukemia which undergoes spontaneous recovery/sup 3/. Only few cases of congenital leukemia with Downs syndrome, presented as congenital leukemia. (author)

  1. Prevalence and risk factors of electronic cigarette use among adolescents: Data from four Swedish municipalities

    Directory of Open Access Journals (Sweden)

    Geidne Susanna

    2016-07-01

    Full Text Available AIMS – To assess the prevalence rates and risk factors of electronic cigarette (e-cigarette use, with special focus on e-cigarettes containing nicotine, among grade 9 students (aged 15–16 years in four different municipalities in Sweden.

  2. Hazardous substances in electronics: the effects of European Union risk regulation on China

    NARCIS (Netherlands)

    Biedenkopf, K.

    2012-01-01

    This article argues that European Union (EU) risk regulation of hazardous substances in electrical and electronic equipment (EEE) was both a trigger and formative factor in the development of similar Chinese regulation. The attractiveness and global interdependence of the EU market in EEE impelled a

  3. Childhood acute lymphoblastic leukemia: from genome to patient

    International Nuclear Information System (INIS)

    Kolenova, A.

    2016-01-01

    Acute lymphoblastic leukemia is the most common malignant disease in childhood. During recent decades prognosis for children with acute leukemia has greatly improved, including the patients treated in the Slovak Republic. The prognosis for these patients has improved as a result of the systematic and well-organized international research efforts and clinical trials. The advent of new genomic technologies has provided new insights into leukemogenesis, identified many novel subtypes of leukemia, and triggered development of new therapeutic formulations. The success of treatment depends on stratifying patients into risk group and incorporating novel treatment strategies.The Slovak pediatric leukemia group is actively incorporated into these international clinical trials and the outcome for our patients is comparable to the results published in Western Europe. (author)

  4. Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Pui, Ching-Hon; Yang, Jun J; Hunger, Stephen P

    2015-01-01

    PURPOSE: To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. METHODS: A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article...

  5. Mouse models in leukemia

    NARCIS (Netherlands)

    Voncken, J.W.

    1995-01-01

    Human Philadelphia-positive leukemia results from a balanced chromosomal translocation, which fuses the BCR gene on chromosome 22 to the ABL proto-oncogene on chromosome 9. The understanding of Ph-positive leukemogenesis has advanced enormously over

  6. Leukemia & Lymphoma Society

    Science.gov (United States)

    ... be the exclusive property of The Leukemia & Lymphoma Society which in its sole discretion may use this material as it sees fit. I agree to the terms of the Standard Photography Release.* Submit * This field is required * Please fix the validation error messages in the Form Your story was ...

  7. Utilizing Dental Electronic Health Records Data to Predict Risk for Periodontal Disease.

    Science.gov (United States)

    Thyvalikakath, Thankam P; Padman, Rema; Vyawahare, Karnali; Darade, Pratiksha; Paranjape, Rhucha

    2015-01-01

    Periodontal disease is a major cause for tooth loss and adversely affects individuals' oral health and quality of life. Research shows its potential association with systemic diseases like diabetes and cardiovascular disease, and social habits such as smoking. This study explores mining potential risk factors from dental electronic health records to predict and display patients' contextualized risk for periodontal disease. We retrieved relevant risk factors from structured and unstructured data on 2,370 patients who underwent comprehensive oral examinations at the Indiana University School of Dentistry, Indianapolis, IN, USA. Predicting overall risk and displaying relationships between risk factors and their influence on the patient's oral and general health can be a powerful educational and disease management tool for patients and clinicians at the point of care.

  8. Identification of Patient Safety Risks Associated with Electronic Health Records: A Software Quality Perspective.

    Science.gov (United States)

    Virginio, Luiz A; Ricarte, Ivan Luiz Marques

    2015-01-01

    Although Electronic Health Records (EHR) can offer benefits to the health care process, there is a growing body of evidence that these systems can also incur risks to patient safety when developed or used improperly. This work is a literature review to identify these risks from a software quality perspective. Therefore, the risks were classified based on the ISO/IEC 25010 software quality model. The risks identified were related mainly to the characteristics of "functional suitability" (i.e., software bugs) and "usability" (i.e., interface prone to user error). This work elucidates the fact that EHR quality problems can adversely affect patient safety, resulting in errors such as incorrect patient identification, incorrect calculation of medication dosages, and lack of access to patient data. Therefore, the risks presented here provide the basis for developers and EHR regulating bodies to pay attention to the quality aspects of these systems that can result in patient harm.

  9. Investigating the role of electronic insurance on decreasing exporting charges risks

    Directory of Open Access Journals (Sweden)

    Farideh MosallaiZade

    2014-07-01

    Full Text Available Nowadays, the electronic insurance (EI is one the electronic services, which is used in most countries, and that is one effective factor in developing the exporting products and services. On the other hand, the incurrence industry and very especially EI represent their importance both domestically and internationally. One of the ways for transferring the exporting risks is to transfer the risks to the insurer. This paper examines the characteristics of EI and the effects of decreasing the exporting risk charges. The proposed study designs a questionnaire in the form of Likert scale, the validity of the questionnaire is validated by some the experts' viewpoints and the Cronbach' alpha is measure as 0.794. The results of applying Freedman test have disclosed that facilitating export activities was the most important factor followed by access to target export market information.

  10. Birth weight and other perinatal characteristics and childhood leukemia in California.

    Science.gov (United States)

    Oksuzyan, S; Crespi, C M; Cockburn, M; Mezei, G; Kheifets, L

    2012-12-01

    We conducted a large registry-based study in California to investigate the association of perinatal factors and childhood leukemia with analysis of two major subtypes, acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML). We linked California cancer and birth registries to obtain information on 5788 cases and 5788 controls matched on age and sex (1:1). We examined the association of birth weight, gestational age, birth and pregnancy order, parental ages, and specific conditions during pregnancy and risk of total leukemia, ALL and AML using conditional logistic regression, with adjustment for potential confounders. The odds ratio (OR) per 1000 g increase in birth weight was 1.11 for both total leukemia and ALL. The OR were highest for babies weighing ≥ 4500 g with reference birth weight and LGA were associated with increased risk and SGA with decreased risk of total childhood leukemia and ALL, being first-born was associated with decreased risk of AML, and advanced paternal age was associated with increased risk of ALL. These findings suggest that associations of childhood leukemia and perinatal factors depend highly on subtype of leukemia. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. DIAGNOSIS AND SUBCLASSIFICATION OF ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Sabina Chiaretti

    2014-10-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a disseminated malignancy of B- or T-lymphoblasts which imposes a rapid and accurate diagnostic process to support an optimal risk-oriented therapy and thus increase the curability rate. The need for a precise diagnostic algorithm is underlined by the awareness that both ALL therapy and related success rates may vary greatly in function of ALL subset, from standard chemotherapy in patients with standard-risk ALL, to allotransplantation (SCT and targeted therapy in high-risk patients and cases expressing suitable biological targets, respectively. This review offers a glimpse on how best identify ALL and the most relevant ALL subsets.

  12. Childhood leukemia around nuclear facilities

    International Nuclear Information System (INIS)

    Hatch, M.

    1992-01-01

    Epidemiologic studies on health effects of living near nuclear facilities have been rare and, indeed, radiobiological models would not predict any detectable increase in cancer risk to the general public from very low levels of radioactivity emitted by nuclear installations. Thus recent evidence suggesting an excess of childhood leukemias in the vicinity of certain nuclear sites in the United Kingdom has generated considerable controversy. To help resolve the uncertainty and enhance interpretability of results, future epidemiologic studies will need to be designed with great care (and within realistic cost limits). This commentary suggests three areas for methodologic consideration: 1. definition and modelling of radiation exposure; 2. selection of cancer sites and sensitive subgroups, and 3. use of incidence of mortality data. Specific suggestions for further epidemiologic research are offered as well. (author). 8 refs

  13. Low Body Mass Index Is Associated with Increased Risk of Acute GVHD after Umbilical Cord Blood Transplantation in Children and Young Adults with Acute Leukemia: A Study on Behalf of Eurocord and the EBMT Pediatric Disease Working Party.

    Science.gov (United States)

    Paviglianiti, Annalisa; Dalle, Jean Hugues; Ayas, Mouhab; Boelens, Jan Jaap; Volt, Fernanda; Iori, Anna Paola; de Souza, Mair Pedro; Diaz, Miguel Angel; Michel, Gerard; Locatelli, Franco; Jubert, Charlotte; Yakoub-Agha, Ibrahim; Bittencourt, Henrique; Bertrand, Yves; Kenzey, Chantal; Tozatto Maio, Karina; Hayashi, Hiromi; Rocha, Vanderson; Bader, Peter; Gluckman, Eliane; Ruggeri, Annalisa

    2018-04-01

    Body mass index (BMI) may influence outcomes after allogeneic hematopoietic stem cell transplantation (HSCT). However, the impact of BMI on survival in children undergoing HSCT is not well defined, with conflicting results being reported on this issue. We analyzed 855 patients age 2 to 20 years with diagnosis of acute leukemia who underwent umbilical cord blood transplantation (UCBT) from 1990 to 2015. Patients were classified according to BMI as normal (fifth to 85th percentile), underweight (less than fifth percentile), overweight (85th to 95th percentile), and obese (>95th percentile) using growth charts for age and sex. All patients received single-unit UCBT after a myeloablative conditioning regimen. Diagnosis was acute lymphoblastic leukemia in 68% of the patients. Sixty-one percent of patients (n = 523) were in the normal BMI category, 11% (n = 96) were underweight, 16% (n = 137) overweight, and 12% (n = 99) obese. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was 35% (32% to 38%). According to pretransplantation BMI, aGVHD was 46% (33% to 59%) for underweight, 34% (31% to 42%) for normal, 36% (18% to 38%) for overweight, and 27% (15% to 37%) for obese (P = .04). In multivariate analysis, a BMI less than the fifth percentile was associated with higher incidence of acute grade II to IV GVHD compared with normal-BMI patients (hazard ratio,  1.61; 95% confidence interval, 1.15 to 2.26; P = .006). Our results show that being underweight at the time of transplantation is associated with an increased risk of aGVHD, highlighting the importance of nutritional status before UCBT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  14. Donor-Cell Origin High-Risk Myelodysplastic Syndrome Synchronous with an Intracranial Meningioma-Like Tumor, 8 Years after Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    G. Brás

    2017-01-01

    Full Text Available Secondary neoplasias are well known consequences of radiotherapy or chemotherapy for a primary cancer. In this report, we describe two rare secondary neoplasias occurring in the same patient: a meningioma-like intracranial tumor and high-risk myelodysplastic syndrome (MDS of donor-cells origin, both diagnosed simultaneously, 8 years after an allogeneic hematopoietic stem cell transplantation (allo-HSCT for chronic lymphocytic leukemia (CLL. Due to an engraftment failure during the first allo-HSCT of a matched related donor for CLL treatment, the salvage treatment was a second allo-HSCT. At the moment of meningioma-like tumor diagnosis, the patient was pancytopenic due to high-risk MDS, so it was decided to postpone a surgical intervention until hematological improvement. For the high-risk MDS of donor-cells origin the chosen treatment was induction with intensive chemotherapy. Due to refractory disease, the patient was treated with 5-azacitidine and donor-lymphocytes infusion with no response and, finally, a third allo-HSCT of a matched unrelated donor was performed. The patient died 6 months after the third allo-HSCT, in cytogenetic remission but without hematological recovery, due to an intracranial hemorrhage with origin in the meningioma-like tumor.

  15. Association of body mass index and survival in pediatric leukemia: a meta-analysis.

    Science.gov (United States)

    Orgel, Etan; Genkinger, Jeanine M; Aggarwal, Divya; Sung, Lillian; Nieder, Michael; Ladas, Elena J

    2016-03-01

    Obesity is a worldwide epidemic in children and adolescents. Adult cohort studies have reported an association between higher body mass index (BMI) and increased leukemia-related mortality; whether a similar effect exists in childhood leukemia remains controversial. We conducted a meta-analysis to determine whether a higher BMI at diagnosis of pediatric acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) is associated with worse event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR). We searched 4 electronic databases from inception through March 2015 without language restriction and included studies in pediatric ALL or AML (0-21 y of age) reporting BMI as a predictor of survival or relapse. Higher BMI, defined as obese (≥95%) or overweight/obese (≥85%), was compared with lower BMI [nonoverweight/obese (children with a higher BMI (RR: 1.35; 95% CI: 1.20, 1.51) than in those at a lower BMI. A higher BMI was associated with significantly increased mortality (RR: 1.31; 95% CI: 1.09, 1.58) and a statistically nonsignificant trend toward greater risk of relapse (RR: 1.17; 95% CI: 0.99, 1.38) compared with a lower BMI. In AML, a higher BMI was significantly associated with poorer EFS and OS (RR: 1.36; 95% CI: 1.16, 1.60 and RR: 1.56; 95% CI: 1.32, 1.86, respectively) than was a lower BMI. Higher BMI at diagnosis is associated with poorer survival in children with pediatric ALL or AML. © 2016 American Society for Nutrition.

  16. The human polynucleotide kinase/phosphatase (hPNKP) inhibitor A12B4C3 radiosensitizes human myeloid leukemia cells to Auger electron-emitting anti-CD123 111In-NLS-7G3 radioimmunoconjugates

    International Nuclear Information System (INIS)

    Zereshkian, Arman; Leyton, Jeffrey V.; Cai, Zhongli; Bergstrom, Dane; Weinfeld, Michael; Reilly, Raymond M.

    2014-01-01

    Introduction: Leukemia stem cells (LSCs) are believed to be responsible for initiating and propagating acute myeloid leukemia (AML) and for causing relapse after treatment. Radioimmunotherapy (RIT) targeting these cells may improve the treatment of AML, but is limited by the low density of target epitopes. Our objective was to study a human polynucleotide kinase/phosphatase (hPNKP) inhibitor that interferes with DNA repair as a radiosensitizer for the Auger electron RIT agent, 111 In-NLS-7G3, which recognizes the CD123 + /CD131 - phenotype uniquely displayed by LSCs. Methods: The surviving fraction (SF) of CD123 + /CD131 - AML-5 cells exposed to 111 In-NLS-7G3 (33–266 nmols/L; 0.74 MBq/μg) or to γ-radiation (0.25-5 Gy) was determined by clonogenic assays. The effect of A12B4C3 (25 μmols/L) combined with 111 In-NLS-7G3 (16–66 nmols/L) or with γ-radiation (0.25–2 Gy) on the SF of AML-5 cells was assessed. The density of DNA double-strand breaks (DSBs) in the nucleus was measured using the γ-H2AX assay. Cellular dosimetry was estimated based on the subcellular distribution of 111 In-NLS-7G3 measured by cell fractionation. Results: Binding of 111 In-NLS-7G3 to AML-5 cells was reduced by 2.2-fold in the presence of an excess (1 μM) of unlabeled NLS-7G3, demonstrating specific binding to the CD123 + /CD131 - epitope. 111 In-NLS-7G3 reduced the SF of AML-5 cells from 86.1 ± 11.0% at 33 nmols/L to 10.5 ± 3.6% at 266 nmols/L. Unlabeled NLS-7G3 had no significant effect on the SF. Treatment of AML-5 cells with γ-radiation reduced the SF from 98.9 ± 14.9% at 0.25 Gy to 0.03 ± 0.1% at 5 Gy. A12B4C3 combined with 111 In-NLS-7G3 (16–66 nmols/L) enhanced the cytotoxicity up to 1.7-fold compared to treatment with radioimmunoconjugates alone and was associated with a 1.6-fold increase in DNA DSBs in the nucleus. A12B4C3 enhanced the cytotoxicity of γ-radiation (0.25–0.5 Gy) on AML-5 cells by up to 1.5-fold, and DNA DSBs were increased by 1.7-fold. Exposure to

  17. Trends in adult leukemia incidence and survival in Denmark, 1943-2003

    DEFF Research Database (Denmark)

    Thygesen, Lau Caspar; Nielsen, Ove Juul; Johansen, Christoffer

    2009-01-01

    The etiology of leukemia is largely unknown. Ecological data indicating trends in incidence and survival can provide information about changes in risk factors, can reflect underlying changes in diagnostic classification, and can measure therapeutic advances. From the records of the Danish Cancer...... Registry with registration starting from 1943, we calculated age-specific, period-specific, and age-standardized (world standard) incidence rates of chronic lymphoid leukemia (CLL), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML), and acute myeloid leukemia (AML) for persons above the age...... of 18. Kaplan-Meier survival curves and median survival times were calculated. Between 1943 and 2003, there were 26,036 cases of leukemia reported. The age-specific incidence rates of CLL, CML, and AML were higher for older men and women, while the incidence rates of ALL by age were more homogeneous...

  18. Acute Lymphoblastic Leukemia (ALL) (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Acute Lymphoblastic Leukemia (ALL) KidsHealth / For Parents / Acute Lymphoblastic Leukemia (ALL) What's in this article? About Leukemia Causes ...

  19. Ultra-sensitive detection of leukemia by graphene

    Science.gov (United States)

    Akhavan, Omid; Ghaderi, Elham; Hashemi, Ehsan; Rahighi, Reza

    2014-11-01

    Graphene oxide nanoplatelets (GONPs) with extremely sharp edges (lateral dimensions ~20-200 nm and thicknesses leukemia cells. The blood serums containing the extracted guanine were used in differential pulse voltammetry (DPV) with reduced graphene oxide nanowall (rGONW) electrodes to develop fast and ultra-sensitive electrochemical detection of leukemia cells at leukemia fractions (LFs) of ~10-11 (as the lower detection limit). The stability of the DPV signals obtained by oxidation of the extracted guanine on the rGONWs was studied after 20 cycles. Without the guanine extraction, the DPV peaks relating to guanine oxidation of normal and abnormal cells overlapped at LFs diagnosis.Graphene oxide nanoplatelets (GONPs) with extremely sharp edges (lateral dimensions ~20-200 nm and thicknesses leukemia cells. The blood serums containing the extracted guanine were used in differential pulse voltammetry (DPV) with reduced graphene oxide nanowall (rGONW) electrodes to develop fast and ultra-sensitive electrochemical detection of leukemia cells at leukemia fractions (LFs) of ~10-11 (as the lower detection limit). The stability of the DPV signals obtained by oxidation of the extracted guanine on the rGONWs was studied after 20 cycles. Without the guanine extraction, the DPV peaks relating to guanine oxidation of normal and abnormal cells overlapped at LFs diagnosis. Electronic supplementary information (ESI) available. See DOI: 10.1039/C4NR04589K

  20. A probabilistic topic model for clinical risk stratification from electronic health records.

    Science.gov (United States)

    Huang, Zhengxing; Dong, Wei; Duan, Huilong

    2015-12-01

    Risk stratification aims to provide physicians with the accurate assessment of a patient's clinical risk such that an individualized prevention or management strategy can be developed and delivered. Existing risk stratification techniques mainly focus on predicting the overall risk of an individual patient in a supervised manner, and, at the cohort level, often offer little insight beyond a flat score-based segmentation from the labeled clinical dataset. To this end, in this paper, we propose a new approach for risk stratification by exploring a large volume of electronic health records (EHRs) in an unsupervised fashion. Along this line, this paper proposes a novel probabilistic topic modeling framework called probabilistic risk stratification model (PRSM) based on Latent Dirichlet Allocation (LDA). The proposed PRSM recognizes a patient clinical state as a probabilistic combination of latent sub-profiles, and generates sub-profile-specific risk tiers of patients from their EHRs in a fully unsupervised fashion. The achieved stratification results can be easily recognized as high-, medium- and low-risk, respectively. In addition, we present an extension of PRSM, called weakly supervised PRSM (WS-PRSM) by incorporating minimum prior information into the model, in order to improve the risk stratification accuracy, and to make our models highly portable to risk stratification tasks of various diseases. We verify the effectiveness of the proposed approach on a clinical dataset containing 3463 coronary heart disease (CHD) patient instances. Both PRSM and WS-PRSM were compared with two established supervised risk stratification algorithms, i.e., logistic regression and support vector machine, and showed the effectiveness of our models in risk stratification of CHD in terms of the Area Under the receiver operating characteristic Curve (AUC) analysis. As well, in comparison with PRSM, WS-PRSM has over 2% performance gain, on the experimental dataset, demonstrating that

  1. Use and Customization of Risk Scores for Predicting Cardiovascular Events Using Electronic Health Record Data.

    Science.gov (United States)

    Wolfson, Julian; Vock, David M; Bandyopadhyay, Sunayan; Kottke, Thomas; Vazquez-Benitez, Gabriela; Johnson, Paul; Adomavicius, Gediminas; O'Connor, Patrick J

    2017-04-24

    Clinicians who are using the Framingham Risk Score (FRS) or the American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE) to estimate risk for their patients based on electronic health data (EHD) face 4 questions. (1) Do published risk scores applied to EHD yield accurate estimates of cardiovascular risk? (2) Are FRS risk estimates, which are based on data that are up to 45 years old, valid for a contemporary patient population seeking routine care? (3) Do the PCE make the FRS obsolete? (4) Does refitting the risk score using EHD improve the accuracy of risk estimates? Data were extracted from the EHD of 84 116 adults aged 40 to 79 years who received care at a large healthcare delivery and insurance organization between 2001 and 2011. We assessed calibration and discrimination for 4 risk scores: published versions of FRS and PCE and versions obtained by refitting models using a subset of the available EHD. The published FRS was well calibrated (calibration statistic K=9.1, miscalibration ranging from 0% to 17% across risk groups), but the PCE displayed modest evidence of miscalibration (calibration statistic K=43.7, miscalibration from 9% to 31%). Discrimination was similar in both models (C-index=0.740 for FRS, 0.747 for PCE). Refitting the published models using EHD did not substantially improve calibration or discrimination. We conclude that published cardiovascular risk models can be successfully applied to EHD to estimate cardiovascular risk; the FRS remains valid and is not obsolete; and model refitting does not meaningfully improve the accuracy of risk estimates. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  2. Leukemia after radiotherapy for first primary cancers of various anatomic sites

    International Nuclear Information System (INIS)

    Boivin, J.F.; Hutchison, G.B.; Evans, F.B.; Abou-Daoud, K.T.; Junod, B.

    1986-01-01

    The authors conducted a case-control study designed to evaluate the association between radiotherapy for a first primary cancer and subsequent leukemia risk. Study subjects were selected from four tumor registries (California, Connecticut, Kansas, and Massachusetts). Cases were subjects with two primary concers; the second cancer was a leukemia diagnosed one year or more after the diagnosis of the first primary cancer. Control subjects were patients with single cancers. Two control subjects were chosen for each case matched for tumor registry, site of the first primary cancer, date of diagnosis of the first primary cancer, age, sex, and duration of survival after the first primary cancer. Separate analyses were carried out for chronic lymphatic leukemia (166 cases) and all other leukemias (232 cases). The relative risk of chronic lymphatic leukemia after radiotherapy was 0.7 and did not differ significantly from unity. For all other leukemias, relative risks were 1.6 after radiotherapy for first primary cancers of all sites, 2.4 after radiotherapy to trunk sites, 2.2 after radiotherapy for breast cancer, and 10.3 after radiotherapy for cancer of the corpus uteri. These relative risks for leukemias other than chronic lymphatic leukemia all differed significantly from unity

  3. Delayed Neurotoxicity Associated with Therapy for Children with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Cole, Peter D.; Kamen, Barton A.

    2006-01-01

    Most children diagnosed today with acute lymphoblastic leukemia (ALL) will be cured. However, treatment entails risk of neurotoxicity, causing deficits in neurocognitive function that can persist in the years after treatment is completed. Many of the components of leukemia therapy can contribute to adverse neurologic sequelae, including…

  4. Risk mitigation strategy for the ITER electron cyclotron upper port launcher

    International Nuclear Information System (INIS)

    Goede, A.P.H.; Bongers, W.A.; Elzendoorn, B.S.Q.; Graswinckel, M.F.; Baar, M.R. de

    2010-01-01

    A basic requirement for ITER equipment to meet is a high level of reliability, because ITER operation time is precious and radioactive operation leaves limited scope for repair. In order to reduce the risk of failure during ITER operation an effective risk mitigation strategy is necessary. This paper presents such strategy for the ITER electron cyclotron upper port launcher (ECUPL). A preliminary ECUPL risk analysis identifies possible failure modes. A probabilistic risk assessment quantifies the risk of failure using a 4 x 4 impact-likelihood matrix. Impact is quantified through technical, cost and schedule elements. Likelihood depends on the risk mitigation strategy adopted. A cost benefit analysis determines the most cost effective risk mitigation strategy. An essential element in risk mitigation is the testing of equipment prior to installation on the ITER machine. This paper argues the need for low- and highpower millimetre wave tests carried out on the fully assembled ECUPL. It presents a conceptual design for a dedicated on-site test bed that can handle 2 of 8 microwave beams at 2 MW long pulse operation.

  5. Leukemia and radium groundwater contamination

    International Nuclear Information System (INIS)

    Tracy, B.L.; Letourneau, E.G.

    1986-01-01

    In the August 2, 1985, issue of JAMMA, Lyman et al claim to have shown an association between leukemia incidence in Florida and radium in groundwater supplies. Although cautious in their conclusions, the authors imply that this excess in leukemia was in fact caused by radiation. The authors believe they have not presented a convincing argument for causation. The radiation doses at these levels of exposure could account for only a tiny fraction of the leukemia excess

  6. Predicting Risk of Suicide Attempt Using History of Physical Illnesses From Electronic Medical Records

    Science.gov (United States)

    Luo, Wei; Tran, Truyen; Berk, Michael; Venkatesh, Svetha

    2016-01-01

    Background Although physical illnesses, routinely documented in electronic medical records (EMR), have been found to be a contributing factor to suicides, no automated systems use this information to predict suicide risk. Objective The aim of this study is to quantify the impact of physical illnesses on suicide risk, and develop a predictive model that captures this relationship using EMR data. Methods We used history of physical illnesses (except chapter V: Mental and behavioral disorders) from EMR data over different time-periods to build a lookup table that contains the probability of suicide risk for each chapter of the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes. The lookup table was then used to predict the probability of suicide risk for any new assessment. Based on the different lengths of history of physical illnesses, we developed six different models to predict suicide risk. We tested the performance of developed models to predict 90-day risk using historical data over differing time-periods ranging from 3 to 48 months. A total of 16,858 assessments from 7399 mental health patients with at least one risk assessment was used for the validation of the developed model. The performance was measured using area under the receiver operating characteristic curve (AUC). Results The best predictive results were derived (AUC=0.71) using combined data across all time-periods, which significantly outperformed the clinical baseline derived from routine risk assessment (AUC=0.56). The proposed approach thus shows potential to be incorporated in the broader risk assessment processes used by clinicians. Conclusions This study provides a novel approach to exploit the history of physical illnesses extracted from EMR (ICD-10 codes without chapter V-mental and behavioral disorders) to predict suicide risk, and this model outperforms existing clinical assessments of suicide risk. PMID:27400764

  7. Minimal Residual Disease in Acute Myeloid Leukemia

    Science.gov (United States)

    Hourigan, Christopher S.; Karp, Judith E.

    2014-01-01

    Technological advances in the laboratory have lead to substantial improvements in clinical decision-making by the use of pre-treatment prognostic risk stratification factors in acute myeloid leukemia (AML). Unfortunately similar progress has not been made in treatment response criteria, with the definition of “complete remission” in AML largely unchanged for over half a century. Several recent clinical trials have demonstrated that higher sensitivity measurements of residual disease burden during or after treatment can be performed, that results are predictive for clinical outcome and can be used to improve outcomes by guiding additional therapeutic intervention to patients in clinical complete remission but at increased relapse risk. We review here these recent trials, the characteristics and challenges of the modalities currently used to detect minimal residual disease (MRD), and outline opportunities to both refine detection and better clinically utilize MRD measurements. MRD measurement is already the standard of care in other myeloid malignancies such as chronic myelogenous leukemia (CML) and acute promyelocytic leukemia (APL). It is our belief that response criteria for non-APL AML should be updated to include assessment for molecular complete remission (mCR) and that recommendations for post-consolidation surveillance should include regular monitoring for molecular relapse as a standard of care. PMID:23799371

  8. Validation of a Delirium Risk Assessment Using Electronic Medical Record Information.

    Science.gov (United States)

    Rudolph, James L; Doherty, Kelly; Kelly, Brittany; Driver, Jane A; Archambault, Elizabeth

    2016-03-01

    Identifying patients at risk for delirium allows prompt application of prevention, diagnostic, and treatment strategies; but is rarely done. Once delirium develops, patients are more likely to need posthospitalization skilled care. This study developed an a priori electronic prediction rule using independent risk factors identified in a National Center of Clinical Excellence meta-analysis and validated the ability to predict delirium in 2 cohorts. Retrospective analysis followed by prospective validation. Tertiary VA Hospital in New England. A total of 27,625 medical records of hospitalized patients and 246 prospectively enrolled patients admitted to the hospital. The electronic delirium risk prediction rule was created using data obtained from the patient electronic medical record (EMR). The primary outcome, delirium, was identified 2 ways: (1) from the EMR (retrospective cohort) and (2) clinical assessment on enrollment and daily thereafter (prospective participants). We assessed discrimination of the delirium prediction rule with the C-statistic. Secondary outcomes were length of stay and discharge to rehabilitation. Retrospectively, delirium was identified in 8% of medical records (n = 2343); prospectively, delirium during hospitalization was present in 26% of participants (n = 64). In the retrospective cohort, medical record delirium was identified in 2%, 3%, 11%, and 38% of the low, intermediate, high, and very high-risk groups, respectively (C-statistic = 0.81; 95% confidence interval 0.80-0.82). Prospectively, the electronic prediction rule identified delirium in 15%, 18%, 31%, and 55% of these groups (C-statistic = 0.69; 95% confidence interval 0.61-0.77). Compared with low-risk patients, those at high- or very high delirium risk had increased length of stay (5.7 ± 5.6 vs 3.7 ± 2.7 days; P = .001) and higher rates of discharge to rehabilitation (8.9% vs 20.8%; P = .02). Automatic calculation of delirium risk using an EMR algorithm identifies patients at

  9. Global Characteristics of Childhood Acute Promyelocytic Leukemia

    Science.gov (United States)

    Zhang, L; Samad, A; Pombo-de-Oliveira, MS; Scelo, G; Smith, MT; Feusner, J; Wiemels, JL; Metayer, C

    2014-01-01

    Acute promyelocytic leukemia (APL) comprises approximately 5–10% of childhood acute myeloid leukemia (AML) cases in the US. While variation in this percentage among other populations was noted previously, global patterns of childhood APL have not been thoroughly characterized. In this comprehensive review of childhood APL, we examined its geographic pattern and the potential contribution of environmental factors to observed variation. In 142 studies (spanning >60 countries) identified, variation was apparent—de novo APL represented from 2% (Switzerland) to >50% (Nicaragua) of childhood AML in different geographic regions. Because a limited number of previous studies addressed specific environmental exposures that potentially underlie childhood APL development, we gathered 28 childhood cases of therapy-related APL, which exemplified associations between prior exposures to chemotherapeutic drugs/radiation and APL diagnosis. Future population-based studies examining childhood APL patterns and the potential association with specific environmental exposures and other risk factors are needed. PMID:25445717

  10. Paradoxical effects of Auger electron-emitting 111In-DTPA-NLS-CSL360 radioimmunoconjugates on hCD45+ cells in the bone marrow and spleen of leukemia-engrafted NOD/SCID or NRG mice

    International Nuclear Information System (INIS)

    Bergstrom, Dane; Leyton, Jeffrey V.; Zereshkian, Arman; Chan, Conrad; Cai, Zhongli; Reilly, Raymond M.

    2016-01-01

    Introduction: 111 In-DTPA-NLS-CSL360 radioimmunoconjugates (RIC) recognize the overexpression of the interleukin-3 receptor α-subchain (CD123) relative to the β-subchain (CD131) on leukemia stem cells (LSC). Our aim was to study Auger electron radioimmunotherapy (RIT) of acute myeloid leukemia (AML) with 111 In-DTPA-NLS-CSL360 in non-obese diabetic severe combined immunodeficiency (NOD/SCID) mice or NOD-Rag1 null IL2rγ null (NRG) mice engrafted with CD123 + human AML-5 cells. Methods: The toxicity of three doses of 111 In-DTPA-NLS-CSL360 (3.3–4.8 MBq; 11–15 μg each) injected i.v. every two weeks was studied in non-engrafted NOD/SCID or NRG mice pre-treated with 200 cGy of γ-radiation required for AML engraftment. Engraftment efficiency of (1–5) × 10 6 cells AML-5 cells inoculated i.v. into NOD/SCID or NRG mice was assessed by flow cytometric analysis for human CD45 + (hCD45 + ) cells in the bone marrow (BM) and spleen. AML-5 engrafted mice were treated with two or three doses (3.7 MBq; 10 μg each) every two weeks of 111 In-DTPA-NLS-CSL360, non-specific 111 In-DTPA-NLS-hIgG, unlabeled CSL360 (10 μg) or normal saline. The percentage of hCD45 + cells in the BM and spleen were measured at one week after completion of treatment. Results: 111 In-DTPA-NLS-CSL360 in combination with 200 cGy of γ-radiation caused an initial transient decrease in body weight in NOD/SCID but not in NRG mice. There were no hematological, liver or kidney toxicities. The spleen exhibited 13-fold lower engraftment efficiency than the BM in NOD/SCID mice inoculated with 1 × 10 6 cells but both organs were highly (>85%) engrafted in NRG mice. Unexpectedly, 111 In-DTPA-NLS-CSL360 or non-specific 111 In-DTPA-NLS-hIgG caused a paradoxical 1.5-fold increase (P < 0.0001) in the proportion of hCD45 + cells in the BM of NOD/SCID mice compared to normal saline treated mice. 111 In-DTPA-NLS-CSL360 reduced hCD45 + cells in the spleen by 3.0-fold compared to 111 In-DTPA-NLS-hIgG (P = 0

  11. Incidence of leukemia among atomic bomb survivors in relation to neutron and gamma dose, Hiroshima and Nagasaki, 1950-71

    International Nuclear Information System (INIS)

    Ishimaru, Toranosuke; Otake, Masanori; Ichimaru, Michito.

    1978-03-01

    The incidence of leukemia during 1950-71 in the fixed mortality sample of atomic bomb survivors in Hiroshima and Nagasaki has been analyzed as a function of individual gamma and neutron kerma and marrow dose. Two dose response models were tested for each of acute leukemia, chronic granulocytic leukemia, and all types of leukemia, respectively. Each model postulates that leukemia incidence depends upon the sum of the separate risks imposed by the gamma ray and neutron doses; in Model I both are assumed to be directly proportional to the respective doses, while Model II assumes that while the risk from neutrons is directly proportional to the dose, the risk from gamma rays is proportional to dose-squared. Weighted regression analyses were performed for each model. When the two models were fitted to the data for all types of leukemia, the estimated regression coefficients corresponding to the neutron and gamma ray doses both differed significantly from zero, for each model. However, when analysis was restricted to acute leukemia, both the neutron and gamma ray coefficients were significant only for Model II, and with respect to chronic granulocytic leukemia, only the coefficient of the neutron dose was significant, using either Model I or Model II. It appeared that the responses of the two leukemia types differed by type of radiation. If the chronic granulocytic and acute leukemias are considered together, the Model II appears to fit the data slightly better than Model I, but neither models is rejected by the data. (author)

  12. Leukemia incidence among individuals exposed in utero, children of atomic bomb survivors, and their controls; Hiroshima and Nagasaki, 1945-79

    International Nuclear Information System (INIS)

    Ishimaru, Toranosuke; Ichimaru, Michito; Mikami, Motoko.

    1982-03-01

    The incidence of leukemia has been analyzed in relation to the fetal dose of individuals exposed in utero, and the parental gonadal dose of individuals born to atomic bomb survivors and controls in the two fixed RERF cohorts. Among 3,636 in utero exposed children and controls, 3 leukemia cases have been identified through 1979. No excess risk of leukemia for in utero exposed children is apparent. For children born to exposed parents and controls, 36 leukemia cases have been identified in the years 1946-79 among 50,689 study subjects where the parental gonadal dose is available. Again, no excess risk of leukemia exists. (author)

  13. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

    2016-01-01

    Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic...... leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were...

  14. Childhood leukemia and fallout from the Nevada nuclear tests

    International Nuclear Information System (INIS)

    Land, C.E.; McKay, F.W.; Machado, S.G.

    1984-01-01

    Cancer mortality data from the National Center for Health Statistics, covering the period 1950 through 1978, were used to test a reported association between childhood leukemia and exposure to radioactive fallout from nuclear weapons tests in Nevada between 1951 and 1958. No pattern of temporal and geographic variation in risk supportive of the reported association was found. Comparison of these results with those presented in support of an association of risk with fallout suggests that the purported association merely reflects an anomalously low leukemia rate in southern Utah during the period 1944 to 1949. 14 references, 4 figures, 7 tables

  15. SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

    Science.gov (United States)

    2013-01-10

    Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  16. The effect of introducing increased-reliability-risk electronic components into 3rd generation telecommunications systems

    International Nuclear Information System (INIS)

    Salmela, Olli

    2005-01-01

    In this paper, the dependability of 3rd generation telecommunications network systems is studied. Special attention is paid to a case where increased-reliability-risk electronic components are introduced to the system. The paper consists of three parts: First, the reliability data of four electronic components is considered. This includes statistical analysis of the reliability test data, thermo-mechanical finite element analysis of the printed wiring board structures, and based on those, a field reliability estimate of the components is constructed. Second, the component level reliability data is introduced into the network element reliability analysis. This is accomplished by using a reliability block diagram technique and Monte Carlo simulation of the network element. The end result of the second part is a reliability estimate of the network element with and without the high-risk component. Third, the whole 3rd generation network having multiple network elements is analyzed. In this part, the criticality of introducing high-risk electronic components into a 3rd generation telecommunications network is considered

  17. The effect of introducing increased-reliability-risk electronic components into 3rd generation telecommunications systems

    Energy Technology Data Exchange (ETDEWEB)

    Salmela, Olli [Nokia Networks, P.O. Box 301, 00045 Nokia Group (Finland)]. E-mail: olli.salmela@nokia.com

    2005-08-01

    In this paper, the dependability of 3rd generation telecommunications network systems is studied. Special attention is paid to a case where increased-reliability-risk electronic components are introduced to the system. The paper consists of three parts: First, the reliability data of four electronic components is considered. This includes statistical analysis of the reliability test data, thermo-mechanical finite element analysis of the printed wiring board structures, and based on those, a field reliability estimate of the components is constructed. Second, the component level reliability data is introduced into the network element reliability analysis. This is accomplished by using a reliability block diagram technique and Monte Carlo simulation of the network element. The end result of the second part is a reliability estimate of the network element with and without the high-risk component. Third, the whole 3rd generation network having multiple network elements is analyzed. In this part, the criticality of introducing high-risk electronic components into a 3rd generation telecommunications network is considered.

  18. [Occurrence of associated tumours in chronic lymphocytic leukemia].

    Science.gov (United States)

    Szerafin, László; Jakó, János; Varju, Lóránt

    2016-10-01

    Chronic lymphocytic leukemia is one of the most common hematologic malignancy. The aim of the authors was to investigate the characteristics of malignancies associated with chronic lymphocytic leukemia in patients diagnozed between 2000 and 2015. Data of patients with chronic lymphocytic leukemia who had other associated tumours were analysed using the Leukemia/Lymphoma Registry of the Szabolcs-Szatmár-Bereg County, Hungary and patient records. Between January 1, 2000 and December 31, 2015, 526 patients with chronic lymphocytic leukemia were diagnosed. 95 patients of the 526 patients (18.06%) were diagnosed as having associated other tumours. In 48/95 patients (50.5%) the first diagnosed tumour was chronic lymphocytic leukemia, in 23/95 patients (24.2%) the first recognized malignancy was the associated tumour, whereas in 24/95 patients (25.3%) synchron tumours were diagnosed. The number of patients with more than one associated tumour was 10/95 (10.5%). The total number of tumours was 107. The incidence of chronic lymphoid leukemia increased in the period between 2000 and 2015 as compared to the period between 1983 and 1999 (3.19 vs 5.65/100 000 person/year). The occurrence of associated malignancies increased as well (8.06% vs 18.06%). In addition to the most common tumours (colorectal, breast, lung, prostate), skin squamous cell carcinoma (17/95 patients; 17.9%) and melanoma (6/95 patients; 6.3%) also frequently occurred. The second malignancies were most frequently discovered after the diagnosis of chronic lymphocytic leukemia and synchron tumours accounting for 78.5% (84/107) of all associated tumours. The incidence of second malignancies decreased 10 years after the diagnosis of chronic lymphocytic leukemia. The possible reasons for the high frequency of other tumours associated with chronic lymphocytic leukemia are elderly age of patients, immunsuppressed state and, presumably, chemotherapy of patients with chronic lymphocytic leukemia. During the follow up

  19. Implementation of transparency and accountability under risk-based audit of electronic procurement system

    Directory of Open Access Journals (Sweden)

    M.S. Pysmenna

    2017-08-01

    Full Text Available The research analyzes the international norms and practice of realization of the purpose of state audit authorities. It is established that the activities of the state audit are aimed at improving the lives of citizens, and for this purpose the control authority, through the implementation of the principles, should achieve the goals of strengthening the principles of accountability, transparency and integrity in government and public institutions, demonstrating constant importance for citizens, parliament and other stakeholders, maintaining integrity. The study of domestic legislation on state audit in relation to compliance with international norms is conducted; the gaps and inconsistencies regarding compliance with the basic principles of transparency and accountability that ensure the purpose of the control authority activities are identified. It is determined that in order to formulate reports on the results of public procurement audits for informing the public, it is necessary to improve and apply a broader methodology of risk-based audit. The article investigates the preconditions and identifies the risks of the electronic procurement system, provides their characteristics and identifies the areas, which are negatively affected by the risks. The author identifies the information components and management functions that cannot be performed qualitatively because of the existence of risks and threats; the author also specifies the procedures for internal control over the process of administration of public procurement, and if the procedures are faced with failure, it increases the identified risks. It is proved that the proposed method of identification and evaluation of the risks of the electronic public procurement system can be used not only as a verification tool but also as the basis for compilation of reports due to the grouping of violations of the negative consequences of risks for the functioning of the system. This will ensure the

  20. Transfer of ERR for radiation-related leukemia from Japanese population to Chinese population

    International Nuclear Information System (INIS)

    Huang Liqiong; Sun Zhijuan; Zhao Yongcheng; Wang Jixian

    2011-01-01

    Objective: To establish a transfer model for excess relative risk (ERR) for radiation-related leukemia from Japanese population to Chinese population. Methods: Combined ERR of several subtypes of leukemia published in 1994, with the corresponding leukemia baseline incidence rates obtained from Cancer Incidence in Five Continents Vol. Ⅸ (CI5-Ⅸ) for Japanese population and Chinese population, a weighted risk transfer model was employed between an additive model and a multiplicative model, to execute ERR transfer. Results: A range of weighing factors was proposed for risk transfer models: weighing factor was 0.4 for male and 0.3 for female, acute lymphoblastic leukemia, acute myeloid leukemia and chronic myeloid leukemia. The uncertainty for ERR transfer was characterized by lognormal distribution. Conclusions: Based on the difference of baseline incidence rate for subtypes of leukemia between Japanese population and Chinese population, the transfer model and these weighing factors discussed in the present study could be applicable to transfer ERR for radiation-related leukemia from Japanese population to Chinese population. (authors)

  1. Leukemia in patients following radiotherapy for malignant neoplasms in the pelvic region

    Energy Technology Data Exchange (ETDEWEB)

    Murohashi, Ikuo

    1985-01-01

    A prospective study of 1572 women treated with radiotherapy for cervical (1478 women) and ovarian cancer (95 women) was done. Patients had been followed clinically and especially by blood tests between 1961 and 1981, comprising 8990 women-years (WY). Following radiotherapy, 5 patients developed non-lymphocytic leukemia (2 acute myeloblastic leukemia (AML), 1 acute monocytic leukemia (AMoL), and 2 chronic myeloid leukemia (CML)). Based on rates for the general population, 0.45 case would be expected, and, therefore, the relative risk was 11.2. The average mean marrow dose for all our subjects was calculated to be 11.77 rad, the risk of radiation-induced leukemia was 0.43 excess case per year per one million women exposed to 1 rad of radiation to the bone marrow. Four patients with cervical cancer who developed leukemia were in a high-dose-rate group treated with both a linear accelerator (Linac) and remote afterloading system (RALS), and 1 patient with ovarian cancer who developed leukemia was treated with a Linac alone. This is the first report of a statistically significant increased risk of leukemia for patients treated with large doses of radiation for malignant neoplasms in the pelvic region. (author).

  2. Leukemia in patients following radiotherapy for malignant neoplasms in the pelvic region

    International Nuclear Information System (INIS)

    Murohashi, Ikuo

    1985-01-01

    A prospective study of 1572 women treated with radiotherapy for cervical (1478 women) and ovarian cancer (95 women) was done. Patients had been followed clinically and especially by blood tests between 1961 and 1981, comprising 8990 women-years (WY). Following radiotherapy, 5 patients developed non-lymphocytic leukemia [2 acute myeloblastic leukemia (AML), 1 acute monocytic leukemia (AMoL), and 2 chronic myeloid leukemia (CML)]. Based on rates for the general population, 0.45 case would be expected, and, therefore, the relative risk was 11.2. The average mean marrow dose for all our subjects was calculated to be 11.77 rad, the risk of radiation-induced leukemia was 0.43 excess case per year per one million women exposed to 1 rad of radiation to the bone marrow. Four patients with cervical cancer who developed leukemia were in a high-dose-rate group treated with both a linear accelerator (Linac) and remote afterloading system (RALS), and 1 patient with ovarian cancer who developed leukemia was treated with a Linac alone. This is the first report of a statistically significant increased risk of leukemia for patients treated with large doses of radiation for malignant neoplasms in the pelvic region. (author)

  3. Extramedullary leukemia in children with acute myeloid leukemia

    DEFF Research Database (Denmark)

    Støve, Heidi Kristine; Sandahl, Julie Damgaard; Abrahamsson, Jonas

    2017-01-01

    BACKGROUND: The prognostic significance of extramedullary leukemia (EML) in childhood acute myeloid leukemia is not clarified. PROCEDURE: This population-based study included 315 children from the NOPHO-AML 2004 trial. RESULTS: At diagnosis, 73 (23%) patients had EML: 39 (12%) had myeloid sarcoma...... the OS. No patients relapsed at the primary site of the myeloid sarcoma despite management without radiotherapy....

  4. Enabling More than Moore: Accelerated Reliability Testing and Risk Analysis for Advanced Electronics Packaging

    Science.gov (United States)

    Ghaffarian, Reza; Evans, John W.

    2014-01-01

    For five decades, the semiconductor industry has distinguished itself by the rapid pace of improvement in miniaturization of electronics products-Moore's Law. Now, scaling hits a brick wall, a paradigm shift. The industry roadmaps recognized the scaling limitation and project that packaging technologies will meet further miniaturization needs or ak.a "More than Moore". This paper presents packaging technology trends and accelerated reliability testing methods currently being practiced. Then, it presents industry status on key advanced electronic packages, factors affecting accelerated solder joint reliability of area array packages, and IPC/JEDEC/Mil specifications for characterizations of assemblies under accelerated thermal and mechanical loading. Finally, it presents an examples demonstrating how Accelerated Testing and Analysis have been effectively employed in the development of complex spacecraft thereby reducing risk. Quantitative assessments necessarily involve the mathematics of probability and statistics. In addition, accelerated tests need to be designed which consider the desired risk posture and schedule for particular project. Such assessments relieve risks without imposing additional costs. and constraints that are not value added for a particular mission. Furthermore, in the course of development of complex systems, variances and defects will inevitably present themselves and require a decision concerning their disposition, necessitating quantitative assessments. In summary, this paper presents a comprehensive view point, from technology to systems, including the benefits and impact of accelerated testing in offsetting risk.

  5. Improving prediction of fall risk among nursing home residents using electronic medical records.

    Science.gov (United States)

    Marier, Allison; Olsho, Lauren E W; Rhodes, William; Spector, William D

    2016-03-01

    Falls are physically and financially costly, but may be preventable with targeted intervention. The Minimum Data Set (MDS) is one potential source of information on fall risk factors among nursing home residents, but its limited breadth and relatively infrequent updates may limit its practical utility. Richer, more frequently updated data from electronic medical records (EMRs) may improve ability to identify individuals at highest risk for falls. The authors applied a repeated events survival model to analyze MDS 3.0 and EMR data for 5129 residents in 13 nursing homes within a single large California chain that uses a centralized EMR system from a leading vendor. Estimated regression parameters were used to project resident fall probability. The authors examined the proportion of observed falls within each projected fall risk decile to assess improvements in predictive power from including EMR data. In a model incorporating fall risk factors from the MDS only, 28.6% of observed falls occurred among residents in the highest projected risk decile. In an alternative specification incorporating more frequently updated measures for the same risk factors from the EMR data, 32.3% of observed falls occurred among residents in the highest projected risk decile, a 13% increase over the base MDS-only specification. Incorporating EMR data improves ability to identify those at highest risk for falls relative to prediction using MDS data alone. These improvements stem chiefly from the greater frequency with which EMR data are updated, with minimal additional gains from availability of additional risk factor variables. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Cytomorphology review of 100 newly diagnosed lower-risk MDS patients in the European LeukemiaNet MDS (EUMDS) registry reveals a high inter-observer concordance.

    Science.gov (United States)

    de Swart, Louise; Smith, Alex; MacKenzie, Marius; Symeonidis, Argiris; Neukirchen, Judith; Mikulenková, Dana; Vallespí, Teresa; Zini, Gina; Paszkowska-Kowalewska, Malgorzata; Kruger, Anton; Saft, Leonie; Fenaux, Pierre; Bowen, David; Hellström-Lindberg, Eva; Čermák, Jaroslav; Stauder, Reinhard; Tatic, Aurelia; Holm, Mette Skov; Malcovati, Luca; Mądry, Krzysztof; Droste, Jackie; Blijlevens, Nicole; de Witte, Theo; Germing, Ulrich

    2017-07-01

    The European LeukemiaNet MDS (EUMDS) registry is collecting data of myelodysplastic syndrome (MDS) patients belonging to the IPSS low or intermediate-1 category, newly diagnosed by local cytologists. The diagnosis of MDS can be challenging, and some data report inter-observer variability with regard to the assessment of the MDS subtype. In order to ensure that correct diagnoses were made by the participating centres, blood and bone marrow slides of 10% of the first 1000 patients were reviewed by an 11-person panel of cytomorphologists. All slides were rated by at least 3 panel members (median 8 panel members; range 3-9). Marrow slides from 98 out of 105 patients were of good quality and therefore could be rated properly according to the WHO 2001 classification, including assessment of dysplastic lineages. The agreement between the reviewers whether the diagnosis was MDS or non-MDS was strong with an intra-class correlation coefficient (ICC) of 0.85. Six cases were detected not to fit the entry criteria of the registry, because they were diagnosed uniformly as CMML or AML by the panel members. The agreement by WHO 2001 classification was strong as well (ICC = 0.83). The concordance of the assessment of dysplastic lineages was substantial for megakaryopoiesis and myelopoiesis and moderate for erythropoiesis. Our data show that in general, the inter-observer agreement was high and a very low percentage of misdiagnosed cases had been entered into the EUMDS registry. Further studies including histomorphology are warranted.

  7. Sequence analysis of Leukemia DNA

    Science.gov (United States)

    Nacong, Nasria; Lusiyanti, Desy; Irawan, Muhammad. Isa

    2018-03-01

    Cancer is a very deadly disease, one of which is leukemia disease or better known as blood cancer. The cancer cell can be detected by taking DNA in laboratory test. This study focused on local alignment of leukemia and non leukemia data resulting from NCBI in the form of DNA sequences by using Smith-Waterman algorithm. SmithWaterman algorithm was invented by TF Smith and MS Waterman in 1981. These algorithms try to find as much as possible similarity of a pair of sequences, by giving a negative value to the unequal base pair (mismatch), and positive values on the same base pair (match). So that will obtain the maximum positive value as the end of the alignment, and the minimum value as the initial alignment. This study will use sequences of leukemia and 3 sequences of non leukemia.

  8. High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

    Science.gov (United States)

    2018-02-28

    Acute Leukemia of Ambiguous Lineage; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  9. Randomized Phase II Study of Azacitidine Alone or in Combination With Lenalidomide or With Vorinostat in Higher-Risk Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia: North American Intergroup Study SWOG S1117.

    Science.gov (United States)

    Sekeres, Mikkael A; Othus, Megan; List, Alan F; Odenike, Olatoyosi; Stone, Richard M; Gore, Steven D; Litzow, Mark R; Buckstein, Rena; Fang, Min; Roulston, Diane; Bloomfield, Clara D; Moseley, Anna; Nazha, Aziz; Zhang, Yanming; Velasco, Mario R; Gaur, Rakesh; Atallah, Ehab; Attar, Eyal C; Cook, Elina K; Cull, Alyssa H; Rauh, Michael J; Appelbaum, Frederick R; Erba, Harry P

    2017-08-20

    Purpose Azacitidine is standard, first-line therapy in higher-risk myelodysplastic syndromes (MDS). Whether azacitidine-based combinations with lenalidomide or vorinostat produce superior overall response rates (ORRs) to azacitidine is not known. Patients and Methods North American Intergroup Study S1117 is a phase II/III trial that randomly assigned patients with higher-risk MDS and chronic myelomonocytic leukemia (CMML) 1:1:1 to azacitidine (75 mg/m 2 /day on days 1 to 7 of a 28-day cycle); azacitidine plus lenalidomide (10 mg/day on days 1 to 21); or azacitidine plus vorinostat (300 mg twice daily on days 3 to 9). The primary phase II end point was improved ORR. Results Of 277 patients from 90 centers, 92 received azacitidine, 93 received azacitidine plus lenalidomide, and 92 received azacitidine plus vorinostat. Median age was 70 years (range, 28 to 93 years), 85 patients (31%) were female, and 53 patients (19%) had CMML. Serious adverse events were similar across arms, although combination-arm patients were more likely to undergo nonprotocol-defined dose modifications ( P vorinostat ( P = .16 v azacitidine). For patients with CMML, ORR was higher for azacitidine plus lenalidomide versus azacitidine (68% v 28%, P = .02) but similar for all arms across cytogenetic subgroups, as was remission duration and overall survival. ORR was higher with mutations in DNMT3A and lower for SRSF2, whereas ORR duration improved with fewer mutations. Lenalidomide dose reduction was associated with worse overall survival (hazard ratio, 1.30; P = .05). Conclusion Patients with higher-risk MDS treated with azacitidine-based combinations had similar ORR to azacitidine monotherapy, although patients with CMML benefitted from azacitidine plus lenalidomide. The efficacy of combination regimens may have been affected by dose modifications.

  10. Perceived quality, perceived risk and customer trust affecting customer loyalty of environmentally friendly electronics products

    Directory of Open Access Journals (Sweden)

    Lalinthorn Marakanon

    2017-01-01

    Full Text Available At present, industrial business competition causes producers to be aware of quality, price, and variety in developing new products to meet the consumers' needs. This research reviewed the literature on green marketing and proposes a new conceptual framework of customer loyalty. It uses four constructs—perceived quality, perceived risk, customer trust, and customer loyalty—in the context of environmentally friendly electronics products in Thailand. This research employed an empirical study using the questionnaire survey method to verify the hypotheses. Data were obtained from 420 consumers who bought and used environmentally friendly electronic products, particularly mobile phones, computers, and laptops using a purposive sampling method. The data were analyzed using confirmatory factor analysis (CFA and structural equation modeling (SEM. The results showed that perceived risk and customer trust had a direct effect on customer loyalty while perceived quality had an indirect effect on customer loyalty via customer trust. Furthermore, perceived quality had direct effects on perceived risk and customer trust. The results from the final SEM model were used to confirm the proposed relationships among the variables.

  11. Risk factors for radiotherapy incidents and impact of an online electronic reporting system

    International Nuclear Information System (INIS)

    Chang, David W.; Cheetham, Lynn; Marvelde, Luc te; Bressel, Mathias; Kron, Tomas; Gill, Suki; Tai, Keen Hun; Ball, David; Rose, William; Silva, Linas; Foroudi, Farshad

    2014-01-01

    Background and purpose: To ascertain the rate, type, significance, trends and the potential risk factors associated with radiotherapy incidents in a large academic department. Materials and methods: Data for all radiotherapy activities from July 2001 to January 2011 were reviewed from radiotherapy incident reporting forms. Patient and treatment data were obtained from the radiotherapy record and verification database (MOSAIQ) and the patient database (HOSPRO). Logistic regression analyses were performed to determine variables associated with radiotherapy incidents. Results: In that time, 65,376 courses of radiotherapy were delivered with a reported incident rate of 2.64 per 100 courses. The rate of incidents per course increased (1.96 per 100 courses to 3.52 per 100 courses, p < 0.001) whereas the proportion of reported incidents resulting in >5% deviation in dose (10.50 to 2.75%, p < 0.001) had decreased after the introduction of an online electronic reporting system. The following variables were associated with an increased rate of incidents: afternoon treatment time, paediatric patients, males, inpatients, palliative plans, head-and-neck, skin, sarcoma and haematological malignancies. In general, complex plans were associated with higher incidence rates. Conclusion: Radiotherapy incidents were infrequent and most did not result in significant dose deviation. A number of risk factors were identified and these could be used to highlight high-risk cases in the future. Introduction of an online electronic reporting system resulted in a significant increase in the number of incidents being reported

  12. Vorinostat in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2014-04-30

    Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  13. Identifying primary care patients at risk for future diabetes and cardiovascular disease using electronic health records

    Directory of Open Access Journals (Sweden)

    Shrader Peter

    2009-09-01

    Full Text Available Abstract Background Prevention of diabetes and coronary heart disease (CHD is possible but identification of at-risk patients for targeting interventions is a challenge in primary care. Methods We analyzed electronic health record (EHR data for 122,715 patients from 12 primary care practices. We defined patients with risk factor clustering using metabolic syndrome (MetS characteristics defined by NCEP-ATPIII criteria; if missing, we used surrogate characteristics, and validated this approach by directly measuring risk factors in a subset of 154 patients. For subjects with at least 3 of 5 MetS criteria measured at baseline (2003-2004, we defined 3 categories: No MetS (0 criteria; At-risk-for MetS (1-2 criteria; and MetS (≥ 3 criteria. We examined new diabetes and CHD incidence, and resource utilization over the subsequent 3-year period (2005-2007 using age-sex-adjusted regression models to compare outcomes by MetS category. Results After excluding patients with diabetes/CHD at baseline, 78,293 patients were eligible for analysis. EHR-defined MetS had 73% sensitivity and 91% specificity for directly measured MetS. Diabetes incidence was 1.4% in No MetS; 4.0% in At-risk-for MetS; and 11.0% in MetS (p MetS vs No MetS = 6.86 [6.06-7.76]; CHD incidence was 3.2%, 5.3%, and 6.4% respectively (p Conclusion Risk factor clustering in EHR data identifies primary care patients at increased risk for new diabetes, CHD and higher resource utilization.

  14. Childhood CT scans linked to leukemia and brain cancer later in life

    Science.gov (United States)

    Children and young adults scanned multiple times by computed tomography (CT), a commonly used diagnostic tool, have a small increased risk of leukemia and brain tumors in the decade following their first scan.

  15. Risk mitigation of shared electronic records system in campus institutions: medical social work practice in singapore.

    Science.gov (United States)

    Ow Yong, Lai Meng; Tan, Amanda Wei Li; Loo, Cecilia Lay Keng; Lim, Esther Li Ping

    2014-10-01

    In 2013, the Singapore General Hospital (SGH) Campus initiated a shared electronic system where patient records and documentations were standardized and shared across institutions within the Campus. The project was initiated to enhance quality of health care, improve accessibility, and ensure integrated (as opposed to fragmented) care for best outcomes in our patients. In mitigating the risks of ICT, it was found that familiarity with guiding ethical principles, and ensuring adherence to regulatory and technical competencies in medical social work were important. The need to negotiate and maneuver in a large environment within the Campus to ensure proactive integrative process helped.

  16. Leukemia among atomic bomb survivors during the 1980s

    International Nuclear Information System (INIS)

    Kusumi, Shizuyo; Matsuo, Tatsuki

    1990-01-01

    On the basis of the dosimetry system 1986, exposure doses were determined in a cohort of 86,502 subjects for the Life Span Study during the period 1950-1985. A total of 248 people were found to develop leukemia in Hiroshima and Nagasaki cities. This is an analysis of the 248 patients with leukemia in connection with exposure doses, years after A-bombing, age at the time of A-bombing, relative risk, and background. An average exposure dose was 0.20 Gy for Hiroshima and 0.22 Gy for Nagasaki. Relative risk for leukemia tended to show a linear increase in proportion to exposure doses. This was significant for acute myelocytic leukemia (AML), regardless of whether A-bomb survivors came from Hiroshima or Nagasaki. The younger the age at the time of A-bombing was, the higher excess relative risk for acute lymphocytic leukemia (ALL) and chronic myelocytic leukemia (CML) was. For AML, however, it was independent of the age at that time. These findings were similar in Hiroshima and Nagasaki A-bomb survivors, irrespective of age. As for non-exposed group, the incidence of CML was three times higher in Hiroshima citizen than Nagasaki citizen. Similarly, Hiroshima citizen had a 1.6 fold incidence of AML. There was no significant difference in the incidence of ALL between the cities. The incidences of both AML and ALL tended to increase more and more with aging, but the prevalences tended to increase in younger generation. An increased incidence of CML was associated with aging alone. (N.K.)

  17. Occupational exposure to solvents and acute myeloid leukemia

    DEFF Research Database (Denmark)

    Talibov, Madar; Lehtinen-Jacks, Susanna; Martinsen, Jan Ivar

    2014-01-01

    OBJECTIVE: The aim of the current study was to assess the relation between occupational exposure to solvents and the risk of acute myeloid leukemia (AML). METHODS: Altogether, this study comprises 15 332 incident cases of AML diagnosed in Finland, Norway, Sweden and Iceland from 1961-2005 and 76...

  18. Etiology of common childhood acute lymphoblastic leukemia: the adrenal hypothesis

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Vestergaard, T.; Nielsen, S.M.

    2008-01-01

    The pattern of infections in the first years of life modulates our immune system, and a low incidence of infections has been linked to an increased risk of common childhood acute lymphoblastic leukemia (ALL). We here present a new interpretation of these observations--the adrenal hypothesis...

  19. Neurodevelopmental Sequelae of Pediatric Acute Lymphoblastic Leukemia and Its Treatment

    Science.gov (United States)

    Janzen, Laura A.; Spiegler, Brenda J.

    2008-01-01

    This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research.…

  20. Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Levinsen, Mette Frandsen; Attarbaschi, Andishe

    2013-01-01

    PURPOSE: Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. PATIENTS AND METHODS: We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 19...

  1. Acute lymphoblastic leukemia in children with Down syndrome

    DEFF Research Database (Denmark)

    Buitenkamp, Trudy D; Izraeli, Shai; Zimmermann, Martin

    2014-01-01

    Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995...

  2. A Comparative Health Risk Assessment of Electronic Cigarettes and Conventional Cigarettes

    Directory of Open Access Journals (Sweden)

    Jinsong Chen

    2017-04-01

    Full Text Available Background: Although some studies have identified hazardous substances in electronic cigarette (EC liquids and emissions, there is limited information about the health risks of using ECs. Methods: In this study, the U.S. Environmental Protection Agency (EPA health risk assessment model and findings of a literature review were used to determine and profile hazards. Focus was put on the toxicants reported in the literature on conventional cigarette (CC smoke that most strongly associated with adverse health effects. To evaluate their health risks, dose-response relationships and standard-use conditions were used to estimate average hazard exposures and to calculate the overall health risks of ECs and CCs, benchmarked against international guideline levels for each hazard. Results: Four hazards (acrolein, diethylene glycol, propylene glycol and cadmium reported in EC emissions and seven hazards (acetaldehyde, acrolein, formaldehyde, cadmium, CO, 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK, N′-nitrosonornicotine (NNN reported in CC emissions had maximum exposure levels higher than the guideline levels. Two hazards (acrolein, propylene glycol in EC emissions and five hazards (acetaldehyde, acrolein, formaldehyde, cadmium, NNN in CC emissions had average exposure levels higher than the guideline levels. Conclusions: Based on the conditions of use, ECs should be a safer nicotine-delivery product than CCs.

  3. Coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma with antecedent chronic lymphocytic leukemia: a case report and review of the literature.

    Science.gov (United States)

    Abuelgasim, Khadega A; Rehan, Hinna; Alsubaie, Maha; Al Atwi, Nasser; Al Balwi, Mohammed; Alshieban, Saeed; Almughairi, Areej

    2018-03-11

    Chronic lymphocytic leukemia and chronic myeloid leukemia are the most common types of adult leukemia. However, it is rare for the same patient to suffer from both. Richter's transformation to diffuse large B-cell lymphoma is frequently observed in chronic lymphocytic leukemia. Purine analog therapy and the presence of trisomy 12, and CCND1 gene rearrangement have been linked to increased risk of Richter's transformation. The coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma in the same patient is extremely rare, with only nine reported cases. Here, we describe the first reported case of concurrent chronic myeloid leukemia and diffuse large B-cell lymphoma in a background of chronic lymphocytic leukemia. A 60-year-old Saudi man known to have diabetes, hypertension, and chronic active hepatitis B was diagnosed as having Rai stage II chronic lymphocytic leukemia, with trisomy 12 and rearrangement of the CCND1 gene in December 2012. He required no therapy until January 2016 when he developed significant anemia, thrombocytopenia, and constitutional symptoms. He received six cycles of fludarabine, cyclophosphamide, and rituximab, after which he achieved complete remission. One month later, he presented with progressive leukocytosis (mostly neutrophilia) and splenomegaly. Fluorescence in situ hybridization from bone marrow aspirate was positive for translocation (9;22) and reverse transcription polymerase chain reaction detected BCR-ABL fusion gene consistent with chronic myeloid leukemia. He had no morphologic or immunophenotypic evidence of chronic lymphocytic leukemia at the time. Imatinib, a first-line tyrosine kinase inhibitor, was started. Eight months later, a screening imaging revealed new liver lesions, which were confirmed to be diffuse large B-cell lymphoma. In chronic lymphocytic leukemia, progressive leukocytosis and splenomegaly caused by emerging chronic myeloid leukemia can be easily overlooked. It is unlikely that chronic myeloid

  4. Leukemia and other cancers after radiotherapy and chemotherapy for Hodgkin's disease

    International Nuclear Information System (INIS)

    Boivin, J.F.; Hutchison, G.B.

    1981-01-01

    A cohort study designed to evaluate the carcinogenicity of treatment for Hodgkin's disease (HD) was begun in 1976. This report describes 1,553 patients diagnosed with HD in 1940-75 and presents an analysis of follow-up findings through 1976. Twenty-seven cancers (excluding basal cell and squamous cell carcinomas of skin, trichoepitheliomas, and in situ carcinomas of cervix uteri) were observed 1 year or more after diagnosis of HD, including 6 leukemias. The relative risk (RR) of leukemia in patients treated with intensive chemotherapy with or without radiotherapy relative to general population incidence rates was 140 (95% confidence limits: 50,300). In the subgroup treated with both intensive radiotherapy and intensive chemotherapy, the RR of leukemia was 270 (95% confidence limits: 56,800). No leukemia occurred after treatment with intensive radiotherapy without chemotherapy. For cancers other than leukemia and for non-HD lymphomas, RR was generally not significantly different from the null value one

  5. Effective chemotherapy of acute myelocytic leukemia occurring after alkylating agent or radiation therapy for prior malignancy

    International Nuclear Information System (INIS)

    Vaughan, W.P.; Karp, J.E.; Burke, P.J.

    1983-01-01

    Eleven consecutive patients with acute myelocytic leukemia occurring as a second malignancy were treated with high-dose, timed, sequential chemotherapy. Eight of the patients were felt to have ''secondary'' acute leukemia because they had received an alkylating agent or radiation therapy. The other three patients were considered controls. Despite a median age of 65, four of the eight secondary leukemia patients achieved complete remission with this regimen. One of the three control patients also achieved complete remission. This remission rate and duration are comparable to what was achieved with this treatment of ''primary'' acute myelocytic leukemia during the same period of time. These results suggest that patients with leukemia occurring after an alkylating agent or radiation therapy are not at especially high risk if treated aggressively

  6. Molecular epidemiology of acute leukemia in children: causal model, interaction of three factors-susceptibility, environmental exposure and vulnerability period.

    Science.gov (United States)

    Mejía-Aranguré, Juan Manuel

    Acute leukemias have a huge morphological, cytogenetic and molecular heterogeneity and genetic polymorphisms associated with susceptibility. Every leukemia presents causal factors associated with the development of the disease. Particularly, when three factors are present, they result in the development of acute leukemia. These phenomena are susceptibility, environmental exposure and a period that, for this model, has been called the period of vulnerability. This framework shows how the concepts of molecular epidemiology have established a reference from which it is more feasible to identify the environmental factors associated with the development of leukemia in children. Subsequently, the arguments show that only susceptible children are likely to develop leukemia once exposed to an environmental factor. For additional exposure, if the child is not susceptible to leukemia, the disease does not develop. In addition, this exposure should occur during a time window when hematopoietic cells and their environment are more vulnerable to such interaction, causing the development of leukemia. This model seeks to predict the time when the leukemia develops and attempts to give a context in which the causality of childhood leukemia should be studied. This information can influence and reduce the risk of a child developing leukemia. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  7. 32P and acute leukemia: development of leukemia in a patient with hemoglobin Yakima

    International Nuclear Information System (INIS)

    Bagby, G.C. Jr.; Richert-Boe, K.; Koler, R.D.

    1978-01-01

    In 1954 a then 31-yr-old male was found to have erythrocytosis. Over the ensuing decade he received 72 mCi 32 P. In 1964 his daughters were found to have erythrocytosis. Further investigation led to the discovery of hemoglobin Yakima, a variant with high oxygen affinity. He received no further therapy and was well until 1975, when he developed the preleukemic syndrome. Within 12 mo he developed acute nonlymphocytic leukemia accompanied by fetal erythropoiesis. Because the initial discovery of this type of hemoglobinopathy came 27 yr after the introduction of 32 P for use in the treatment of polycythemia vera, and because there are now known to be more than 39 different high-oxygen-affinity hemoglobins, we anticipate that more patients such as ours have been exposed to 32 P. The exposed population should be closely followed, since this will likely permit assessment of the risk of 32 P-induced leukemia in a nonneoplastic condition

  8. The MLL recombinome of acute leukemias in 2013

    Science.gov (United States)

    Meyer, C; Hofmann, J; Burmeister, T; Gröger, D; Park, T S; Emerenciano, M; Pombo de Oliveira, M; Renneville, A; Villarese, P; Macintyre, E; Cavé, H; Clappier, E; Mass-Malo, K; Zuna, J; Trka, J; De Braekeleer, E; De Braekeleer, M; Oh, S H; Tsaur, G; Fechina, L; van der Velden, V H J; van Dongen, J J M; Delabesse, E; Binato, R; Silva, M L M; Kustanovich, A; Aleinikova, O; Harris, M H; Lund-Aho, T; Juvonen, V; Heidenreich, O; Vormoor, J; Choi, W W L; Jarosova, M; Kolenova, A; Bueno, C; Menendez, P; Wehner, S; Eckert, C; Talmant, P; Tondeur, S; Lippert, E; Launay, E; Henry, C; Ballerini, P; Lapillone, H; Callanan, M B; Cayuela, J M; Herbaux, C; Cazzaniga, G; Kakadiya, P M; Bohlander, S; Ahlmann, M; Choi, J R; Gameiro, P; Lee, D S; Krauter, J; Cornillet-Lefebvre, P; Te Kronnie, G; Schäfer, B W; Kubetzko, S; Alonso, C N; zur Stadt, U; Sutton, R; Venn, N C; Izraeli, S; Trakhtenbrot, L; Madsen, H O; Archer, P; Hancock, J; Cerveira, N; Teixeira, M R; Lo Nigro, L; Möricke, A; Stanulla, M; Schrappe, M; Sedék, L; Szczepański, T; Zwaan, C M; Coenen, E A; van den Heuvel-Eibrink, M M; Strehl, S; Dworzak, M; Panzer-Grümayer, R; Dingermann, T; Klingebiel, T; Marschalek, R

    2013-01-01

    Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (∼90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements. PMID:23628958

  9. Analysis of the leukemia cases occurrence at Vauhallan (Essonne)

    International Nuclear Information System (INIS)

    2005-01-01

    The researches and environmental measurements realised at Vauhallan did not allow to assume a link between an environmental exposure of the population and the occurrence of the two cases of leukemia. In the lack of new hypothesis, the technical group has decided to not pursue the local investigations but to keep, at systematic title, the sanitary surveillance of the commune by a regular questioning of the national register of children leukemia and lymphomas. it is to notice that only studies at a broader scale , as the three national studies of I.n.s.e.r.m., actually running, are in a position to bring new knowledge on the risk factors of children leukemia as well their spatial distribution. (N.C.)

  10. Association of ARID5B gene variants with acute lymphoblastic leukemia in Yemeni children.

    Science.gov (United States)

    Al-Absi, Boshra; Noor, Suzita M; Saif-Ali, Riyadh; Salem, Sameer D; Ahmed, Radwan H; Razif, Muhammad Fm; Muniandy, Sekaran

    2017-04-01

    Studies have shown an association between ARID5B gene polymorphisms and childhood acute lymphoblastic leukemia. However, the association between ARID5B variants and acute lymphoblastic leukemia among the Arab population still needs to be studied. The aim of this study was to investigate the association between ARID5B variants with acute lymphoblastic leukemia in Yemeni children. A total of 14 ARID5B gene single nucleotide polymorphisms (SNPs) were genotyped in 289 Yemeni children, of whom 136 had acute lymphoblastic leukemia and 153 were controls, using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Using logistic regression adjusted for age and gender, the risks of acute lymphoblastic leukemia were presented as odds ratios and 95% confidence intervals. We found that nine SNPs were associated with acute lymphoblastic leukemia under additive genetic models: rs7073837, rs10740055, rs7089424, rs10821936, rs4506592, rs10994982, rs7896246, rs10821938, and rs7923074. Furthermore, the recessive models revealed that six SNPs were risk factors for acute lymphoblastic leukemia: rs10740055, rs7089424, rs10994982, rs7896246, rs10821938, and rs7923074. The gender-specific impact of these SNPs under the recessive genetic model revealed that SNPs rs10740055, rs10994982, and rs6479779 in females, and rs10821938 and rs7923074 in males were significantly associated with acute lymphoblastic leukemia risk. Under the dominant model, SNPs rs7073837, rs10821936, rs7896246, and rs6479778 in males only showed striking association with acute lymphoblastic leukemia. The additive model revealed that SNPs with significant association with acute lymphoblastic leukemia were rs10821936 (both males and females); rs7073837, rs10740055, rs10994982, and rs4948487 (females only); and rs7089424, rs7896246, rs10821938, and rs7923074 (males only). In addition, the ARID5B haplotype block (CGAACACAA) showed a higher risk for acute lymphoblastic leukemia. The haplotype (CCCGACTGC) was

  11. Expression of HER2/Neu in B-Cell Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Rodriguez-Rodriguez, Sergio; Pomerantz, Alan; Demichelis-Gomez, Roberta; Barrera-Lumbreras, Georgina; Barrales-Benitez, Olga; Aguayo-Gonzalez, Alvaro

    2016-01-01

    The expression of HER2/neu in B-cell acute lymphoblastic leukemia has been reported in previous studies. The objective of this research was to study the expression of HER2/neu on the blasts of patients with acute leukemia from the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. From June 2015 to February 2016, a HER2/neu monoclonal antibody was added to the panel of antibodies that we routinely use in patients with acute leukemia. An expression of ≥ 30% was considered positive. We studied 33 patients: 19 had de novo leukemia (57.6%), three (9.1%) were in relapse, and in 11 (33.3%) their status could not be specified. Seventeen patients (51.5%) were classified as B-cell acute lymphoblastic leukemia with a median expression of HER2/neu of 0.3% (range 0-90.2). Three patients with B-cell acute lymphoblastic leukemia were positive for HER2/neu: 89.4%, 90.9%, and 62.4%. The first and third patient had de novo B-cell acute lymphoblastic leukemia. The second patient was in second relapse after allogeneic stem cell transplant. All three patients were categorized as high-risk at the time of diagnosis. In the studied Mexican population, we found a positive expression of HER2/neu in 17% of the B-cell acute lymphoblastic leukemia patients, similar to previous studies in which the expression was found in 15-50%.

  12. Unusual space-time patterning of the Fallon, Nevada leukemia cluster: Evidence of an infectious etiology.

    Science.gov (United States)

    Francis, Stephen S; Selvin, Steve; Yang, Wei; Buffler, Patricia A; Wiemels, Joseph L

    2012-04-05

    The town of Fallon within Churchill County, Nevada exhibited an unusually high incidence of childhood leukemia during the years 1997-2003. We examined the temporal and spatial patterning of the leukemia case homes in comparison to the distribution of the general population at risk, other cancer incidence, and features of land use. Leukemia cases were predominantly diagnosed during the early to mid summer, exhibiting a seasonal bias. Leukemia cases lived outside of the "developed/urban" area of Fallon, predominantly in the "agriculture/pasture" region of Churchill County, circumscribing downtown Fallon. This pattern was different from the distribution of the underlying population (p-valuespace-time patterning of childhood leukemia is consistent with the involvement of an infectious disease. A possible mode of transmission for such an infectious disease is by means of a vector, and mosquitoes are abundant in Churchill County outside of the urban area of Fallon. This region harbors a US Navy base, and a temporally concordant increase in military wide childhood leukemia rates suggests the base a possible source of the virus. Taken together, our current understanding of the etiology of childhood leukemia, the rural structure combined with temporal and geospatial patterning of these leukemia cases, and the high degree of population mixing in Fallon, suggest a possible infectious cause. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. Childhood leukemia and residential proximity to industrial and urban sites

    International Nuclear Information System (INIS)

    García-Pérez, Javier; López-Abente, Gonzalo; Gómez-Barroso, Diana; Morales-Piga, Antonio; Pardo Romaguera, Elena; Tamayo, Ibon; Fernández-Navarro, Pablo

    2015-01-01

    Background: Few risk factors for the childhood leukemia are well established. While a small fraction of cases of childhood leukemia might be partially attributable to some diseases or ionizing radiation exposure, the role of industrial and urban pollution also needs to be assessed. Objectives: To ascertain the possible effect of residential proximity to both industrial and urban areas on childhood leukemia, taking into account industrial groups and toxic substances released. Methods: We conducted a population-based case–control study of childhood leukemia in Spain, covering 638 incident cases gathered from the Spanish Registry of Childhood Tumors and for those Autonomous Regions with 100% coverage (period 1990-2011), and 13,188 controls, individually matched by year of birth, sex, and autonomous region of residence. Distances were computed from the respective subject’s residences to the 1068 industries and the 157 urban areas with ≥10,000 inhabitants, located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to industrial and urban pollution sources were calculated, with adjustment for matching variables. Results: Excess risk of childhood leukemia was observed for children living near (≤2.5 km) industries (OR=1.31; 95%CI=1.03–1.67) – particularly glass and mineral fibers (OR=2.42; 95%CI=1.49–3.92), surface treatment using organic solvents (OR=1.87; 95%CI=1.24–2.83), galvanization (OR=1.86; 95%CI=1.07–3.21), production and processing of metals (OR=1.69; 95%CI=1.22–2.34), and surface treatment of metals (OR=1.62; 95%CI=1.22–2.15) – , and urban areas (OR=1.36; 95%CI=1.02–1.80). Conclusions: Our study furnishes some evidence that living in the proximity of industrial and urban sites may be a risk factor for childhood leukemia. - Highlights: • We studied proximity to both industrial and urban sites on childhood leukemia. • We conducted a case–control study in

  14. Childhood leukemia and residential proximity to industrial and urban sites

    Energy Technology Data Exchange (ETDEWEB)

    García-Pérez, Javier, E-mail: jgarcia@isciii.es [Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); López-Abente, Gonzalo, E-mail: glabente@isciii.es [Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); Gómez-Barroso, Diana, E-mail: dgomez@externos.isciii.es [CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); Morales-Piga, Antonio, E-mail: amorales@isciii.es [Rare Disease Research Institute (IIER), Carlos III Institute of Health, Madrid (Spain); Consortium for Biomedical Research in Rare Diseases (CIBERER), Madrid (Spain); Pardo Romaguera, Elena, E-mail: elena.pardo@uv.es [Spanish Registry of Childhood Tumors (RETI-SEHOP), University of Valencia, Valencia (Spain); Tamayo, Ibon, E-mail: ibontama@gmail.com [Public Health Division of Gipuzkoa, BIODonostia Research Institute, Department of Health of the Regional Government of the Basque Country, Donostia (Spain); Fernández-Navarro, Pablo, E-mail: pfernandezn@isciii.es [Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); and others

    2015-07-15

    Background: Few risk factors for the childhood leukemia are well established. While a small fraction of cases of childhood leukemia might be partially attributable to some diseases or ionizing radiation exposure, the role of industrial and urban pollution also needs to be assessed. Objectives: To ascertain the possible effect of residential proximity to both industrial and urban areas on childhood leukemia, taking into account industrial groups and toxic substances released. Methods: We conducted a population-based case–control study of childhood leukemia in Spain, covering 638 incident cases gathered from the Spanish Registry of Childhood Tumors and for those Autonomous Regions with 100% coverage (period 1990-2011), and 13,188 controls, individually matched by year of birth, sex, and autonomous region of residence. Distances were computed from the respective subject’s residences to the 1068 industries and the 157 urban areas with ≥10,000 inhabitants, located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to industrial and urban pollution sources were calculated, with adjustment for matching variables. Results: Excess risk of childhood leukemia was observed for children living near (≤2.5 km) industries (OR=1.31; 95%CI=1.03–1.67) – particularly glass and mineral fibers (OR=2.42; 95%CI=1.49–3.92), surface treatment using organic solvents (OR=1.87; 95%CI=1.24–2.83), galvanization (OR=1.86; 95%CI=1.07–3.21), production and processing of metals (OR=1.69; 95%CI=1.22–2.34), and surface treatment of metals (OR=1.62; 95%CI=1.22–2.15) – , and urban areas (OR=1.36; 95%CI=1.02–1.80). Conclusions: Our study furnishes some evidence that living in the proximity of industrial and urban sites may be a risk factor for childhood leukemia. - Highlights: • We studied proximity to both industrial and urban sites on childhood leukemia. • We conducted a case–control study in

  15. Modelling of radiation risk induced by radon and sources of Auger electrons

    International Nuclear Information System (INIS)

    Boem, R.

    2003-01-01

    This thesis follows the national and worldwide radon research and application Auger radionuclides in nuclear medicine. Results of this thesis can be summarised into several points: (1) For the prediction of cancer risk following the exposure, it is also necessary to consider the mean cycle time of target cells. From our analyses it can be concluded that the mean cycle time of target cells should exceed 100 days. (2) The value of excess relative risk is for smokers ERR/WLM = (2.4-4.1)x10 -3 WLM -1 and that of the nonsmokers ERR/WLM=(4.2-10.7)x10 -3 WLM -1 , considering the underground medium. Excess relative risk for the nonsmokers ERR/(Bq m -3 ) = (1.0-3.5) Bq -1 m 3 and for smokers ERR/(Bq m -3 ) = (0.3-1.2) 10 -3 Bq -1 m 3 is supposed in dwellings. (3) Microdosimetric models are very helpful and suitable for prediction of the radon risk for underground conditions, as well as for indoor radon risk evaluation and they are also able to take into account the influence of the smoking habit. (4) The spatial distribution of energy deposition events and their magnitude is an essential input to evaluate the effects of radiation on biological systems. Therefore, for the calculation of deposited energy from the DNA incorporated Auger emitters, it is necessary at the DNA level to employ the MC calculation. In an effort to save computer time and memory it is possible to use the fitted function for monoenergetic electrons for estimation of at least relative radiotoxicity. The value of energy deposited in a small volume (sphere of diameter 2 nm) can be considered as the first estimation of an Auger emitter's radiotoxicity. (author)

  16. Stages of Chronic Lymphocytic Leukemia

    Science.gov (United States)

    ... of the lymph system . Having relatives who are Russian Jews or Eastern European Jews. Signs and symptoms ... information about clinical trials is also available. To Learn More About Chronic Lymphocytic Leukemia For more information ...

  17. Down syndrome preleukemia and leukemia.

    Science.gov (United States)

    Maloney, Kelly W; Taub, Jeffrey W; Ravindranath, Yaddanapudi; Roberts, Irene; Vyas, Paresh

    2015-02-01

    Children with Down syndrome (DS) and acute leukemias acute have unique biological, cytogenetic, and intrinsic factors that affect their treatment and outcome. Myeloid leukemia of Down syndrome (ML-DS) is associated with high event-free survival (EFS) rates and frequently preceded by a preleukemia condition, the transient abnormal hematopoiesis (TAM) present at birth. For acute lymphoblastic leukemia (ALL), their EFS and overall survival are poorer than non-DS ALL, it is important to enroll them on therapeutic trials, including relapse trials; investigate new agents that could potentially improve their leukemia-free survival; and strive to maximize the supportive care these patients need. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Central nervous system in leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Phair, J P; Anderson, R E; Namiki, Hideo

    1964-03-12

    The present report summarizes the pertinent clinical and pathologic findings in 165 cases of leukemia in atomic bomb exposed victims autopsied during the period 1949 to 1962 at ABCC in Hiroshima and Nagasaki, Japan. Significant parenchymal hemorrhage occurred most often in acute myelogenous leukemia and was markedly increased in patients dying with high terminal white blood cell counts. Possible mechanisms involved in the pathogenesis of cerebral hemorrhage in leukemia are discussed. Subarachnoid hemorrhage and subdural hematoma were not related to leukocytosis but appeared to be influenced by marked thrombocytopenia. Leukemic infiltrates of a diffuse nature involving the meninges were paradoxically increased in patients receiving adequate chemotherapy. Meningeal tumors did not show this peculiar relationship to therapy and were not found in association with lymphatic leukemia. Infections involving the central nervous system were confined to patients receiving chemotherapy including steroids. 39 references, 3 figures, 4 tables.

  19. Pharmacogenetics in Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Cheok, Meyling H.; Pottier, Nicolas; Kager, Leo

    2009-01-01

    Progress in the treatment of acute leukemia in children has been remarkable, from a disease being lethal four decades ago to current cure rates exceeding 80%. This exemplary progress is largely due to the optimization of existing treatment modalities rather than the discovery of new antileukemic agents. However, despite these high cure rates, the annual number of children whose leukemia relapses after their initial therapy remains greater than that of new cases of most types of childhood cancers. The aim of pharmacogenetics is to develop strategies to personalize treatment and tailor therapy to individual patients, with the goal of optimizing efficacy and safety through better understanding of human genome variability and its influence on drug response. In this review, we summarize recent pharmacogenomic studies related to the treatment of pediatric acute lymphoblastic leukemia. These studies illustrate the promise of pharmacogenomics to further advance the treatment of human cancers, with childhood leukemia serving as a paradigm. PMID:19100367

  20. Leukemia in children and youths of the Azuay province, Ecuador: 2000-2010.

    Science.gov (United States)

    Zucca, Mariagrazia; Ugalde, Jorge; Arteaga, Francisco Salgado; Biggio, Giuseppe; Flore, Valeria; Nonne, Tinucia; Satta, Giannina; Blangiardo, Marta; Cocco, Pierluigi; Ennas, Maria Grazia

    2013-01-01

    We mapped leukemia risk among children and youths in the Azuay province, Rio Paute river basin, Ecuador, in 2000-2010, using a Bayesian disease mapping model. We assessed the comprehensiveness of the list of leukemia cases from the Sociedad de Lucha contra el Càncer en el Ecuador (SOLCA) Hospital in Cuenca, the only referral center for oncology in the whole Rio Paute area, by comparison to the Quito cancer registry. Risk of leukemia did not vary significantly by canton within the Azuay province. However, a moderate increase in risk of borderline statistical significance was observed in the city of Cuenca and particularly among males in a heavily industrialized parish, who had an almost eight-fold excess (95% CI 3.03, 20.39, p = 0.01) of AML. Analytical studies are warranted to properly address specific etiological factor of leukemia among children and youths of the Azuay province of Ecuador.

  1. A case of acute lymphoblastic leukemia with abnormal brain CT scan after cranial irradiation for central nervous system leukemia

    International Nuclear Information System (INIS)

    Sato, Junko; Abe, Takanori; Watanabe, Tsutomu

    1988-01-01

    A 21-year-old woman with acute lymphoblastic leukemia presented with central neurologic symptoms immediately after the second irradiation (20 Gy to the brain and 10 Gy to the spinal cord) for central nervous system (CNS)-leukemia 3 years and 2 months after the first cranial irradiation with 20 Gy. White matter was depicted as diffusely high density area on CT; histology revealed necrosis of leukemic cells. In the present patient with repeated recurrent CNS-leukemia, leukemic cells seemed to have been damaged simultaneously after irradiation because of parenchymal widespread involvement of leukemic cells, resulting in brain edema, an increased intracranial pressure and parenchymal disturbance. This finding may have an important implication for the risk of cranial irradiation in the case of widespread involvement of leukemic cells. Re-evaluation of cranial irradiation in such cases is suggested. (Namekawa, K.)

  2. Acute myeloid leukemia in children: Current status and future directions.

    Science.gov (United States)

    Taga, Takashi; Tomizawa, Daisuke; Takahashi, Hiroyuki; Adachi, Souichi

    2016-02-01

    Acute myeloid leukemia (AML) accounts for 25% of pediatric leukemia and affects approximately 180 patients annually in Japan. The treatment outcome for pediatric AML has improved through advances in chemotherapy, hematopoietic stem cell transplantation (HSCT), supportive care, and optimal risk stratification. Currently, clinical pediatric AML studies are conducted separately according to the AML subtypes: de novo AML, acute promyelocytic leukemia (APL), and myeloid leukemia with Down syndrome (ML-DS). Children with de novo AML are treated mainly with anthracyclines and cytarabine, in some cases with HSCT, and the overall survival (OS) rate now approaches 70%. Children with APL are treated with an all-trans retinoic acid (ATRA)-combined regimen with an 80-90% OS. Children with ML-DS are treated with a less intensive regimen compared with non-DS patients, and the OS is approximately 80%. HSCT in first remission is restricted to children with high-risk de novo AML only. To further improve outcomes, it will be necessary to combine more accurate risk stratification strategies using molecular genetic analysis with assessment of minimum residual disease, and the introduction of new drugs in international collaborative clinical trials. © 2015 Japan Pediatric Society.

  3. PROGRESS IN ACUTE MYELOID LEUKEMIA

    Science.gov (United States)

    Kadia, Tapan M.; Ravandi, Farhad; O’Brien, Susan; Cortes, Jorge; Kantarjian, Hagop M.

    2014-01-01

    Significant progress has been made in the treatment of acute myeloid leukemia (AML). Steady gains in clinical research and a renaissance of genomics in leukemia have led to improved outcomes. The recognition of tremendous heterogeneity in AML has allowed individualized treatments of specific disease entities within the context of patient age, cytogenetics, and mutational analysis. The following is a comprehensive review of the current state of AML therapy and a roadmap of our approach to these distinct disease entities. PMID:25441110

  4. Plasma cell leukemia

    DEFF Research Database (Denmark)

    Fernández de Larrea, C; Kyle, R A; Durie, B G M

    2013-01-01

    Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic......-pathological entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (≥ 20%) and absolute number (≥ 2 × 10(9)/l) of plasma cells in the peripheral blood. It is proposed that the thresholds...... regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem cell transplantation if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding...

  5. Treatment of prolymphocytic leukemia

    International Nuclear Information System (INIS)

    Hollister, D. Jr.; Coleman, M.

    1982-01-01

    Prolymphocytic leukemia is characterized by marked splenomegaly, distinctive cellular morphologic characteristics, and a poor clinical course. Five patients with typical PL were treated systematically with vincristine/prednisone, chlorambucil/prednisone, splenic irradiation, splenectomy, and other chemotherapy regimens. No patient responded to vincristine/prednisone. Two patients responded to chlorambucil/prednisone, and four patients had brief responses to splenic irradiation. Two patients underwent splenectomy, one of whom had a prolonged clinical remission. There were no complete remissions. No other chemotherapy combinations were of value. The median survival was 33 months. Recommendations are made to use chlorambucil/prednisone or splenic irradiation as initial treatment. Splenectomy should be considered in patients refractory to these modalities. The course of PL may be more protracted than originally reported

  6. Treatment of prolymphocytic leukemia

    International Nuclear Information System (INIS)

    Hollister, S. Jr.; Coleman, M.

    1982-01-01

    Prolymphocytic leukemia is characterized by marked splenomegaly, distinctive cellular morphologic characteristics, and a poor clinical course. Five patients with typical PL were treated systematically with vincristine/prednisone, chlorambucil/prednisone, splenic irradiation, splenectomy, and other chemotherapy regimens. No patient responded to vincristine/prednisone. Two patients responded to chlorambucil/prednisone, and four patients had brief responses to splenic irradiation. Two patients underwent splenectomy, one of whom had a prolonged clinical remissions. No other chemotherapy combinations were of value. The median survival was 33 months. Recommendations are made to use chlorambucil/prednisone or splenic irradiation as initial treatment. Splenectomy should be considered in patients refractory to these modalities. The course of PL may be more protracted than originally reported

  7. EVALUATING RISK-PREDICTION MODELS USING DATA FROM ELECTRONIC HEALTH RECORDS.

    Science.gov (United States)

    Wang, L E; Shaw, Pamela A; Mathelier, Hansie M; Kimmel, Stephen E; French, Benjamin

    2016-03-01

    The availability of data from electronic health records facilitates the development and evaluation of risk-prediction models, but estimation of prediction accuracy could be limited by outcome misclassification, which can arise if events are not captured. We evaluate the robustness of prediction accuracy summaries, obtained from receiver operating characteristic curves and risk-reclassification methods, if events are not captured (i.e., "false negatives"). We derive estimators for sensitivity and specificity if misclassification is independent of marker values. In simulation studies, we quantify the potential for bias in prediction accuracy summaries if misclassification depends on marker values. We compare the accuracy of alternative prognostic models for 30-day all-cause hospital readmission among 4548 patients discharged from the University of Pennsylvania Health System with a primary diagnosis of heart failure. Simulation studies indicate that if misclassification depends on marker values, then the estimated accuracy improvement is also biased, but the direction of the bias depends on the direction of the association between markers and the probability of misclassification. In our application, 29% of the 1143 readmitted patients were readmitted to a hospital elsewhere in Pennsylvania, which reduced prediction accuracy. Outcome misclassification can result in erroneous conclusions regarding the accuracy of risk-prediction models.

  8. Tempo in electronic gaming machines affects behavior among at-risk gamblers.

    Science.gov (United States)

    Mentzoni, Rune A; Laberg, Jon Christian; Brunborg, Geir Scott; Molde, Helge; Pallesen, Ståle

    2012-09-01

    Background and aims Electronic gaming machines (EGM) may be a particularly addictive form of gambling, and gambling speed is believed to contribute to the addictive potential of such machines. The aim of the current study was to generate more knowledge concerning speed as a structural characteristic in gambling, by comparing the effects of three different bet-to-outcome intervals (BOI) on gamblers bet-sizes, game evaluations and illusion of control during gambling on a computer simulated slot machine. Furthermore, we investigated whether problem gambling moderates effects of BOI on gambling behavior and cognitions. Methods 62 participants played a computerized slot machine with either fast (400 ms), medium (1700 ms) or slow (3000 ms) BOI. SOGS-R was used to measure pre-existing gambling problems. Mean bet size, game evaluations and illusion of control comprised the dependent variables. Results Gambling speed had no overall effect on either mean bet size, game evaluations or illusion of control, but in the 400 ms condition, at-risk gamblers (SOGS-R score > 0) employed higher bet sizes compared to no-risk (SOGS-R score = 0) gamblers. Conclusions The findings corroborate and elaborate on previous studies and indicate that restrictions on gambling speed may serve as a harm reducing effort for at-risk gamblers.

  9. Electronics

    Science.gov (United States)

    2001-01-01

    International Acer Incorporated, Hsin Chu, Taiwan Aerospace Industrial Development Corporation, Taichung, Taiwan American Institute of Taiwan, Taipei, Taiwan...Singapore and Malaysia .5 - 4 - The largest market for semiconductor products is the high technology consumer electronics industry that consumes up...Singapore, and Malaysia . A new semiconductor facility costs around $3 billion to build and takes about two years to become operational

  10. Individualized toxicity-titrated 6-mercaptopurine increments during high-dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Frandsen, Thomas Leth; Abrahamsson, Jonas; Lausen, Birgitte Frederiksen

    2011-01-01

    This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m2, ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m2 per...... the remaining patients (P = 0·03). This study shows individualized toxicity-titrated 6MP dosing during consolidation is feasible without increased risk of toxicity....

  11. Prospective, longitudinal assessment of quality of life in children from diagnosis to 3 months off treatment for standard risk acute lymphoblastic leukemia: Results of Children's Oncology Group study AALL0331.

    Science.gov (United States)

    Mitchell, Hannah-Rose; Lu, Xiaomin; Myers, Regina M; Sung, Lillian; Balsamo, Lyn M; Carroll, William L; Raetz, Elizabeth; Loh, Mignon L; Mattano, Leonard A; Winick, Naomi J; Devidas, Meenakshi; Hunger, Stephen P; Maloney, Kelly; Kadan-Lottick, Nina S

    2016-01-15

    Standard risk acute lymphoblastic leukemia (SR-ALL) has high cure rates, but requires 2-3 years of therapy. We aimed to (i) prospectively evaluate health-related quality of life (HRQOL) during and after SR-ALL therapy, and (ii) identify associated predictors. Parents of 160 SR-ALL patients enrolled on Children's Oncology Group (COG) therapeutic trial AALL0331 at 31 sites completed the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales (physical, emotional and social functioning) and Family Assessment Device-General Functioning (FAD-GF) at 1, 6 and 12 months after diagnosis, and 3 months post-therapy. Mean PedsQL scores in physical, emotional and social functioning were impaired 1 month after diagnosis but steadily improved. Three months post-therapy, impaired physical and social functioning was observed in 27.8 and 25.8% of patients, respectively. In repeated-measures analysis, problematic family functioning predicted emotional (OR = 1.85, 95% CI 1.03-3.34) and social (OR = 1.99, 95% CI 1.21-3.27) impairment. Larger household size was associated with social impairment (OR = 1.21, 95% CI 1.02-1.45). Adverse neurological event(s) during therapy predicted post-therapy physical (OR = 5.17, 95% CI 1.61-16.63) and social (OR = 8.17, 95% CI 1.19-56.16) impairment. HRQOL 1 month after diagnosis was not predictive of HRQOL 3 months after therapy completion. In conclusion, children with SR-ALL experience considerable impairment in HRQOL at the end of induction, but rapidly improve. However, many still experience physical and social impairment 3 months post-therapy, suggesting a role for continued family and physical functioning support. Longer follow-up is needed to determine if post-therapy deficits change over time. © 2015 UICC.

  12. Management of chronic lymphocytic leukemia.

    Science.gov (United States)

    Stilgenbauer, Stephan; Furman, Richard R; Zent, Clive S

    2015-01-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is usually diagnosed in asymptomatic patients with early-stage disease. The standard management approach is careful observation, irrespective of risk factors unless patients meet the International Workshop on CLL (IWCLL) criteria for "active disease," which requires treatment. The initial standard therapy for most patients combines an anti-CD20 antibody (such as rituximab, ofatumumab, or obinutuzumab) with chemotherapy (fludarabine/cyclophosphamide [FC], bendamustine, or chlorambucil) depending on multiple factors including the physical fitness of the patient. However, patients with very high-risk CLL because of a 17p13 deletion (17p-) with or without mutation of TP53 (17p-/TP53mut) have poor responses to chemoimmunotherapy and require alternative treatment regimens containing B-cell receptor (BCR) signaling pathway inhibitors. The BCR signaling pathway inhibitors (ibrutinib targeting Bruton's tyrosine kinase [BTK] and idelalisib targeting phosphatidyl-inositol 3-kinase delta [PI3K-delta], respectively) are currently approved for the treatment of relapsed/refractory CLL and all patients with 17p- (ibrutinib), and in combination with rituximab for relapsed/refractory patients (idelalisib). These agents offer great efficacy, even in chemotherapy refractory CLL, with increased tolerability, safety, and survival. Ongoing studies aim to determine the best therapy combinations with the goal of achieving long-term disease control and the possibility of developing a curative regimen for some patients. CLL is associated with a wide range of infectious, autoimmune, and malignant complications. These complications result in considerable morbidity and mortality that can be minimized by early detection and aggressive management. This active monitoring requires ongoing patient education, provider vigilance, and a team approach to patient care.

  13. Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial.

    Science.gov (United States)

    Platzbecker, Uwe; Avvisati, Giuseppe; Cicconi, Laura; Thiede, Christian; Paoloni, Francesca; Vignetti, Marco; Ferrara, Felicetto; Divona, Mariadomenica; Albano, Francesco; Efficace, Fabio; Fazi, Paola; Sborgia, Marco; Di Bona, Eros; Breccia, Massimo; Borlenghi, Erika; Cairoli, Roberto; Rambaldi, Alessandro; Melillo, Lorella; La Nasa, Giorgio; Fiedler, Walter; Brossart, Peter; Hertenstein, Bernd; Salih, Helmut R; Wattad, Mohammed; Lübbert, Michael; Brandts, Christian H; Hänel, Mathias; Röllig, Christoph; Schmitz, Norbert; Link, Hartmut; Frairia, Chiara; Pogliani, Enrico Maria; Fozza, Claudio; D'Arco, Alfonso Maria; Di Renzo, Nicola; Cortelezzi, Agostino; Fabbiano, Francesco; Döhner, Konstanze; Ganser, Arnold; Döhner, Hartmut; Amadori, Sergio; Mandelli, Franco; Ehninger, Gerhard; Schlenk, Richard F; Lo-Coco, Francesco

    2017-02-20

    Purpose The initial results of the APL0406 trial showed that the combination of all- trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial. Eligible patients were adults between 18 and 71 years of age with newly diagnosed, low- or intermediate-risk APL (WBC at diagnosis ≤ 10 × 10 9 /L). Overall, 276 patients were randomly assigned to receive ATRA-ATO or ATRA-CHT between October 2007 and January 2013. Results Of 263 patients evaluable for response to induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients achieved complete remission (CR) in the ATRA-ATO and ATRA-CHT arms, respectively ( P = .12). After a median follow-up of 40.6 months, the event-free survival, cumulative incidence of relapse, and overall survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms were 97.3% v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively ( P < .001, P = .0013, and P = .0073, respectively). Postinduction events included two relapses and one death in CR in the ATRA-ATO arm and two instances of molecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm. Two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm. Conclusion These results show that the advantages of ATRA-ATO over ATRA-CHT increase over time and that there is significantly greater and more sustained antileukemic efficacy of ATO-ATRA compared with ATRA-CHT in low- and intermediate-risk APL.

  14. Seroprevalences of feline leukemia virus and feline immunodeficiency virus infection in cats in the United States and Canada and risk factors for seropositivity.

    Science.gov (United States)

    Burling, Amie N; Levy, Julie K; Scott, H Morgan; Crandall, Michael M; Tucker, Sylvia J; Wood, Erin G; Foster, Jessie D

    2017-07-15

    OBJECTIVE To estimate seroprevalences for FeLV antigen and anti-FIV antibody and risk factors for seropositivity among cats in the United States and Canada. DESIGN Cross-sectional study. ANIMALS 62,301 cats tested at 1,396 veterinary clinics (n = 45,406) and 127 animal shelters (16,895). PROCEDURES Blood samples were tested with a point-of-care ELISA for FeLV antigen and anti-FIV antibody. Seroprevalence was estimated, and risk factors for seropositivity were evaluated with bivariate and multivariable mixed-model logistic regression analyses adjusted for within-clinic or within-shelter dependencies. RESULTS Overall, seroprevalence was 3.1% for FeLV antigen and 3.6% for anti-FIV antibody. Adult age, outdoor access, clinical disease, and being a sexually intact male were risk factors for seropositivity for each virus. Odds of seropositivity for each virus were greater for cats tested in clinics than for those tested in shelters. Of 1,611 cats with oral disease, 76 (4.7%) and 157 (9.7%) were seropositive for FeLV and FIV, respectively. Of 4,835 cats with respiratory disease, 385 (8.0%) were seropositive for FeLV and 308 (6.4%) were seropositive for FIV. Of 1,983 cats with abscesses or bite wounds, 110 (5.5%) and 247 (12.5%) were seropositive for FeLV and FIV, respectively. Overall, 2,368 of 17,041 (13.9%) unhealthy cats were seropositive for either or both viruses, compared with 1,621 of 45,260 (3.6%) healthy cats. CONCLUSIONS AND CLINICAL RELEVANCE Seroprevalences for FeLV antigen and anti-FIV antibody were similar to those reported in previous studies over the past decade. Taken together, these results indicated a need to improve compliance with existing guidelines for management of feline retroviruses.

  15. ALLOGENEIC TRANSPLANTATION FOR CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Luca Laurenti

    2010-08-01

    Full Text Available Even if Chronic lymphocytic leukemia (CLL often has an indolent behavior with good responsiveness to cytoreductive treatment, about 20% of the patients, so called "poor-risk" patients, show an aggressive course and die within a few years despite early intensive therapies. Criteria for poor-risk disease according to the European Bone Marrow Transplantation (EBMT CLL Transplant Consensus are: purine analogue refractoriness, early relapse after purine analogue combination therapy, CLL with p53 lesion requiring treatment. Allogeneic transplant has potential curative role in CLL, however burden with very  high transplant related mortality (TRM rates of 38-50%: A major advance in reducing the short-term morbidity and mortality of allogeneic stem cell transplantation (SCT has been the introduction of non-myeloablative or reduced intensity conditioning (RIC regimens to allow engraftment of allogeneic stem cells. There is no doubt that the crucial therapeutic principle of allo-SCT in CLL is graft versus leukemia (GVL activity. The major complications of allogeneic SCT in CLL are: chronic graft-versus-host-disease (GVHD affecting quality of life, high graft rejection and infection rates rates correlated with preexisting immunosuppression. Disease relapse remains the major cause of failure after RIC allo-HCT in CLL patients. Sensitive minimal residual disease (MRD quantification has strong prognostic impact after transplant.

  16. Ref-1/APE1 as a Transcriptional Regulator and Novel Therapeutic Target in Pediatric T-cell Leukemia.

    Science.gov (United States)

    Ding, Jixin; Fishel, Melissa L; Reed, April M; McAdams, Erin; Czader, Magdalena B; Cardoso, Angelo A; Kelley, Mark R

    2017-07-01

    The increasing characterization of childhood acute lymphoblastic leukemia (ALL) has led to the identification of multiple molecular targets but has yet to translate into more effective targeted therapies, particularly for high-risk, relapsed T-cell ALL. Searching for master regulators controlling multiple signaling pathways in T-ALL, we investigated the multifunctional protein redox factor-1 (Ref-1/APE1), which acts as a signaling "node" by exerting redox regulatory control of transcription factors important in leukemia. Leukemia patients' transcriptome databases showed increased expression in T-ALL of Ref-1 and other genes of the Ref-1/SET interactome. Validation studies demonstrated that Ref-1 is expressed in high-risk leukemia T cells, including in patient biopsies. Ref-1 redox function is active in leukemia T cells, regulating the Ref-1 target NF-κB, and inhibited by the redox-selective Ref-1 inhibitor E3330. Ref-1 expression is not regulated by Notch signaling, but is upregulated by glucocorticoid treatment. E3330 disrupted Ref-1 redox activity in functional studies and resulted in marked inhibition of leukemia cell viability, including T-ALL lines representing different genotypes and risk groups. Potent leukemia cell inhibition was seen in primary cells from ALL patients, relapsed and glucocorticoid-resistant T-ALL cells, and cells from a murine model of Notch-induced leukemia. Ref-1 redox inhibition triggered leukemia cell apoptosis and downregulation of survival genes regulated by Ref-1 targets. For the first time, this work identifies Ref-1 as a novel molecular effector in T-ALL and demonstrates that Ref-1 redox inhibition results in potent inhibition of leukemia T cells, including relapsed T-ALL. These data also support E3330 as a specific Ref-1 small-molecule inhibitor for leukemia. Mol Cancer Ther; 16(7); 1401-11. ©2017 AACR . ©2017 American Association for Cancer Research.

  17. Nighttime exposure to electromagnetic fields and childhood leukemia: an extended pooled analysis

    DEFF Research Database (Denmark)

    Schüz, Joachim; Svendsen, Anne Louise; Linet, Martha S

    2007-01-01

    analysis of case-control studies on ELF EMF exposure and risk of childhood leukemia to examine nighttime residential exposures. Data from four countries (Canada, Germany, the United Kingdom, and the United States) were included in the analysis, comprising 1,842 children diagnosed with leukemia and 3......,099 controls (diagnosis dates ranged from 1988 to 1996). The odds ratios for nighttime ELF EMF exposure for categories of 0.1-or=0.4 microT as compared with ... that nighttime measures are more appropriate; hence, the observed association between ELF EMF and childhood leukemia still lacks a plausible explanation....

  18. Acute Lymphoblastic Leukemia in a Man Treated With Fingolimod for Relapsing Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Stanley Cohan MD, PhD

    2015-03-01

    Full Text Available A man with relapsing multiple sclerosis, treated with fingolimod 0.5 mg/d for 15 months, developed acute lymphoblastic leukemia and died 4 months after immune ablation and bone marrow allograft, from graft versus host disease. To our knowledge, this is the first case of acute lymphoblastic leukemia reported in a patient treated with fingolimod. Although no causal relationship can be established between fingolimod use and acute lymphoblastic leukemia risk in this single case, future surveillance for lymphatic cell malignancies in patients treated with fingolimod appears justified.

  19. Quantitation of human thymus/leukemia-associated antigen by radioimmunoassay in different forms of leukemia.

    Science.gov (United States)

    Chechik, B E; Jason, J; Shore, A; Baker, M; Dosch, H M; Gelfand, E W

    1979-12-01

    Using a radioimmunoassay, increased levels of a human thymus/leukemia-associated antigen (HThy-L) have been detected in leukemic cells and plasma from most patients with E-rosette-positive acute lymphoblastic leukemia (ALL) and a number of patients with E-rosette-negative ALL, acute myeloblastic leukemia (AML), acute monomyelocytic leukemia (AMML), and acute undifferentiated leukemia (AVL). Low levels of HThy-L have been demonstrated in white cells from patients with chronic myelocytic leukemia (stable phase) and in mononuclear cells from patients with chronic lymphatic leukemia. The relationship between HThy-L and differentiation of hematopoietic cells is discussed.

  20. Treatment Option Overview (Chronic Myelogenous Leukemia)

    Science.gov (United States)

    ... ALL Treatment Childhood AML Treatment Research Chronic Myelogenous Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Myelogenous Leukemia Go to Health Professional Version Key Points Chronic ...

  1. General Information about Chronic Myelogenous Leukemia

    Science.gov (United States)

    ... ALL Treatment Childhood AML Treatment Research Chronic Myelogenous Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Myelogenous Leukemia Go to Health Professional Version Key Points Chronic ...

  2. Mercaptopurine Ingestion Habits, Red Cell Thioguanine Nucleotide Levels, and Relapse Risk in Children With Acute Lymphoblastic Leukemia: A Report From the Children’s Oncology Group Study AALL03N1

    Science.gov (United States)

    Landier, Wendy; Hageman, Lindsey; Chen, Yanjun; Kornegay, Nancy; Evans, William E.; Bostrom, Bruce C.; Casillas, Jacqueline; Dickens, David S.; Angiolillo, Anne L.; Lew, Glen; Maloney, Kelly W.; Mascarenhas, Leo; Ritchey, A. Kim; Termuhlen, Amanda M.; Carroll, William L.; Relling, Mary V.; Wong, F. Lennie

    2017-01-01

    Purpose Children with acute lymphoblastic leukemia (ALL) are generally instructed to take mercaptopurine (6-MP) in the evening and without food or dairy products. This study examines the association between 6-MP ingestion habits and 6-MP adherence, red cell thioguanine nucleotide (TGN) levels, and risk of relapse in children with TMPT wild-type genotype. Methods Participants included 441 children with ALL receiving oral 6-MP for maintenance. Adherence was monitored over 48,086 patient-days using the Medication Event Monitoring System; nonadherence was defined as adherence rate < 95%. 6-MP ingestion habits examined included: takes 6-MP with versus never with food, takes 6-MP with versus never with dairy, and takes 6-MP in the evening versus morning versus varying times. Results Median age at study was 6 years (range, 2 to 20 years); 43.8% were nonadherent. Certain 6-MP ingestion habits were associated with nonadherence (taking 6-MP with dairy [odds ratio (OR), 1.9; 95% CI, 1.3 to 2.9; P = .003] and at varying times [OR, 3.4; 95% CI, 1.8 to 6.3; P = .0001]). After adjusting for adherence and other prognosticators, there was no association between 6-MP ingestion habits and relapse risk (6-MP with food: hazard ratio [HR], 0.7; 95% CI, 0.3 to 1.9; P = .5; with dairy: HR, 0.3; 95% CI, 0.07 to 1.5; P = .2; taken in evening/night: HR, 1.1; 95% CI, 0.2 to 7.8; P = .9; at varying times: HR, 0.3; 95% CI, 0.04 to 2.7; P = .3). Among adherent patients, there was no association between red cell TGN levels and taking 6-MP with food versus without (206.1 ± 107.1 v 220.6 ± 121.6; P = .5), with dairy versus without (220.1 ± 87.8 v 216.3 ± 121.3; P =.7), or in the evening/night versus morning/midday versus varying times (218.8 ± 119.7 v 195.5 ± 82.3 v 174.8 ± 93.4; P = .6). Conclusion Commonly practiced restrictions surrounding 6-MP ingestion might not influence outcome but may hinder adherence. Future recommendations regarding 6-MP intake during maintenance therapy for

  3. Mercaptopurine Ingestion Habits, Red Cell Thioguanine Nucleotide Levels, and Relapse Risk in Children With Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group Study AALL03N1.

    Science.gov (United States)

    Landier, Wendy; Hageman, Lindsey; Chen, Yanjun; Kornegay, Nancy; Evans, William E; Bostrom, Bruce C; Casillas, Jacqueline; Dickens, David S; Angiolillo, Anne L; Lew, Glen; Maloney, Kelly W; Mascarenhas, Leo; Ritchey, A Kim; Termuhlen, Amanda M; Carroll, William L; Relling, Mary V; Wong, F Lennie; Bhatia, Smita

    2017-05-20

    Purpose Children with acute lymphoblastic leukemia (ALL) are generally instructed to take mercaptopurine (6-MP) in the evening and without food or dairy products. This study examines the association between 6-MP ingestion habits and 6-MP adherence, red cell thioguanine nucleotide (TGN) levels, and risk of relapse in children with TMPT wild-type genotype. Methods Participants included 441 children with ALL receiving oral 6-MP for maintenance. Adherence was monitored over 48,086 patient-days using the Medication Event Monitoring System; nonadherence was defined as adherence rate < 95%. 6-MP ingestion habits examined included: takes 6-MP with versus never with food, takes 6-MP with versus never with dairy, and takes 6-MP in the evening versus morning versus varying times. Results Median age at study was 6 years (range, 2 to 20 years); 43.8% were nonadherent. Certain 6-MP ingestion habits were associated with nonadherence (taking 6-MP with dairy [odds ratio (OR), 1.9; 95% CI, 1.3 to 2.9; P = .003] and at varying times [OR, 3.4; 95% CI, 1.8 to 6.3; P = .0001]). After adjusting for adherence and other prognosticators, there was no association between 6-MP ingestion habits and relapse risk (6-MP with food: hazard ratio [HR], 0.7; 95% CI, 0.3 to 1.9; P = .5; with dairy: HR, 0.3; 95% CI, 0.07 to 1.5; P = .2; taken in evening/night: HR, 1.1; 95% CI, 0.2 to 7.8; P = .9; at varying times: HR, 0.3; 95% CI, 0.04 to 2.7; P = .3). Among adherent patients, there was no association between red cell TGN levels and taking 6-MP with food versus without (206.1 ± 107.1 v 220.6 ± 121.6; P = .5), with dairy versus without (220.1 ± 87.8 v 216.3 ± 121.3; P =.7), or in the evening/night versus morning/midday versus varying times (218.8 ± 119.7 v 195.5 ± 82.3 v 174.8 ± 93.4; P = .6). Conclusion Commonly practiced restrictions surrounding 6-MP ingestion might not influence outcome but may hinder adherence. Future recommendations regarding 6-MP intake during maintenance therapy for

  4. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... cells in the blood at the time of diagnosis. Whether the leukemia cells began from B lymphocytes or T lymphocytes. ... How long it is between the time of diagnosis and when the leukemia comes back. Whether the leukemia comes back in ...

  5. General Information about Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... cells in the blood at the time of diagnosis. Whether the leukemia cells began from B lymphocytes or T lymphocytes. ... How long it is between the time of diagnosis and when the leukemia comes back. Whether the leukemia comes back in ...

  6. Monoclonal antibodies reactive with hairy cell leukemia

    NARCIS (Netherlands)

    Visser, L; Shaw, A; Slupsky, J; Vos, H; Poppema, S

    Monoclonal antibodies reactive with hairy cell leukemia were developed to aid in the diagnosis of this subtype of B cell chronic lymphocytic leukemia and to gain better insight into the origin of hairy cells. Three antibodies were found to be of value in the diagnosis of hairy cell leukemia.

  7. Work-related musculoskeletal disorders (WMDs) risk assessment at core assembly production of electronic components manufacturing company

    Science.gov (United States)

    Yahya, N. M.; Zahid, M. N. O.

    2018-03-01

    This study conducted to assess the work-related musculoskeletal disorders (WMDs) among the workers at core assembly production in an electronic components manufacturing company located in Pekan, Pahang, Malaysia. The study is to identify the WMDs risk factor and risk level. A set of questionnaires survey based on modified Nordic Musculoskeletal Disorder Questionnaires have been distributed to respective workers to acquire the WMDs risk factor identification. Then, postural analysis was conducted in order to measure the respective WMDs risk level. The analysis were based on two ergonomics assessment tools; Rapid Upper Limb Assessment (RULA) and Rapid Entire Body Assessment (REBA). The study found that 30 respondents out of 36 respondents suffered from WMDs especially at shoulder, wrists and lower back. The WMDs risk have been identified from unloading process, pressing process and winding process. In term of the WMDs risk level, REBA and RULA assessment tools have indicated high risk level to unloading and pressing process. Thus, this study had established the WMDs risk factor and risk level of core assembly production in an electronic components manufacturing company at Malaysia environment.

  8. Acute leukemias of ambiguous lineage.

    Science.gov (United States)

    Béné, Marie C; Porwit, Anna

    2012-02-01

    The 2008 edition of the WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues recognizes a special category called "leukemias of ambiguous lineage." The vast majority of these rare leukemias are classified as mixed phenotype acute leukemia (MPAL), although acute undifferentiated leukemias and natural killer lymphoblastic leukemias are also included. The major immunophenotypic markers used by the WHO 2008 to determine the lineage for these proliferations are myeloperoxidase, CD19, and cytoplasmic CD3. However, extensive immunophenotyping is necessary to confirm that the cells indeed belong to 2 different lineages or coexpress differentiation antigens of more than 1 lineage. Specific subsets of MPAL are defined by chromosomal anomalies such as the t(9;22) Philadelphia chromosome BCR-ABL1 or involvement of the MLL gene on chromosome 11q23. Other MPAL are divided into B/myeloid NOS, T/myeloid NOS, B/T NOS, and B/T/myeloid NOS. MPAL are usually of dire prognosis, respond variably to chemotherapy of acute lymphoblastic or acute myeloblastic type, and benefit most from rapid allogeneic hematopoietic stem cell transplantation.

  9. Fanconi anemia and the development of leukemia.

    Science.gov (United States)

    Alter, Blanche P

    2014-01-01

    Fanconi anemia (FA) is a rare autosomal recessive cancer-prone inherited bone marrow failure syndrome, due to mutations in 16 genes, whose protein products collaborate in a DNA repair pathway. The major complications are aplastic anemia, acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and specific solid tumors. A severe subset, due to mutations in FANCD1/BRCA2, has a cumulative incidence of cancer of 97% by age 7 years; the cancers are AML, brain tumors, and Wilms tumor; several patients have multiple events. Patients with the other genotypes (FANCA through FANCQ) have cumulative risks of more than 50% of marrow failure, 20% of AML, and 30% of solid tumors (usually head and neck or gynecologic squamous cell carcinoma), by age 40, and they too are at risk of multiple adverse events. Hematopoietic stem cell transplant may cure AML and MDS, and preemptive transplant may be appropriate, but its use is a complicated decision. Published by Elsevier Ltd.

  10. Mosaic Down syndrome and acute lymphoblastic B cell-leukemia. Case report

    Directory of Open Access Journals (Sweden)

    Parra-Baltazar, Isabel Mónica

    2016-10-01

    Full Text Available Down syndrome (DS or trisomy 21 is a constitutional chromosomal abnormality, which may be mosaic in 1 % to 4 % of cases. DS mosaic diagnosis is difficult because most patients have a normal phenotype and show no significant clinical abnormalities. Patients with DS have a higher risk of developing acute leukemia such as acute lymphoblastic leukemia (ALL. We report the case of a 19-year old woman with mosaic trisomy 21 and ALL.

  11. Secondary Leukemia Associated with the Anti-Cancer Agent, Etoposide, a Topoisomerase II Inhibitor

    OpenAIRE

    Sachiko Ezoe

    2012-01-01

    Etoposide is an anticancer agent, which is successfully and extensively used in treatments for various types of cancers in children and adults. However, due to the increases in survival and overall cure rate of cancer patients, interest has arisen on the potential risk of this agent for therapy-related secondary leukemia. Topoisomerase II inhibitors, including etoposide and teniposide, frequently cause rearrangements involving the mixed lineage leukemia (MLL<...

  12. Parental and infant characteristics and childhood leukemia in Minnesota

    Directory of Open Access Journals (Sweden)

    Ross Julie A

    2008-02-01

    Full Text Available Abstract Background Leukemia is the most common childhood cancer. With the exception of Down syndrome, prenatal radiation exposure, and higher birth weight, particularly for acute lymphoid leukemia (ALL, few risk factors have been firmly established. Translocations present in neonatal blood spots and the young age peak of diagnosis suggest that early-life factors are involved in childhood leukemia etiology. Methods We investigated the association between birth characteristics and childhood leukemia through linkage of the Minnesota birth and cancer registries using a case-cohort study design. Cases included 560 children with ALL and 87 with acute myeloid leukemia (AML diagnoses from 28 days to 14 years. The comparison group was comprised of 8,750 individuals selected through random sampling of the birth cohort from 1976–2004. Cox proportional hazards regression specific for case-cohort studies was used to compute hazard ratios (HR and 95% confidence intervals (CIs. Results Male sex (HR = 1.41, 95% CI 1.16–1.70, white race (HR = 2.32, 95% CI 1.13–4.76, and maternal birth interval ≥ 3 years (HR = 1.31, 95% CI 1.01–1.70 increased ALL risk, while maternal age increased AML risk (HR = 1.21/5 year age increase, 95% CI 1.0–1.47. Higher birth weights (>3798 grams (HRALL = 1.46, 1.08–1.98; HRAML = 1.97, 95% CI 1.07–3.65, and one minute Apgar scores ≤ 7 (HRALL = 1.30, 95% CI 1.05–1.61; HRAML = 1.62, 95% CI 1.01–2.60 increased risk for both types of leukemia. Sex was not a significant modifier of the association between ALL and other covariates, with the exception of maternal education. Conclusion We confirmed known risk factors for ALL: male sex, high birth weight, and white race. We have also provided data that supports an increased risk for AML following higher birth weights, and demonstrated an association with low Apgar scores.

  13. High concordance of subtypes of childhood acute lymphoblastic leukemia within families

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Thomsen, U Lautsen; Baruchel, A

    2012-01-01

    Polymorphic genes have been linked to the risk of acute lymphoblastic leukemia (ALL). Surrogate markers for a low burden of early childhood infections are also related to increased risk for developing childhood ALL. It remains uncertain, whether siblings of children with ALL have an increased risk...

  14. Childhood leukemia around nuclear facilities

    International Nuclear Information System (INIS)

    1991-01-01

    This Information Bulletin highlights the conclusion made from an Atomic Energy Control Board of Canada (AECB) study on the incidence of childhood leukemia near nuclear facilities. All of the locations with the nuclear facilities are located in Ontario, the nuclear generating stations at Pickering and Bruce; the uranium mines and mills in Elliot Lake; the uranium refining facility in Port Hope; and nuclear research facilities located at Chalk River plus the small nuclear power plant in Rolphton. Two conclusions are drawn from the study: 1) while the rate of childhood leukemias made be higher or lower than the provincial average, there is no statistical evidence that the difference is due to anything but the natural variation in the occurrence of the disease; and 2) the rate of occurrence of childhood leukemia around the Pickering nuclear power station was slightly greater than the Ontario average both before and after the plant opened, but this, too , could be due to the natural variation

  15. Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers Differentiation Block in Acute Leukemia

    Directory of Open Access Journals (Sweden)

    Tim D.D. Somerville

    2018-01-01

    Full Text Available The Iroquois homeodomain transcription factor gene IRX3 is expressed in the developing nervous system, limb buds, and heart, and transcript levels specify obesity risk in humans. We now report a functional role for IRX3 in human acute leukemia. Although transcript levels are very low in normal human bone marrow cells, high IRX3 expression is found in ∼30% of patients with acute myeloid leukemia (AML, ∼50% with T-acute lymphoblastic leukemia, and ∼20% with B-acute lymphoblastic leukemia, frequently in association with high-level HOXA gene expression. Expression of IRX3 alone was sufficient to immortalize hematopoietic stem and progenitor cells (HSPCs in myeloid culture and induce lymphoid leukemias in vivo. IRX3 knockdown induced terminal differentiation of AML cells. Combined IRX3 and Hoxa9 expression in murine HSPCs impeded normal T-progenitor differentiation in lymphoid culture and substantially enhanced the morphologic and phenotypic differentiation block of AML in myeloid leukemia transplantation experiments through suppression of a terminal myelomonocytic program. Likewise, in cases of primary human AML, high IRX3 expression is strongly associated with reduced myelomonocytic differentiation. Thus, tissue-inappropriate derepression of IRX3 contributes significantly to the block in differentiation, which is the pathognomonic feature of human acute leukemias.

  16. Frequency and Reasons for Return to Acute Care in Leukemia Patients Undergoing Inpatient Rehabilitation

    Science.gov (United States)

    Fu, Jack Brian; Lee, Jay; Smith, Dennis W.; Bruera, Eduardo

    2012-01-01

    Objective To assess the frequency and reasons for return to the primary acute care service among leukemia patients undergoing inpatient rehabilitation. Design Retrospective study of all patients with leukemia, myelodysplastic syndrome, aplastic anemia, or myelofibrosis admitted to inpatient rehabilitation at a tertiary referral-based cancer center between January 1, 2005, and April 10, 2012. Items analyzed from patient records included return to the primary acute care service with demographic information, leukemia characteristics, medications, hospital admission characteristics, and laboratory values. Results 225 patients were admitted a total of 255 times. 93/255 (37%) of leukemia inpatient rehabilitation admissions returned to the primary acute care service. 18/93 (19%) and 42/93 (45%) of these patients died in the hospital and were discharged home respectively. Statistically significant factors (p<.05) associated with return to the primary acute care service include peripheral blast percentage and the presence of an antifungal agent on the day of inpatient rehabilitation transfer. Using an additional two factors (platelet count and the presence of an antiviral agent both with a p<.11), a Return To Primary (RTP) - Leukemia index was formulated. Conclusions Leukemia patients with the presence of circulating peripheral blasts and/or antifungal agent may be at increased risk of return to the primary acute care service. The RTP-Leukemia index should be tested in prospective studies to determine its usefulness. PMID:23117267

  17. Secondary Leukemia Associated with the Anti-Cancer Agent, Etoposide, a Topoisomerase II Inhibitor

    Directory of Open Access Journals (Sweden)

    Sachiko Ezoe

    2012-07-01

    Full Text Available Etoposide is an anticancer agent, which is successfully and extensively used in treatments for various types of cancers in children and adults. However, due to the increases in survival and overall cure rate of cancer patients, interest has arisen on the potential risk of this agent for therapy-related secondary leukemia. Topoisomerase II inhibitors, including etoposide and teniposide, frequently cause rearrangements involving the mixed lineage leukemia (MLL gene on chromosome 11q23, which is associated with secondary leukemia. The prognosis is extremely poor for leukemias associated with rearrangements in the MLL gene, including etoposide-related secondary leukemias. It is of great importance to gain precise knowledge of the clinical aspects of these diseases and the mechanism underlying the leukemogenesis induced by this agent to ensure correct assessments of current and future therapy strategies. Here, I will review current knowledge regarding the clinical aspects of etoposide-related secondary leukemia, some probable mechanisms, and strategies for treating etoposide-induced leukemia.

  18. Mass-gathering Medicine: Risks and Patient Presentations at a 2-Day Electronic Dance Music Event.

    Science.gov (United States)

    Lund, Adam; Turris, Sheila A

    2015-06-01

    Music festivals, including electronic dance music events (EDMEs), increasingly are common in Canada and internationally. Part of a US $4.5 billion industry annually, the target audience is youth and young adults aged 15-25 years. Little is known about the impact of these events on local emergency departments (EDs). Drawing on prospective data over a 2-day EDME, the authors of this study employed mixed methods to describe the case mix and prospectively compared patient presentation rate (PPR) and ambulance transfer rate (ATR) between a first aid (FA) only and a higher level of care (HLC) model. There were 20,301 ticketed attendees. Seventy patient encounters were recorded over two days. The average age was 19.1 years. Roughly 69% were female (n=48/70). Forty-six percent of those seen in the main medical area were under the age of 19 years (n=32/70). The average length of stay in the main medical area was 70.8 minutes. The overall PPR was 4.09 per 1,000 attendees. The ATR with FA only would have been 1.98; ATR with HLC model was 0.52. The presence of an on-site HLC team had a significant positive effect on avoiding ambulance transfers. Twenty-nine ambulance transfers and ED visits were avoided by the presence of an on-site HLC medical team. Reduction of impact to the public health care system was substantial. Electronic dance music events have predictable risks and patient presentations, and appropriate on-site health care resources may reduce significantly the impact on the prehospital and emergency health resources in the host community.

  19. Radiological terrorism and estimate leukemia incidence

    Energy Technology Data Exchange (ETDEWEB)

    Saint' Yves, Thalis Leon de Avila [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Instituto Nacional do Cancer (INCa), Rio de Janeiro, RJ (Brazil); Maia, Arlei; Andrade, Edson R. de [Centro Tecnologico do Exercito (CTEX), Rio de Janeiro, RJ (Brazil)

    2011-07-01

    Radiological dispersal devices (RDD) are widely used as a terrorist tool leading to major environmental and public health concerns. This work is focused on simulating a dispersive scenario where an amount of most common radionuclide for this purpose is released. In order to estimate the total effective dose from such release, an affected urban area was chosen as a potential public mass concentration during World Cup in 2014 and Olympics in 2016 in Rio de Janeiro. Specialized simulation software called HotSpot Health Physics Code using a semi-empirical Gaussian model, was used to simulate dispersion of Cs-137 following detonation of a RDD. The simulation was designed to determine dose curves as a function of distance from the hot site. Additionally, it was determined the relative risk of leukemia incidence as well as statistical correlation between malignancies and exposure to radiation, based on probability of causation calculations. Results was suggestive that exists dependence on age at exposure time and the probability of leukemia development. This study emphasizes the importance of fast response, using a user-friendly computational method that may help, at first sight, to guide the response from the basic actions to the complete decision making process looking after health effects on public and environmental detriment. (author)

  20. Radiological terrorism and estimate leukemia incidence

    International Nuclear Information System (INIS)

    Saint'Yves, Thalis Leon de Avila; Maia, Arlei; Andrade, Edson R. de

    2011-01-01

    Radiological dispersal devices (RDD) are widely used as a terrorist tool leading to major environmental and public health concerns. This work is focused on simulating a dispersive scenario where an amount of most common radionuclide for this purpose is released. In order to estimate the total effective dose from such release, an affected urban area was chosen as a potential public mass concentration during World Cup in 2014 and Olympics in 2016 in Rio de Janeiro. Specialized simulation software called HotSpot Health Physics Code using a semi-empirical Gaussian model, was used to simulate dispersion of Cs-137 following detonation of a RDD. The simulation was designed to determine dose curves as a function of distance from the hot site. Additionally, it was determined the relative risk of leukemia incidence as well as statistical correlation between malignancies and exposure to radiation, based on probability of causation calculations. Results was suggestive that exists dependence on age at exposure time and the probability of leukemia development. This study emphasizes the importance of fast response, using a user-friendly computational method that may help, at first sight, to guide the response from the basic actions to the complete decision making process looking after health effects on public and environmental detriment. (author)

  1. Acute leukemia in early childhood

    Directory of Open Access Journals (Sweden)

    M. Emerenciano

    2007-06-01

    Full Text Available Acute leukemia in early childhood is biologically and clinically distinct. The particular characteristics of this malignancy diagnosed during the first months of life have provided remarkable insights into the etiology of the disease. The pro-B, CD10 negative immunophenotype is typically found in infant acute leukemia, and the most common genetic alterations are the rearrangements of the MLL gene. In addition, the TEL/AML1 fusion gene is most frequently found in children older than 24 months. A molecular study on a Brazilian cohort (age range 0-23 months has detected TEL/AML1+ve (N = 9, E2A/PBX1+ve (N = 4, PML/RARA+ve (N = 4, and AML1/ETO+ve (N = 2 cases. Undoubtedly, the great majority of genetic events occurring in these patients arise prenatally. The environmental exposure to damaging agents that give rise to genetic changes prenatally may be accurately determined in infants since the window of exposure is limited and known. Several studies have shown maternal exposures that may give rise to leukemogenic changes. The Brazilian Collaborative Study Group of Infant Acute Leukemia has found that mothers exposed to dipyrone, pesticides and hormones had an increased chance to give birth to babies with infant acute leukemia [OR = 1.48 (95%CI = 1.05-2.07, OR = 2.27 (95%CI = 1.56-3.31 and OR = 9.08 (95%CI = 2.95-27.96], respectively. This review aims to summarize recent clues that have facilitated the elucidation of the biology of early childhood leukemias, with emphasis on infant acute leukemia in the Brazilian population.

  2. An electronic screen for triaging adolescent substance use by risk levels.

    Science.gov (United States)

    Levy, Sharon; Weiss, Roger; Sherritt, Lon; Ziemnik, Rosemary; Spalding, Allegra; Van Hook, Shari; Shrier, Lydia A

    2014-09-01

    Screening adolescents for substance use and intervening immediately can reduce the burden of addiction and substance-related morbidity. Several screening tools have been developed to identify problem substance use for adolescents, but none have been calibrated to triage adolescents into clinically relevant risk categories to guide interventions. To describe the psychometric properties of an electronic screen and brief assessment tool that triages adolescents into 4 actionable categories regarding their experience with nontobacco substance use. Adolescent patients (age range, 12-17 years) arriving for routine medical care at 2 outpatient primary care centers and 1 outpatient center for substance use treatment at a pediatric hospital completed an electronic screening tool from June 1, 2012, through March 31, 2013, that consisted of a question on the frequency of using 8 types of drugs in the past year (Screening to Brief Intervention). Additional questions assessed severity of any past-year substance use. Patients completed a structured diagnostic interview (Composite International Diagnostic Interview-Substance Abuse Module), yielding Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) substance use diagnoses. For the entire screen and the Screening to Brief Intervention, sensitivity and specificity for identifying nontobacco substance use, substance use disorders, severe substance use disorders, and tobacco dependence were calculated using the Composite International Diagnostic Interview-Substance Abuse Module as the criterion standard. Of 340 patients invited to participate, 216 (63.5%) enrolled in the study. Sensitivity and specificity were 100% and 84% (95% CI, 76%-89%) for identifying nontobacco substance use, 90% (95% CI, 77%-96%) and 94% (95% CI, 89%-96%) for substance use disorders, 100% and 94% (95% CI, 90%-96%) for severe substance use disorders, and 75% (95% CI, 52%-89%) and 98% (95% CI, 95%-100%) for nicotine dependence. No significant

  3. Pregnancy, maternal tobacco smoking and early age leukemia in Brazil

    Directory of Open Access Journals (Sweden)

    Sergio eKoifman

    2012-11-01

    Full Text Available Background: Cigarette smoking has been associated with acute myeloid leukemia but hypothesis on the association between maternal smoking during pregnancy and childhood leukemia is unclear. Objectives: To investigate the association between maternal exposure to tobacco smoking during pregnancy and early age (< 2 yr. leukemia (EAL. Methods: A hospital-based multicenter case-control study aiming to explore EAL risk factors was carried out in Brazil during 1999-2007. Data were collected by direct interview with the biological mothers using a standardized questionnaire. The present study included 675 children, being 193 acute lymphoblastic leukemia (ALL, 59 acute myeloid leukemia (AML, and 423 controls, being the latter age frequency matched and paired by area of residence with the cases. Unconditional logistic regression was performed, and odds ratios (OR on the association between tobacco smoking (3 months before pregnancy, during pregnancy, and 3 months after delivery and EAL were ascertained after adjustment for selected variables (maternal age at birth and education, birth weight, infant skin color, and oral contraceptives use during pregnancy.Results: Smoking was reported by 17.5% of case mothers and 20.6% of controls´. Among women who reported to have smoked 20 or more cigarettes during the index pregnancy, an adjusted OR = 5.28 (95% C.I. 1.40-19.95 for ALL was observed. Heavy smoking during breastfeeding yielded an adjusted risk estimate for ALL, OR = 7.78 (95% C.I. 1.33-45.5. No dose-response effect was observed according to smoking exposure during pregnancy and EAL. An association between secondhand smoking during pregnancy or breastfeeding was not observed. Conclusion: An association between maternal smoking and AAL in the offspring was restricted to women who have reported an intense exposure to tobacco smoke during pregnancy and breastfeeding.

  4. Hormonal contraception among electronic cigarette users and cardiovascular risk: a systematic review.

    Science.gov (United States)

    Riley, Halley E M; Berry-Bibee, Erin; England, Lucinda J; Jamieson, Denise J; Marchbanks, Polly A; Curtis, Kathryn M

    2016-03-01

    Women who use combined hormonal contraceptives and cigarettes have an increased risk for cardiovascular (CV) events. We reviewed the literature to determine whether women who use hormonal contraceptives (HC) and electronic cigarettes (e-cigarettes) also have an increased risk. Systematic review. We searched for articles reporting myocardial infarction (MI), stroke, venous thromboembolism, peripheral arterial disease or changes to CV markers in women using e-cigarettes and HC. We also searched for indirect evidence, such as CV outcomes among e-cigarette users in the general population and among HC users exposed to nicotine, propylene glycol or glycerol. No articles reported on outcomes among e-cigarette users using HC. Among the general population, 13 articles reported on heart rate or blood pressure after e-cigarette use. These markers generally remained normal, even when significant changes were observed. In three studies, changes were less pronounced after e-cigarette use than cigarette use. One MI was reported among 1012 people exposed to e-cigarettes in these studies. One article on nicotine and HC exposure found both exposures to be significantly associated with acute changes to heart rate, though mean heart rate remained normal. No articles on propylene glycol or glycerol and HC exposure were identified. We identified no evidence on CV outcomes among e-cigarette users using HC. Limited data reporting mostly acute outcomes suggested that CV events are rare among e-cigarette users in the general population and that e-cigarettes may affect heart rate and blood pressure less than conventional cigarettes. There is a need for research assessing joint HC and e-cigarette exposure on clinical CV outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Electronic Health Record Tools to Care for At-Risk Older Drivers: A Quality Improvement Project.

    Science.gov (United States)

    Casey, Colleen M; Salinas, Katherine; Eckstrom, Elizabeth

    2015-06-01

    Evaluating driving safety of older adults is an important health topic, but primary care providers (PCP) face multiple barriers in addressing this issue. The study's objectives were to develop an electronic health record (EHR)-based Driving Clinical Support Tool, train PCPs to perform driving assessments utilizing the tool, and systematize documentation of assessment and management of driving safety issues via the tool. The intervention included development of an evidence-based Driving Clinical Support Tool within the EHR, followed by training of internal medicine providers in the tool's content and use. Pre- and postintervention provider surveys and chart review of driving-related patient visits were conducted. Surveys included self-report of preparedness and knowledge to evaluate at-risk older drivers and were analyzed using paired t-test. A chart review of driving-related office visits compared documentation pre- and postintervention including: completeness of appropriate focused history and exam, identification of deficits, patient education, and reporting to appropriate authorities when indicated. Data from 86 providers were analyzed. Pre- and postintervention surveys showed significantly increased self-assessed preparedness (p < .001) and increased driving-related knowledge (p < .001). Postintervention charts showed improved documentation of correct cognitive testing, more referrals/consults, increased patient education about community resources, and appropriate regulatory reporting when deficits were identified. Focused training and an EHR-based clinical support tool improved provider self-reported preparedness and knowledge of how to evaluate at-risk older drivers. The tool improved documentation of driving-related issues and led to improved access to interdisciplinary care coordination. Published by Oxford University Press on behalf of the Gerontological Society of America 2015.

  6. Determination of leukemia-associated gene rearrangements and ultrastructural changes in Chernobyl accident liquidators blood leukocytes long term after radiation exposure

    International Nuclear Information System (INIS)

    Butenko, Z.A.; Smirnova, I.A.; Yanok, E.A.; Kishinskaya, E.G.; Zak, K.P.; Afanas'eva, V.V.; Mikhajlovskaya, Eh.V.

    1997-01-01

    The results of ultrastructural and molecular-genetic investigations of blood cells from 120 liquidators 7-10 years after Chernobyl accident with the total exposure radiation doses ranging from 5.1 to 75.0 cGy are presented. Electron microscopic studies revealed marked changes in ultrastructure of neutrophils nuclei - hyper segmentation, whimsical prominences, loops, swelling and destruction of cytoplasmic granules. There was an increase in the number of 'aberrant' forms of lymphocytes with disturbed structure of chromatin, additional nuclei and changed membrane contour. Structural polymorphism of the leukemia associated bcr and ribosomal RNA (rRNA) genes were studied using Southern blot hybridization. Allelic polymorphism of bcr gene with characteristic for chronic myeloid leukemia allele distribution and rearrangements of eRNA genes were detected in 11.5% of accident liquidators. This data point out to structure-functional leucocyte changes and possibility of arising leukemia associated gene rearrangements in blood cells of some liquidators many years after the exposure to radiation and serve for determination of group at risk of oncohematological diseases

  7. Association of leukemia with radium groundwater contamination

    International Nuclear Information System (INIS)

    Lyman, G.H.; Lyman, C.G.; Johnson, W.

    1985-01-01

    Radiation exposure, including the ingestion of radium, has been causally associated with leukemia in man. Groundwater samples from 27 counties on or near Florida phosphate lands were found to exceed 5 pCi/L total radium in 12.4% of measurements. The incidence of leukemia was greater in those counties with high levels of radium contamination (greater than 10% of the samples contaminated) than in those with low levels of contamination. Rank correlation coefficients of .56 and .45 were observed between the radium contamination level and the incidence of total leukemia and acute myeloid leukemia, respectively. The standardized incidence density ratio for those in high-contamination counties was 1.5 for total leukemia and 2.0 for acute myeloid leukemia. Further investigation is necessary, however, before a causal relationship between groundwater radium content and human leukemia can be established

  8. High syndecan-1 levels in acute myeloid leukemia are associated with bleeding, thrombocytopathy, endothelial cell damage, and leukocytosis

    DEFF Research Database (Denmark)

    Larsen, Anne Mette Vestskov; Leinøe, Eva Birgitte; Johansson, Pär I

    2013-01-01

    The risk of hemorrhage is influenced by multiple factors in acute myeloid leukemia (AML). We investigated whether hemorrhage in AML patients was associated with endothelial perturbation, potentially caused by thrombocytopenia, platelet dysfunction and leukocytosis. Biomarkers of endothelial...

  9. Population prevalence and control of cardiovascular risk factors: what electronic medical records tell us.

    Science.gov (United States)

    Catalán-Ramos, Arantxa; Verdú, Jose M; Grau, María; Iglesias-Rodal, Manuel; del Val García, José L; Consola, Alicia; Comin, Eva

    2014-01-01

    To analyze the prevalence, control, and management of hypertension, hypercholesterolemia, and diabetes mellitus type 2 (DM2). Cross-sectional analysis of all individuals attended in the Catalan primary care centers between 2006 and 2009. History of cardiovascular diseases, diagnosis and treatment of hypertension, hypercholesterolemia, DM2, lipid profile, glycemia and blood pressure data were extracted from electronic medical records. Age-standardized prevalence and levels of management and control were estimated. Individuals aged 35-74 years using primary care databases. A total of 2,174,515 individuals were included (mean age 52 years [SD 11], 47% men). Hypertension was the most prevalent cardiovascular risk factor (39% in women, 41% in men) followed by hypercholesterolemia (38% and 40%) and DM2 (12% and 16%), respectively. Diuretics and angiotensin-converting enzyme inhibitors were most often prescribed for hypertension control (women treated). Hypercholesterolemia was controlled (low-density lipoprotein cholesterol women with no history of cardiovascular disease, despite lipid-lowering treatment, primarily (90%) with statins. The percentage of women and men with DM2 and with glycated hemoglobin DM2 were adequately controlled; hypercholesterolemia control was particularly low. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  10. Risk factors for medication errors in the electronic and manual prescription.

    Science.gov (United States)

    Volpe, Cris Renata Grou; Melo, Eveline Maria Magalhães de; Aguiar, Lucas Barbosa de; Pinho, Diana Lúcia Moura; Stival, Marina Morato

    2016-08-08

    to compare electronic and manual prescriptions of a public hospital of Brasilia, identifying risk factors for the occurrence of medication errors. descriptive-exploratory, comparative and retrospective study. Data collection occurred from July 2012 to January 2013, using an instrument for the review of the information contained in medical records related to the medication process. A total of 190 manual and 199 electronic records composed the sample, with 2027 prescriptions each. compared to the manual prescription, a significant reduction was observed in the risk factors after implantation of the electronic prescription, in items such as "lack of the form of dilution" (71.1% to 22.3%) and "prescription with brand name" (99.5% to 31.5%). Conversely, the risk factors "no check" and "lack of CRM of the prescriber" increased. The lack of the allergy registration and the occurrences related to medication were the same for both groups. generally, the use of the electronic prescription system was associated with a significant reduction in risk factors for medication errors, concerning the following aspects: illegibility, prescription with brand name and presence of essential items that provide a safe and effective prescription. comparar as prescrições eletrônicas e manuais de um hospital público do Distrito Federal, identificando os fatores de risco para ocorrência de erros de medicação. Estudo descritivo-exploratório, comparativo e retrospectivo. A coleta de dados ocorreu no período de julho de 2012 a janeiro de 2013, através de instrumento para revisão das informações referentes ao processo de medicação contidas em prontuários. Integraram a amostra 190 prontuários manuais e 199 eletrônicos, com 2027 prescrições cada. na comparação com a prescrição manual, observou-se redução significativa dos fatores de risco após implantação da eletrônica, em itens como "falta da forma de diluição" (71,1% e 22,3%) e "prescrição com nome comercial" (99

  11. Cardiac implantable electronic device hematomas: Risk factors and effect of prophylactic pressure bandaging.

    Science.gov (United States)

    Koh, Youlin; Bingham, Nicholas E; Law, Natalie; Le, Dustin; Mariani, Justin A

    2017-07-01

    Cardiac implantable electronic device (CIED) hematomas are associated with many adverse outcomes. We examined the incidence and risk factors associated with hematoma formation post-CIED implantation, and explored the preventative effect of prophylactic pressure bandaging (PPB) in a large tertiary center. 1,091 devices were implanted during October 2011-December 2014. Clinically significant hematomas (CSH) were those that necessitated prolonged admission, including those due to reoperation, and clinically suspicious hematomas were swellings noted by medical/nursing staff. We screened for variables affecting hematoma incidence prior to conducting multivariate logistic regression analyses, one for all hematomas and one for CSH. 61 hematomas were identified (5.6% of patients), with 12 of those clinically significant (1.1% of patients). Factors significantly increasing the odds of developing any hematoma were stage 2 (odds ratio [OR] = 2.93, 95% confidence interval [CI] [1.08-7.94], P = 0.034) and 3 chronic kidney disease (CKD) (OR = 3.39 [1.20-9.56], P = 0.021), unfractionated heparin/therapeutic enoxaparin (OR = 3.15 [1.22-8.14], P = 0.018), and dual antiplatelets-aspirin + clopidogrel (OR = 2.95 [1.14-7.65], P = 0.026) + other combinations. Body Mass index (BMI) 25.0-29.9 (OR 0.52 [0.28-0.98], P = 0.044) and >30 were associated with decreased hematoma risk (OR 0.43 [0.20-0.91], P = 0.028). Factors significant for CSH formation were unfractionated heparin/therapeutic enoxaparin (OR = 9.55 [1.83-49.84], P = 0.007) and aspirin + clopidogrel (OR = 7.19 [1.01-50.91], P = 0.048). PPB nonsignificantly increased the odds of total hematoma development (OR = 1.53 [0.87-2.69], P = 0.135), and reduced CSH (OR = 0.67 [0.18-2.47], P = 0.547). Heparin and dual antiplatelet use remain strong predictors of overall hematoma formation. CKD is a comparatively moderate predictor. BMI > 25 may decrease the risk of hematoma formation. PPB had nonsignificant effects on hematoma development

  12. Driving Toward Precision Medicine for Acute Leukemias: Are We There Yet?

    Science.gov (United States)

    Chung, Clement; Ma, Hilary

    2017-09-01

    Despite recent progress in the understanding of the molecular basis of acute leukemias, treatment options for these diseases have not changed significantly over the last few decades. We present a nonexhaustive summary of the current cytogenetic and molecular changes associated with acute leukemias in disease prognostication and potential targeted therapies. An emerging paradigm is that many genetic or molecular alterations target similar signal transduction, transcriptional, and epigenetic pathways. Some of these targets may be used as predictive biomarkers for the development of novel targeted therapies that depart significantly from conventional chemotherapy, the current mainstay for the treatment of acute leukemias. Established leukemia-specific predictive biomarkers for precision medicine include those genetic lesions such as BCR-ABL1 for Philadelphia-positive acute lymphoblastic leukemia and PML-RARα for acute promyelocytic leukemia. Evidence indicates that targeted therapy for FLT-ITD gene mutations with small-molecule tyrosine kinase inhibitors can extend its use from relapsed disease to up-front induction therapy. Core-binding factor acute myeloid leukemia in adults predicts benefit with high-dose cytarabine in the absence of KIT mutation. Although risk-adapted therapy based on genetic abnormalities in acute leukemias has allowed the beginning of personalized treatment and selective use of hematopoietic stem cell transplantation, the prognostic and/or predictive value of many novel mutations of the acute leukemic genome is yet to be elucidated. Many challenges lie ahead in targeted therapies due to overlapping of chromosomal and molecular lesions as well as other limiting factors. Future work should focus on the understanding of pathogenetic changes that lead to leukemogenesis, which may guide the rational design of new targeted therapies and make the drive toward precision medicine for acute leukemias one step closer. © 2017 Pharmacotherapy Publications

  13. INCIDENCE OF ACUTE MYELOID LEUKEMIA AFTER BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Caterina Giovanna Valentini

    2011-12-01

    Full Text Available Breast cancer is the most frequent cancer among women and the leading cause of death among middle-aged women. Early detection by mammography screening and improvement of therapeutic options have increased breast cancer survival rates, with the consequence that late side effects of cancer treatment become increasingly important. In particular, patients treated with adjuvant chemotherapy regimens, commonly including alkylating agents and anthracyclines, are at increased risk of developing leukemia, further enhanced by the use of radiotherapy. In the last few years also the use of growth factors seems to increase the risk of secondary leukemia. The purpose of this review is to update epidemiology of therapy-related myeloid neoplasms occurring in breast cancer patients

  14. The epidemiological studies of leukemia around nuclear installations for children and young adults: synthesis of the critical review

    International Nuclear Information System (INIS)

    2008-01-01

    An epidemiological study published at the end of 2007 described an increased risk of leukemia among children less than five years leaving at less than 5 kilometers from German nuclear power plants. The objective of this report was to make a synthesis and a critical analysis of the results relative to the risk of leukemia among the children and young adults of less than twenty five years leaving near these nuclear installations. (N.C.)

  15. Acute myelomonocytic leukemia following splenectomy in a patient with long-standing Hodgkin disease

    International Nuclear Information System (INIS)

    Rosenbloom, B.E.; Klein, E.J.; Uszler, J.M.; Ellis, R.; Block, J.B.; Tanaka, K.R.

    1978-01-01

    The association of acute nonlymphocytic leukemia with Hodgkin disease has been recorded in more than 100 instances. In most of these cases the patient has had long-standing Hodgkin disease and radiotherapy has been carried out. The combination of previous radiotherapy and chemotherapy appears to further increase the risk of leukemia developing. In a patient under our care with Hodgkin disease acute myelomonocytic leukemia developed following splenectomy for hypersplenism. The onset of acute leukemia immediately following splenectomy in a patient with Hodgkin disease has not previously been noted. In addition, because the patient's usual bone marrow sampling sites were hypoplastic, we utilized an 111 In-chloride bone marrow scan to find a site that was accessible for aspiration

  16. Thromboembolism in Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Rank, Cecilie Utke; Toft, Nina; Tuckuviene, Ruta

    2018-01-01

    Thromboembolism frequently occurs during acute lymphoblastic leukemia (ALL) therapy. We prospectively registered thromboembolic events during treatment of 1772 consecutive Nordic/Baltic ALL patients 1-45years treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL...

  17. Heterogeneity in acute undifferentiated leukemia.

    Science.gov (United States)

    LeMaistre, A; Childs, C C; Hirsch-Ginsberg, C; Reuben, J; Cork, A; Trujillo, J M; Andersson, B; McCredie, K B; Freireich, E; Stass, S A

    1988-01-01

    From January 1985 to May 1987, we studied 256 adults with newly diagnosed acute leukemia. Acute undifferentiated leukemia (AUL) was diagnosed in 12 of the 256 (4.6%) cases when lineage could not be delineated by light microscopy and light cytochemistry. To further characterize the blasts, immunophenotyping, ultrastructural myeloperoxidase (UMPO), and ultrastructural platelet peroxidase parameters were examined in 10, 11, and 6 of the 12 cases, respectively. Five cases demonstrated UMPO and were reclassified as acute myeloblastic leukemia (AML). Of the six UMPO-negative cases, three had a myeloid and one had a mixed immunophenotype. One UMPO-negative patient with a myeloid immunophenotype was probed for the immunoglobulin heavy chain gene (JH) and the beta chain of the T-cell receptor gene (Tcr beta) with no evidence of rearrangement. Six cases were treated with standard acute lymphoblastic leukemia (ALL) chemotherapy and failed to achieve complete remission (CR). Various AML chemotherapeutic regimens produced CR in only 3 of the 12 cases. One case was treated with gamma interferon and the other 2 with high-dose Ara-C. Our findings indicate a myeloid lineage can be detected by UMPO (5/12) in some cases of AUL. A germline configuration with JH and Tcr beta in one case as well as a myeloid immunophenotype in 3 UMPO-negative cases raises the possibility that myeloid lineage commitment may occur in the absence of myeloid peroxidase (MPO) cytochemical positivity.

  18. Clinical Presentations of Acute Leukemia

    International Nuclear Information System (INIS)

    Shahab, F.; Raziq, F.

    2014-01-01

    Objective: To document the clinical presentation and epidemiology of various types of acute leukemia with their respective referral source at a tertiary level centre in Peshawar. Study Design: An observational study. Place and Duration of Study: Department of Pathology, Hayatabad Medical Complex (HMC), Peshawar, from January 2011 to May 2012. Methodology: A total of 618 bone marrow biopsy reports were reviewed. All biopsy reports labeled as acute leukemia were reviewed for age, gender, address, referring unit, diagnosis on bone marrow examination, presenting complaints, duration of illness and findings of clinical examination. Results: Ninety-two patients were diagnosed as suffering from acute leukemias (15%). ALL was most prevalent (46%), followed by AML (38%) and undifferentiated acute leukemia (16%). Males were affected more compared to females (60% vs. 40%). ALL and AML were predominant in pediatric (64%) and adults (77%) patients respectively. Patients from Afghanistan accounted for 33% of all cases followed by Peshawar (14%). Fever (77%), pallor (33%) and bleeding disorders (23%) were the main presenting complaints. Enlargement of liver, spleen and lymph nodes together was associated with ALL compared with AML (p = 0.004). Conclusion: ALL-L1 and AML-M4 were the most common sub-types. Fever, pallor and bleeding disorders were the main presenting complaints. Enlargement of liver, spleen and lymph nodes was more frequently associated with ALL compared to AML. (author)

  19. on Lymphoblastic Leukemia Jurkat Cells

    African Journals Online (AJOL)

    human tumor cell line (Hela) by using MTT assay. [13]. In the present study, we have observed the cytotoxic effect of ethanolic extract of C. arvensis against Jurkat cells, a human lymphoblastic leukemia cell line, by using Trypan blue, MTS assay and FACS analysis. It was shown from the trypan blue exclusion assay that ...

  20. Childhood Acute Lymphoblastic Leukemia and Indicators of Early Immune Stimulation: A Childhood Leukemia International Consortium Study

    Science.gov (United States)

    Rudant, Jérémie; Lightfoot, Tracy; Urayama, Kevin Y.; Petridou, Eleni; Dockerty, John D.; Magnani, Corrado; Milne, Elizabeth; Spector, Logan G.; Ashton, Lesley J.; Dessypris, Nikolaos; Kang, Alice Y.; Miller, Margaret; Rondelli, Roberto; Simpson, Jill; Stiakaki, Eftichia; Orsi, Laurent; Roman, Eve; Metayer, Catherine; Infante-Rivard, Claire; Clavel, Jacqueline

    2015-01-01

    The associations between childhood acute lymphoblastic leukemia (ALL) and several proxies of early stimulation of the immune system, that is, day-care center attendance, birth order, maternally reported common infections in infancy, and breastfeeding, were investigated by using data from 11 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980–2010). The sample included 7,399 ALL cases and 11,181 controls aged 2–14 years. The data were collected by questionnaires administered to the parents. Pooled odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Day-care center attendance in the first year of life was associated with a reduced risk of ALL (odds ratio = 0.77, 95% confidence interval: 0.71, 0.84), with a marked inverse trend with earlier age at start (P < 0.0001). An inverse association was also observed with breastfeeding duration of 6 months or more (odds ratio = 0.86, 95% confidence interval: 0.79, 0.94). No significant relationship with a history of common infections in infancy was observed even though the odds ratio was less than 1 for more than 3 infections. The findings of this large pooled analysis reinforce the hypothesis that day-care center attendance in infancy and prolonged breastfeeding are associated with a decreased risk of ALL. PMID:25731888

  1. A qualitative assessment of the perceived risks of electronic cigarette and hookah use in pregnancy.

    Science.gov (United States)

    Kahr, Maike K; Padgett, Shannon; Shope, Cindy D; Griffin, Emily N; Xie, Susan S; Gonzalez, Pablo J; Levison, Judy; Mastrobattista, Joan; Abramovici, Adi R; Northrup, Thomas F; Stotts, Angela L; Aagaard, Kjersti M; Suter, Melissa A

    2015-12-21

    Studies reveal that electronic cigarette (e-cigarette) and hookah use are increasing among adolescents and young adults. However, the long-term health effects are unknown, especially with regards to pregnancy. Because of the increased use in women of reproductive age, and the unknown long-term health risks, our primary objectives were to determine the perceived risks of e-cigarette and hookah use in pregnancy, and learn common colloquial terms associated with e-cigarettes. Furthermore, we sought to determine if there is a stigma associated with e-cigarette use in pregnancy. Eleven focus groups including 87 participants were conducted immediately following regularly scheduled CenteringPregnancy® prenatal care with women at three different clinics in the greater Houston area. A minimum of two facilitators led the groups, using ten lead-in prompts, with Spanish translation as necessary. Facilitators took notes which were compared immediately following each group discussion and each group was audio recorded and transcribed. Three facilitators utilized NVivo 9.0 software to organize the transcribed data into nodes to identify major themes. To increase rigor, transcripts were further analyzed by two obstetricians who were instructed to find the major themes. Analyses revealed contradicting themes concerning e-cigarette use. In general, e-cigarettes were perceived as safer alternatives to regular tobacco cigarettes, especially if used as smoking cessation devices. A major theme is that use in pregnancy is harmful to the fetus. However, it was perceived that use for smoking cessation in pregnancy may have fewer side effects. We found that a common term for e-cigarettes is "Blu." In our discussion of hookah use, participants perceived use as popular among teenagers and that use in pregnancy is dangerous for the fetus. Although a strong theme emerged against hookah use, we found contradicting themes in our discussions on e-cigarette use in pregnancy. It is possible that e

  2. Aberrant megakaryocytopoiesis preceding radiation-induced leukemia in the dog

    International Nuclear Information System (INIS)

    Tolle, D.V.; Seed, T.M.; Cullen, S.M.; Poole, C.M.; Fritz, T.E.

    1982-01-01

    Six of nine decedent beagles exposed continuously to 2.5 R*/22 hour day of whole-body 60Co gamma-radiation died with myeloproliferative diseases: three cases of myelogenous leukemia and one each of monocytic leukemia, erythroleukemia, and erythremic myelosis. The three dogs that died with myelogenous leukemia had micromegakaryocytes and megakaryoblasts in the peripheral blood during the preleukemic phase when myeloblasts were not observed in the peripheral blood or in increased numbers in the bone marrow. In this study we have examined the megakaryocytes during the preleukemic period by a combination of light, transmission, and scanning electron microscopy. Morphologic abnormalities seen by light microscopy included mononucleated and binucleated forms, many with cytoplasmic blebs. The small mononuclear forms in the bone marrow tended to form clusters. Ultrastructural features included a paucity of both specific alpha granules and dense granules. The micromegakaryocytes showed dysgenesis of the demarcation membrane system. This membrane system appeared disorganized with a few dilated round, oval, or rarely, elongated vesicles and showed no evidence of platelet formation. The cells also had a paucity of endoplasmic reticulum, few mitochrondria, and sparse glycogen accumulations. The scarcity of cytoplasmic organelles gave a pale immature appearance to the cytoplasm. By scanning electron microscopy, the sponge-like surface of large mature megakaryocytes from unirradiated marrow contrasted with the characteristically smooth, topographically featureless surfaces of the micromegakaryocytes from preleukemic dogs

  3. Aberrant megakaryocytopoiesis preceding radiation-induced leukemia in the dog

    International Nuclear Information System (INIS)

    Tolle, D.V.; Seed, T.M.; Cullen, S.M.; Poole, C.M.; Fritz, T.E.

    1982-01-01

    Six of nine decedent beagles exposed continuously to 2.5 R/22 hour day of whole-body 60 Co γ-radiation died with myeloproliferative diseases: three cases of myelogenous leukemia and one each of monocytic leukemia, erythroleukemia, and erythremic myelosis. The three dogs that died with myelogenous leukemia had micromegakaryocytes and megakaryoblasts in the peripheral blood during the preleukemic phase when myeloblasts were not observed in the peripheral blood or in increased numbers in the bone marrow. In this study we have examined the megakaryocytes during the preleukemic period by a combination of light, transmission, and scanning electron microscopy. Morphologic abnormalities seen by light microscopy included mononucleated and binucleated forms, many with cytoplasmic blebs. The small mononuclear forms in the bone marrow tended to form clusters. Ultrastructural features included a paucity of both specific α granules and dense granules. The micromegakaryocytes showed dysgenesis of the demarcation membrane system. This membrane system appeared disorganized with a few dilated round, oval, or rarely, elongated vesicles and showed no evidence of platelet formation. The cells also had a paucity of endoplasmic reticulum, few mitochrondria, and sparse glycogen accumulations. The scarcity of cytoplasmic organelles gave a pale immature appearance to the cytoplasm. By scanning electron microscopy, the sponge-like surface of large mature megakaryocytes from unirradiated marrow contrasted with the characteristically smooth, topographically featureless surfaces of the micromegakaryocytes from preleukemic dogs

  4. ALLOGENEIC TRANSPLANTATION FOR CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Patrizia Chiusolo

    2010-05-01

    Full Text Available

    Even if Chronic lymphocytic leukemia (CLL often has an indolent behavior with good responsiveness to cytoreductive treatment, about 20% of the patients, so called "poor-risk" patients, show an aggressive course and die within a few years despite early intensive therapies. Criteria for poor-risk disease according to the European Bone Marrow Transplantation (EBMT CLL Transplant Consensus are: purine analogue refractoriness, early relapse after purine analogue combination therapy, CLL with p53 lesion requiring treatment.

    Allogeneic transplant has potential curative role in CLL, however burden with very  high transplant related mortality (TRM rates of 38-50%:

    A major advance in reducing the short-term morbidity and mortality of allogeneic stem cell transplantation (SCT has been the introduction of non-myeloablative or reduced intensity conditioning (RIC regimens to allow engraftment of allogeneic stem cells. There is no doubt that the crucial therapeutic principle of allo-SCT in CLL is graft versus leukemia (GVL activity.

    The major complications of allogeneic SCT in CLL are: chronic graft-versus-host-disease (GVHD affecting quality of life, high graft rejection and infection rates rates correlated with preexisting immunosuppression. Disease relapse remains the major cause of failure after RIC allo-HCT in CLL patients.

    Sensitive minimal residual disease (MRD quantification has strong prognostic impact after transplant.

     

  5. Low-dose total skin electron beam therapy for cutaneous lymphoma : Minimal risk of acute toxicities.

    Science.gov (United States)

    Kroeger, Kai; Elsayad, Khaled; Moustakis, Christos; Haverkamp, Uwe; Eich, Hans Theodor

    2017-12-01

    Low-dose total skin electron beam therapy (TSEBT) is attracting increased interest for the effective palliative treatment of primary cutaneous T‑cell lymphoma (pCTCL). In this study, we compared toxicity profiles following various radiation doses. We reviewed the records of 60 patients who underwent TSEBT for pCTCL between 2000 and 2016 at the University Hospital of Munster. The treatment characteristics of the radiotherapy (RT) regimens and adverse events (AEs) were then analyzed and compared. In total, 67 courses of TSEBT were administered to 60 patients. Of these patients, 34 (51%) received a standard dose with a median surface dose of 30 Gy and 33 patients (49%) received a low dose with the median surface dose of 12 Gy (7 salvage low-dose TSEBT courses were administered to 5 patients). After a median follow-up of 15 months, the overall AE rate was 100%, including 38 patients (57%) with grade 2 and 7 (10%) with grade 3 AEs. Patients treated with low-dose TSEBT had significantly fewer grade 2 AEs than those with conventional dose regimens (33 vs. 79%, P dose regimen compared to those with the conventional dose regimens (6 vs. 15%, P = 0.78). Multiple/salvage low-dose TSEBT courses were not associated with an increased risk of acute AEs. Low-dose TSEBT regimens are associated with significantly fewer grade 2 acute toxicities compared with conventional doses of TSEBT. Repeated/Salvage low-dose TSEBT, however, appears to be tolerable and can even be applied safely in patients with cutaneous relapses.

  6. A Regularized Deep Learning Approach for Clinical Risk Prediction of Acute Coronary Syndrome Using Electronic Health Records.

    Science.gov (United States)

    Huang, Zhengxing; Dong, Wei; Duan, Huilong; Liu, Jiquan

    2018-05-01

    Acute coronary syndrome (ACS), as a common and severe cardiovascular disease, is a leading cause of death and the principal cause of serious long-term disability globally. Clinical risk prediction of ACS is important for early intervention and treatment. Existing ACS risk scoring models are based mainly on a small set of hand-picked risk factors and often dichotomize predictive variables to simplify the score calculation. This study develops a regularized stacked denoising autoencoder (SDAE) model to stratify clinical risks of ACS patients from a large volume of electronic health records (EHR). To capture characteristics of patients at similar risk levels, and preserve the discriminating information across different risk levels, two constraints are added on SDAE to make the reconstructed feature representations contain more risk information of patients, which contribute to a better clinical risk prediction result. We validate our approach on a real clinical dataset consisting of 3464 ACS patient samples. The performance of our approach for predicting ACS risk remains robust and reaches 0.868 and 0.73 in terms of both AUC and accuracy, respectively. The obtained results show that the proposed approach achieves a competitive performance compared to state-of-the-art models in dealing with the clinical risk prediction problem. In addition, our approach can extract informative risk factors of ACS via a reconstructive learning strategy. Some of these extracted risk factors are not only consistent with existing medical domain knowledge, but also contain suggestive hypotheses that could be validated by further investigations in the medical domain.

  7. Chronic Myeloid Leukemia

    Science.gov (United States)

    ... the survivors of the atomic-bomb blast in Japan. A slight increase in risk also occurs in ... 2013;14(14):1977-1986. National Comprehensive Cancer Network. Practice Guidelines ... oncology social workers, nurses and health educators who are available ...

  8. Genetics Home Reference: PDGFRB-associated chronic eosinophilic leukemia

    Science.gov (United States)

    ... associated chronic eosinophilic leukemia PDGFRB-associated chronic eosinophilic leukemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description PDGFRB -associated chronic eosinophilic leukemia is a type of cancer of blood-forming ...

  9. Study Gaps Relevant to Use of Complementary Medicine in Patients With Leukemia: A Review Study

    Directory of Open Access Journals (Sweden)

    Miladinia

    2016-04-01

    Full Text Available Context A review of the literature of recent decades has shown that few studies have been conducted on the effects of various types of complementary medicine on patients with leukemia. Therefore, the present study aimed to find research gaps in the use of different types of complementary medicine in patients with leukemia to be applied in future studies. Evidence Acquisition The present study was a review-type design based on a review of the literature on different types of complementary medicine in patients with leukemia, up to 2015. The search was conducted through electronic databases and search engines. According to the inclusion and exclusion criteria, 8 studies which had been conducted on the use of complementary medicine in patients with leukemia were selected for the identification of gaps. Results The overall results showed that few studies have been conducted on the use of exercise, massage therapy, music therapy, acupressure, and healing touch in patients with leukemia, and these subjects are potential research areas for many different studies. However, no studies have been carried out on the effects of acupuncture, relaxation, and yoga on these patients. Conclusions The results of this review showed that the number of studies on the use of complementary medicine in leukemia patients is very limited (especially in Iran, and it can be the subject of numerous studies in the future.

  10. Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    For acute lymphoblastic leukemia (ALL), the 5-year survival rate has improved significantly since 1975. Get information about risk factors, signs, diagnosis, molecular features, survival, risk-based treatment assignment, and induction and postinduction therapy for children and adolescents with newly diagnosed and recurrent ALL.

  11. The Danish National Acute Leukemia Registry

    DEFF Research Database (Denmark)

    Østgård, Lene Sofie Granfeldt; Nørgaard, Jan Maxwell; Raaschou-Jensen, Klas Kræsten

    2016-01-01

    AIM OF DATABASE: The main aim of the Danish National Acute Leukemia Registry (DNLR) was to obtain information about the epidemiology of the hematologic cancers acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS). STUDY POPULATION: The registry...... was established in January 2000 by the Danish Acute Leukemia Group and has been expanded over the years. It includes adult AML patients diagnosed in Denmark since 2000, ALL patients diagnosed since 2005, and MDS patients diagnosed since 2010. The coverage of leukemia patients exceeds 99%, and the coverage of MDS...... years. To ensure this high coverage, completeness, and quality of data, linkage to the Danish Civil Registration System and the Danish National Registry of Patients, and several programmed data entry checks are used. CONCLUSION: The completeness and positive predictive values of the leukemia data have...

  12. Challenges in risk estimation using routinely collected clinical data: The example of estimating cervical cancer risks from electronic health-records.

    Science.gov (United States)

    Landy, Rebecca; Cheung, Li C; Schiffman, Mark; Gage, Julia C; Hyun, Noorie; Wentzensen, Nicolas; Kinney, Walter K; Castle, Philip E; Fetterman, Barbara; Poitras, Nancy E; Lorey, Thomas; Sasieni, Peter D; Katki, Hormuzd A

    2018-06-01

    Electronic health-records (EHR) are increasingly used by epidemiologists studying disease following surveillance testing to provide evidence for screening intervals and referral guidelines. Although cost-effective, undiagnosed prevalent disease and interval censoring (in which asymptomatic disease is only observed at the time of testing) raise substantial analytic issues when estimating risk that cannot be addressed using Kaplan-Meier methods. Based on our experience analysing EHR from cervical cancer screening, we previously proposed the logistic-Weibull model to address these issues. Here we demonstrate how the choice of statistical method can impact risk estimates. We use observed data on 41,067 women in the cervical cancer screening program at Kaiser Permanente Northern California, 2003-2013, as well as simulations to evaluate the ability of different methods (Kaplan-Meier, Turnbull, Weibull and logistic-Weibull) to accurately estimate risk within a screening program. Cumulative risk estimates from the statistical methods varied considerably, with the largest differences occurring for prevalent disease risk when baseline disease ascertainment was random but incomplete. Kaplan-Meier underestimated risk at earlier times and overestimated risk at later times in the presence of interval censoring or undiagnosed prevalent disease. Turnbull performed well, though was inefficient and not smooth. The logistic-Weibull model performed well, except when event times didn't follow a Weibull distribution. We have demonstrated that methods for right-censored data, such as Kaplan-Meier, result in biased estimates of disease risks when applied to interval-censored data, such as screening programs using EHR data. The logistic-Weibull model is attractive, but the model fit must be checked against Turnbull non-parametric risk estimates. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Diagnosis of large granular lymphocytic leukemia in a patient previously treated for acute myeloblastic leukemia

    OpenAIRE

    Sinem Civriz Bozdag; Sinem Namdaroglu; Omur Kayikci; Gülsah Kaygusuz; Itir Demiriz; Murat Cinarsoy; Emre Tekgunduz; Fevzi Altuntas

    2013-01-01

    Large granular lymphocytic (LGL) leukemia is a lymphoproliferative disease characterized by the clonal expansion of cytotoxic T or natural killer cells. We report on a patient diagnosed with T-cell LGL leukemia two years after the achievement of hematologic remission for acute myeloblastic leukemia.

  14. Targeting FLT3 Signaling in Childhood Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Amy N. Sexauer

    2017-11-01

    Full Text Available Acute myeloid leukemia (AML is the second most common leukemia of childhood and is associated with high rates of chemotherapy resistance and relapse. Clinical outcomes for children with AML treated with maximally intensive multi-agent chemotherapy lag far behind those of children with the more common acute lymphoblastic leukemia, demonstrating continued need for new therapeutic approaches to decrease relapse risk and improve long-term survival. Mutations in the FMS-like tyrosine kinase-3 receptor gene (FLT3 occur in approximately 25% of children and adults with AML and are associated with particularly poor prognoses. Identification and development of targeted FLT3 inhibitors represents a major precision medicine paradigm shift in the treatment of patients with AML. While further development of many first-generation FLT3 inhibitors was hampered by limited potency and significant toxicity due to effects upon other kinases, the more selective second- and third-generation FLT3 inhibitors have demonstrated excellent tolerability and remarkable efficacy in the relapsed/refractory and now de novo FLT3-mutated AML settings. While these newest and most promising inhibitors have largely been studied in the adult population, pediatric investigation of FLT3 inhibitors with chemotherapy is relatively recently ongoing or planned. Successful development of FLT3 inhibitor-based therapies will be essential to improve outcomes in children with this high-risk subtype of AML.

  15. Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

    Science.gov (United States)

    2017-03-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  16. Radiation in the treatment of meningeal leukemia

    International Nuclear Information System (INIS)

    Jenkin, R.D.

    1979-01-01

    At the present time, a successful regimen for the eradication of occult meningeal leukemia is the combination of cranial radiotherapy in a dose of 1800 rads in 10 fractions in 12 to 14 days with six doses of intrathecal methotrexate. This regimen, when given with prednisone and vincristine can be expected to give a relapse rate for isolated meningeal leukemia of approximately 5% during the first 2 years of follow-up. A modification of this regimen utilizing craniospinal radiation with prior and concurrent intrathecal methotrexate is given for the treatment of overt meningeal leukemia at diagnosis or for an isolated first relapse with meningeal leukemia. Radiation technique and morbidity are discussed

  17. Leukemia-associated antigens in man.

    Science.gov (United States)

    Brown, G; Capellaro, D; Greaves, M

    1975-12-01

    Rabbit antisera raised against acute lymphoblastic leukemia (ALL) cells were used to distinguish ALL from other leukemias, to identify rare leukemia cells in the bone marrow of patients in remission, and to define human leukemia-associated antigens. Antibody binding was studied with the use of immunofluorescence reagents and the analytic capacity of the Fluorescence Activated Cell Sorter-1 (FACS-1). The results indicated that most non-T-cell ALL have three leukemia-associated antigens on their surface which are absent from normal lymphoid cells: 1) an antigen shared with myelocytes, myeloblastic leukemia cells, and fetal liver (hematopoietic) cells; 2) an antigen shared with a subset of intermediate normoblasts in normal bone marrow and fetal liver; and 3) an antigen found thus far only on non-T-cell ALL and in some acute undifferentiated leukemias, which we therefore regard as a strong candidate for a leukemia-specific antigen. These antigens are absent from a subgroup of ALL patients in which the lymphoblasta express T-cell surface markers. Preliminary studies on the bone marrow samples of patients in remission indicated that rare leukemia cells were present in some samples. The implications of these findings with respect to the heterogeneity and cell origin(s) of ALL, its diagnosis, and its potential monitoring during treatment were discussed.

  18. Recurrence of acute myeloid leukemia in cryptorchid testis: case report

    International Nuclear Information System (INIS)

    Góes, Luccas Santos Patto de; Lopes, Roberto Iglesias; Campos, Octavio Henrique Arcos; Oliveira, Luiz Carlos Neves de; Sant'Anna, Alexandre Crippa; Dall'Oglio, Marcos Francisco; Srougi, Miguel

    2014-01-01

    A 23-year-old male with a history of bone marrow transplant for acute myeloid leukemia. He presented a large mass in the right inguinal region 5 years ago. Upon physical examination, right-sided cryptorchidism was observed. The tumor markers alpha-fetoprotein and beta-HCG were within normalcy range and lactate dehydrogenase was raised. Computed tomography of the abdomen and pelvis revealed right testicular mass in contiguity with the inguinal canal to the ipsilateral retroperitoneum, associated with right hydronephrosis. Due to the risk of germ-cell tumor in undescended testicle, the patient underwent radical right orchiectomy. The pathological examination showed recurrence of acute myeloid leukemia in the testis. He was referred to oncology for adjuvant therapy. Our literature review found no similar cases described

  19. Chronic Myeloid Leukemia In a Pregnant Woman: A Case Report

    Directory of Open Access Journals (Sweden)

    Aytekin Tokmak

    2015-12-01

    Full Text Available Chronic myeloid leukemia (CML is a rare disease in pregnancy. Our aim is to present a 37 weeks of pregnant woman with chronic myelogenous leukemia. A 27 Years in multigravi (gravida 5, parity: 4, at 37 weeks gestation was admitted with the diagnosis of painful pregnancy and CML. Physical examination findings were normal, complete blood count and peripheral blood smear results were consistent with CML. The patient was diagnosed CML in the 30th week of pregnancy and were treated with hydroxyurea and interferon. Treatment depends on the mother and the fetus did not develop any side effects. Our patient with CML is interesting due to lack of perinatal effects and take the diagnosis at an early age. CML diagnosed during pregnancy requires a multidisciplinary approach and hydroxyurea and interferon treatment on the mother and fetus are at low risk of inducing adverse effects. [Cukurova Med J 2015; 40(4.000: 811-813

  20. Acute lymphoblastic leukemia: a comprehensive review and 2017 update

    Science.gov (United States)

    Terwilliger, T; Abdul-Hay, M

    2017-01-01

    Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States alone. The hallmark of ALL is chromosomal abnormalities and genetic alterations involved in differentiation and proliferation of lymphoid precursor cells. In adults, 75% of cases develop from precursors of the B-cell lineage, with the remainder of cases consisting of malignant T-cell precursors. Traditionally, risk stratification has been based on clinical factors such age, white blood cell count and response to chemotherapy; however, the identification of recurrent genetic alterations has helped refine individual prognosis and guide management. Despite advances in management, the backbone of therapy remains multi-agent chemotherapy with vincristine, corticosteroids and an anthracycline with allogeneic stem cell transplantation for eligible candidates. Elderly patients are often unable to tolerate such regimens and carry a particularly poor prognosis. Here, we review the major recent advances in the treatment of ALL. PMID:28665419

  1. Recurrence of acute myeloid leukemia in cryptorchid testis: case report

    Energy Technology Data Exchange (ETDEWEB)

    Góes, Luccas Santos Patto de [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Lopes, Roberto Iglesias [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Campos, Octavio Henrique Arcos [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Oliveira, Luiz Carlos Neves de; Sant' Anna, Alexandre Crippa; Dall' Oglio, Marcos Francisco; Srougi, Miguel [Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-07-01

    A 23-year-old male with a history of bone marrow transplant for acute myeloid leukemia. He presented a large mass in the right inguinal region 5 years ago. Upon physical examination, right-sided cryptorchidism was observed. The tumor markers alpha-fetoprotein and beta-HCG were within normalcy range and lactate dehydrogenase was raised. Computed tomography of the abdomen and pelvis revealed right testicular mass in contiguity with the inguinal canal to the ipsilateral retroperitoneum, associated with right hydronephrosis. Due to the risk of germ-cell tumor in undescended testicle, the patient underwent radical right orchiectomy. The pathological examination showed recurrence of acute myeloid leukemia in the testis. He was referred to oncology for adjuvant therapy. Our literature review found no similar cases described.

  2. Using Electronic Health Records to Examine Disease Risk in Small Populations: Obesity Among American Indian Children, Wisconsin, 2007-2012.

    Science.gov (United States)

    Tomayko, Emily J; Weinert, Bethany A; Godfrey, Liz; Adams, Alexandra K; Hanrahan, Lawrence P

    2016-02-25

    Tribe-based or reservation-based data consistently show disproportionately high obesity rates among American Indian children, but little is known about the approximately 75% of American Indian children living off-reservation. We examined obesity among American Indian children seeking care off-reservation by using a database of de-identified electronic health records linked to community-level census variables. Data from electronic health records from American Indian children and a reference sample of non-Hispanic white children collected from 2007 through 2012 were abstracted to determine obesity prevalence. Related community-level and individual-level risk factors (eg, economic hardship, demographics) were examined using logistic regression. The obesity rate for American Indian children (n = 1,482) was double the rate among non-Hispanic white children (n = 81,042) (20.0% vs 10.6%, P American Indian children were less likely to have had a well-child visit (55.9% vs 67.1%, P American Indian records (18.3% vs 14.6%, P obesity risk among American Indian children (odds ratio, 1.8; 95% confidence interval, 1.6-2.1) independent of age, sex, economic hardship, insurance status, and geographic designation. An electronic health record data set demonstrated high obesity rates for nonreservation-based American Indian children, rates that had not been previously assessed. This low-cost method may be used for assessing health risk for other understudied populations and to plan and evaluate targeted interventions.

  3. Biologico-clinical significance of DNMT3A variants expression in acute myeloid leukemia.

    Science.gov (United States)

    Lin, Na; Fu, Wei; Zhao, Chen; Li, Bixin; Yan, Xiaojing; Li, Yan

    2017-12-09

    DNA methyltransferase 3A (DNMT3A) catalyzes de novo DNA methylation and plays important roles in the pathogenesis of acute myeloid leukemia. However, the expression status of DNMT3A variants in acute myeloid leukemia remains obscure. This study aimed to assess the expression levels of alternative splicing of DNMT3A variants and explore their roles in acute myeloid leukemia (AML). DNMT3A variants gene expression were assessed, measuring their effects on cell proliferation. In addition, the expression of DNMT3A variants were evaluated in acute myeloid leukemia patients. Four DNMT3A variants were identified, with DNMT3A1 and DNMT3A2V found to be dominant in acute myeloid leukemia cell lines. Moreover, DNMT3A2V overexpression delayed cell proliferation; while, DNMT3A2V R882H mutation promoted cell proliferation. Further, DNMT3A1 and DNMT3A2V were detected in newly diagnosed acute myeloid leukemia (AML) patients and controls with non-malignant hematological disease, with DNMT3A2V significantly up-regulated in AML patients. The main transcript switched from DNMT3A1 to DNMT3A2V in some patients, especially the low risk group based on the NCCN 2016 guidelines. These findings suggest that DNMT3A1 and DNMT3A2V are the main variants in acute myeloid leukemia with different clinical association, and might play important roles in the pathophysiology of acute myeloid leukemia. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. T-cell prolymphocytic leukemia

    OpenAIRE

    Graham, Robbie L.; Cooper, Barry; Krause, John R.

    2013-01-01

    T-cell prolymphocytic leukemia is a rare and unusual malignancy characterized by the proliferation of small- to medium-sized prolymphocytes of postthymic origin with distinctive clinical, morphologic, immunophenotypic, and cytogenetic features. Involvement of the peripheral blood, bone marrow, lymph nodes, liver, spleen, and skin can occur. The clinical course is typically very aggressive with poor response to conventional chemotherapy and short survival rates, and the only potential long-ter...

  5. Second acute leukemia and other malignancies following treatment for Hodgkin's disease

    International Nuclear Information System (INIS)

    Valagussa, P.; Santoro, A.; Fossati-Bellani, F.; Banfi, A.; Bonadonna, G.

    1986-01-01

    The records of 1329 patients with Hodgkin's disease admitted from 1965 to 1982 were analyzed to assess the relative frequency of second neoplasms. Within a median follow-up of 9.5 years, a total of 68 new cancers were documented. Nineteen cases of acute nonlymphocytic leukemia, 6 cases of non-Hodgkin's lymphomas, and 43 cases with different types of solid tumors were identified. The overall risk of non-Hodgkin's lymphoma was 1.3% +/- 0.6% and of solid tumors was 8.3% +/- 1.5% when basal cell carcinomas were included and 6.7% +/- 1.4% when basal cell carcinomas were excluded. No cases of leukemia were documented in patients treated with radiation therapy only. The 12-year estimate of leukemia by treatment was as follows: chemotherapy only 1.4% +/- 2.3%; radiation plus MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) 10.2% +/- 5.2%; radiation plus ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine) 0; and radiation plus other drug regimens 4.8% +/- 1.6%. The risk of leukemia was particularly high (15.5% +/- 7.4%) in patients who received salvage MOPP after radiation failure. A positive association was also noted between increasing age and risk of second malignancies, especially leukemia. The incidence of second neoplasms can be markedly decreased by deleting from potentially curative therapy certain drugs such as alkylating agents, procarbazine, and nitrosourea derivatives

  6. Bone marrow transplantation in severe aplastic anemia and acute or chronic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, U W; Mahmoud, H K; Beelen, D W; Hoffmann, W; Becher, R; Schmidt, C G; Bamberg, M; Quast, U; Haralambie, E; Linzenmeier, G

    1986-04-01

    In Essen 121 bone marrow transplantations were carried out. The indications were severe aplastic anemia, acute leukemia in relapse, acute leukemia in remission or chronic myeloid leukemia. The conditioning regimen consisted of cyclophosphamide or the combination of cyclophosphamide and total body irradiation. All patients were treated under strict gnotobiotic care. To mitigate the risk of CMV infections intravenous CMV-hyperimmunoglobulin and CMV-negative blood products have been applied routinely since two years. MTX was used as prophylaxis against GVH-disease. In case of severe aplastic anemia 13 patients (72%) are still alive with a median observation time of 24 months. In the prognostically unfavourable group of acute leukemia in relapse only one patient showed long term survival. In this patient leukemic relapse occurred six years after transplantation. The survival rate of AML patients grafted during the first remission is 55% with a median observation time of 40 months. For patients grafted in the first consecutive remission of ALL the survival rate is 42% with a maximal observation time of 29 months. Out of 37 patients grafted because of CML, eight were in an advanced stage of the disease. 13 patients are still alive, the maximal observation time is 37 months. The overall incidence of GVHD in patients at risk was 28% in aplastic anemia, 26% in AML, 9% in ALL and 63% in CML. In aplastic anemia no patient developed an interstitial pneumonia. In leukemia the risk of fatal interstitial pneumonia was 34%.

  7. Bone marrow transplantation in severe aplastic anemia and acute or chronic leukemia

    International Nuclear Information System (INIS)

    Schaefer, U.W.; Mahmoud, H.K.; Beelen, D.W.; Hoffmann, W.; Becher, R.; Schmidt, C.G.; Bamberg, M.; Quast, U.; Haralambie, E.; Linzenmeier, G.; Stollmann, B.; Grosse-Wilde, H.; Richter, H.J.; Hantschke, D.; Henneberg, K.; Luboldt, W.

    1986-01-01

    In Essen 121 bone marrow transplantations were carried out. The indications were severe aplastic anemia, acute leukemia in relapse, acute leukemia in remission or chronic myeloid leukemia. The conditioning regimen consisted of cyclophosphamide or the combination of cyclophosphamide and total body irradiation. All patients were treated under strict gnotobiotic care. To mitigate the risk of CMV infections intravenous CMV-hyperimmunoglobulin and CMV-negative blood products have been applied routinely since two years. MTX was used as prophylaxis against GVH-disease. In case of severe aplastic anemia 13 patients (72%) are still alive with a median observation time of 24 months. In the prognostically unfavourable group of acute leukemia in relapse only one patient showed long term survival. In this patient leukemic relapse occurred six years after transplantation. The survival rate of AML patients grafted during the first remission is 55% with a median observation time of 40 months. For patients grafted in the first consecutive remission of ALL the survival rate is 42% with a maximal observation time of 29 months. Out of 37 patients grafted because of CML, eight were in an advanced stage of the disease. 13 patients are still alive, the maximal observation time is 37 months. The overall incidence of GVHD in patients at risk was 28% in aplastic anemia, 26% in AML, 9% in ALL and 63% in CML. In aplastic anemia no patient developed an interstitial pneumonia. In leukemia the risk of fatal interstitial pneumonia was 34%. (orig.) [de

  8. Epidemiology of acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Pendergrass, T.W.

    1985-01-01

    Although the etiology of acute leukemia is largely unknown, some facets of the puzzle are becoming clarified. Recognition of important patterns in age-specific mortality rates has suggested that events early in life, perhaps even prenatally, may have an influence on developing leukemia in childhood. The racial differences evident in mortality, incidence, and immunologic subtype of ALL suggest either differences in exposures to certain factors or differences in responses to those factors by white children. Hereditary factors appear to play a role. Familial and hereditary conditions exist that have high incidences of acute leukemia. Chromosomal anomalies are common in these conditions. Viral infections may play a role by contributing to alteration in genetic material through incorporation of the viral genome. How that virus is dealt with after primary infection seems important. The presence of immunodeficiency may allow wider dissemination or enhanced replication of such viruses, thereby increasing the likelihood of cellular transformation to an abnormal cell. Proliferation of that malignant cell to a clone may depend on other cofactors. Perhaps prolonged exposure to substances like benzene or alkylating agents may enhance these interactions between virus and genetic material. Does this change DNA repair mechanisms. Are viral infections handled differently. Is viral genomic information more easily integrated into host cells. Ionizing radiation has multiple effects. Alteration in genetic material occurs both at the molecular and chromosomal levels. DNA may be altered, lost, or added in the cell's attempt to recover from the injury

  9. Morbidity associated to the transfusion support in pediatric patients with acute leukemia in the National Cancer Institute

    International Nuclear Information System (INIS)

    Vizcaino Valderrama, Martha; Suarez Mattos, Amaranto; Hernandez Kunzel, Jorge Alberto; Restrepo, Alexandra

    2002-01-01

    Acute leukemia represents the most common cancer in pediatrics. The current treatments made necessary a hematological support which increases the risks of complications, like fever, immunologic reaction, infections and, graft versus host disease. The objective of the present study was to determine the morbidity associated with transfusion support in pediatric patients with acute leukemia. In the pediatric population with diagnosis of acute leukemia in the INC during one and half year, the morbidity associated with transfusions was low and couldn't be related to the treatment given to the transfused products

  10. The Role of Hematopoietic Stem-Cell Transplantation in First Remission in Pediatric Acute Lymphoblastic Leukemia: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Neel S. Bhatt

    2017-05-01

    Full Text Available Context Survival after allogeneic hematopoietic stem-cell transplantation (HSCT for children with hematologic malignancies including acute lymphoblastic leukemia (ALL continues to improve in part due to advancement in HLA typing and enhanced supportive care. Despite improved outcomes with HSCT, the decision to offer it in first remission (CR1 in children with ALL remains a topic of debate and uncertainty. This review aims to discuss the role of HSCT in CR1 for children with high-risk subsets of ALL in the current era. Evidence Acquisition A thorough review of the literature was performed using electronic databases: PubMed, Google Scholar, and bibliographies. Studies focusing on high-risk subsets of ALL (Primary Induction Failure, Severe Hypodiploidy, Philadelphia-chromosome positive ALL, T-Cell ALL, Infant ALL, ALL with persistent minimal residual disease (MRD, and Philadelphia-like ALL were included. Publications in non- English language were excluded. Results Based on our review of the current literature, HSCT should be considered in first remission for patients with primary induction failure, severe hypodiploidy, T-cell ALL with poor response, high-risk infant ALL, and persistently positive MRD. In contrast, HSCT in CR1 may not be warranted for patients with early T-cell progenitor ALL or Philadelphia-chromosome positive ALL. Further data are needed to make specific recommendations regarding Philadelphia-like ALL. Conclusions As our understanding of high-risk leukemia biology continues to develop, the role of HSCT in ALL CR1 will need to be revisited.

  11. Identification of high-risk areas for harbour porpoise Phocoena phocoena bycatch using remote electronic monitoring and satellite telemetry data

    DEFF Research Database (Denmark)

    Kindt-Larsen, Lotte; Berg, Casper Willestofte; Tougaard, J.

    2016-01-01

    grounds, quantify fishing effort and document harbour porpoise bycatch. Movement data from 66 harbour porpoises equipped with satellite transmitters from 1997 to 2012 were used to model population density. A simple model was constructed to investigate the relationship between the response (number...... telemetry or REM data allow for identification of areas of potential high and low bycatch risk, and better predictions are obtained when combining the 2 sources of data. The final model can thus be used as a tool to identify areas of bycatch risk...... and lower risk of porpoise bycatch. From May 2010 to April 2011, 4 commercial gillnet vessels were equipped with remote electronic monitoring (REM) systems. The REM system recorded time, GPS position and closed-circuit television (CCTV) footage of all gillnet hauls. REM data were used to identify fishing...

  12. The Basel experience with total body irradiation for conditioning patients with acute leukemia for allogenic bone marrow transplantation

    International Nuclear Information System (INIS)

    Speck, B.; Cornu, P.; Nissen, C.; Gratwohl, A.; Sartorius, J.

    1979-01-01

    We are reporting our experience with 13 patients suffering from end stage acute leukemia that were prepared for allogeneic bone marrow transplantation by combined chemotherapy followed by high dose cyclophosphamide (Cy) and total body irradiation (TBI). Only one patient became a long term survivor. Of the evaluable 12 patients, 6 died of interstitial pneumonia, 4 of GvH and 1 of recurrent leukemia. We conclude that adding combined chemotherapy to the standard conditioning program with Cy and TBI probably increases the risk of developing fatal interstitial pneumonia without eliminating the risk of recurrent leukemia. We suggest that allogenic marrow grafts should be performed earlier in the course of refractory acute leukemias, because in patients with end stage disease its chances of being curative are small

  13. Outcome of acute lymphoblastic leukemia in children with down syndrome-Polish pediatric leukemia and lymphoma study group report.

    Science.gov (United States)

    Zawitkowska, Joanna; Odój, Teresa; Drabko, Katarzyna; Zaucha-Prażmo, Agnieszka; Rudnicka, Julia; Romiszewski, Michał; Matysiak, Michał; Kwiecińska, Kinga; Ćwiklińska, Magdalena; Balwierz, Walentyna; Owoc-Lempach, Joanna; Derwich, Katarzyna; Wachowiak, Jacek; Niedźwiecki, Maciej; Adamkiewicz-Drożyńska, Elżbieta; Trelińska, Joanna; Młynarski, Wojciech; Kołtan, Andrzej; Wysocki, Mariusz; Tomaszewska, Renata; Szczepański, Tomasz; Płonowski, Marcin; Krawczuk-Rybak, Maryna; Ociepa, Tomasz; Urasiński, Tomasz; Mizia-Malarz, Agnieszka; Sobol-Milejska, Grażyna; Karolczyk, Grażyna; Kowalczyk, Jerzy

    2017-05-01

    Children with Down syndrome (DS) have a 20-fold increased risk of developing leukemia compared with the general population. The aim of the study was to analyze the outcome of patients diagnosed with Down syndrome and acute lymphoblastic leukemia (ALL) in Poland between the years 2003 and 2010. A total of 1848 children were diagnosed with ALL (810 females and 1038 males). Of those, 41 (2.2%) had DS. The children were classified into three risk groups: a standard-risk group-14 patients, an intermediate-risk group-24, a high-risk group-3. All patients were treated according to ALLIC 2002 protocol. The median observation time of all patients was 6.1 years, and in patients with DS 5.3 years. Five-year overall survival (OS) was the same in all patients (86% vs 86%, long-rank test, p = .9). The relapse-free survival (RFS) was calculated as 73% in patients with DS and 81% in patients without DS during a median observation time (long-rank test, p = .3). No statistically significant differences were found in the incidence of nonrelapse mortality between those two groups of patients (p = .72). The study was based on children with ALL and Down syndrome who were treated with an identical therapy schedule as ALL patients without DS, according to risk group. This fact can increase the value of the presented results.

  14. Risk mitigation strategy for the ITER electron cyclotron upper port launcher

    NARCIS (Netherlands)

    Goede, A. P. H.; Bongers, W. A.; Elzendoorn, B. S. Q.; M. F. Graswinckel,; M.R. de Baar,

    2010-01-01

    A basic requirement for ITER equipment to meet is a high level of reliability, because ITER operation time is precious and radioactive operation leaves limited scope for repair. In order to reduce the risk of failure during ITER operation an effective risk mitigation strategy is necessary. This

  15. Low-dose total skin electron beam therapy for cutaneous lymphoma. Minimal risk of acute toxicities

    Energy Technology Data Exchange (ETDEWEB)

    Kroeger, Kai; Elsayad, Khaled; Moustakis, Christos; Haverkamp, Uwe; Eich, Hans Theodor [University Hospital of Muenster, Department of Radiation Oncology, Muenster (Germany)

    2017-12-15

    Low-dose total skin electron beam therapy (TSEBT) is attracting increased interest for the effective palliative treatment of primary cutaneous T-cell lymphoma (pCTCL). In this study, we compared toxicity profiles following various radiation doses. We reviewed the records of 60 patients who underwent TSEBT for pCTCL between 2000 and 2016 at the University Hospital of Munster. The treatment characteristics of the radiotherapy (RT) regimens and adverse events (AEs) were then analyzed and compared. In total, 67 courses of TSEBT were administered to 60 patients. Of these patients, 34 (51%) received a standard dose with a median surface dose of 30 Gy and 33 patients (49%) received a low dose with the median surface dose of 12 Gy (7 salvage low-dose TSEBT courses were administered to 5 patients). After a median follow-up of 15 months, the overall AE rate was 100%, including 38 patients (57%) with grade 2 and 7 (10%) with grade 3 AEs. Patients treated with low-dose TSEBT had significantly fewer grade 2 AEs than those with conventional dose regimens (33 vs. 79%, P < 0.001). A lower grade 3 AE rate was also observed in patients who had received the low-dose regimen compared to those with the conventional dose regimens (6 vs. 15%, P = 0.78). Multiple/salvage low-dose TSEBT courses were not associated with an increased risk of acute AEs. Low-dose TSEBT regimens are associated with significantly fewer grade 2 acute toxicities compared with conventional doses of TSEBT. Repeated/Salvage low-dose TSEBT, however, appears to be tolerable and can even be applied safely in patients with cutaneous relapses. (orig.) [German] Eine niedrigdosierte Ganzhautelektronenbestrahlung (TSEBT) wird vermehrt zur effektiven palliativen Behandlung von Patienten mit primaer kutanen T-Zell-Lymphomen (pCTCL) eingesetzt. In dieser Studie vergleichen wir die Toxizitaetsprofile verschiedener Dosiskonzepte. Untersucht wurden 60 zwischen 2000 und 2016 am Universitaetsklinikum Muenster mittels TSEBT

  16. Prospective neurodevelopmental studies of two children treated with total body irradiation and bone marrow transplantation for acute leukemia in infancy

    International Nuclear Information System (INIS)

    Kaleita, T.; Tesler, A.; Feig, S.A.

    1987-01-01

    Five-year neurodevelopmental studies of two infants with acute leukemia are presented. Both patients underwent bone marrow transplantation (BMT) after conditioning with cyclophosphamide and total body irradiation (TBI). Neither patient was treated with intrathecal chemotherapy. Their outcome is remarkable for normal development of intelligence, language, perception, and motor coordination. These results suggest that TBI and BMT should be considered in future therapeutic studies of infants with acute leukemia, who are at great risk for failure of conventional therapy

  17. Treatment of Aggressive NK-Cell Leukemia

    DEFF Research Database (Denmark)

    Boysen, Anders Kindberg; Jensen, Paw; Johansen, Preben

    2011-01-01

    Aggressive NK-cell leukemia is a rare malignancy with neoplastic proliferation of natural killer cells. It often presents with constitutional symptoms, a rapid declining clinical course, and a poor prognosis with a median survival of a few months. The disease is usually resistant to cytotoxic...... literature concerning treatment of aggressive NK-cell leukemia....

  18. The Danish National Chronic Lymphocytic Leukemia Registry

    DEFF Research Database (Denmark)

    da Cunha-Bang, Caspar; Geisler, Christian Hartmann; Enggaard, Lisbeth

    2016-01-01

    AIM: In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL) in Denmark. Secondarily, to evaluate...

  19. The discovery and early understanding of leukemia

    NARCIS (Netherlands)

    Kampen, Kim R.

    The early history of leukemia reaches back 200 years. In 1811, Peter Cullen defined a case of splenitis acutus with unexplainable milky blood. Alfred Velpeau defined the leukemia associated symptoms, and observed pus in the blood vessels (1825). Alfred Donne detected a maturation arrest of the white

  20. Esterase reactions in acute myelomonocytic leukemia.

    Science.gov (United States)

    Kass, L

    1977-05-01

    Specific and nonspecific esterase reactions of bone marrow cells from 14 patients with untreated acute myelomonocytic leukemia and six patients with acute histiomonocytic leukemia were examined. The technic for esterase determination permitted simultaneous visualization of both esterases on the same glass coverslip containing the marrow cells. In cases of acute histiomonocytic leukemia, monocytes, monocytoid hemohistioblasts and undifferentiated blasts stained intensely positive for nonspecific esterase, using alpha-naphthyl acetate as the substrate. No evidence of specific esterase activity using naphthol ASD-chloroacetate as the substrate and fast blue BBN as the dye coupler was apparent in these cells. In all of the cases of acute myelomonocytic leukemia, both specific and nonspecific esterases were visualized within monocytes, monocytoid cells, and granulocytic cells that had monocytoid-type nuclei. Nonspecific esterase activity was not observed in polymorphonuclear leukocytes in cases of myelomonocytic leukemia. The results support a current viewpoint that acute myelomonocytic leukemia may be a variant of acute myeloblastic leukemia, and that cytochemically, many of the leukemic cells in myelomonocytic leukemia share properties of both granulocytes and monocytes.

  1. Genetics Home Reference: chronic myeloid leukemia

    Science.gov (United States)

    ... Central Quintás-Cardama A, Cortes JE. Chronic myeloid leukemia: diagnosis and treatment. Mayo Clin Proc. 2006 Jul;81(7):973-88. Review. Citation on PubMed Skorski T. Genetic mechanisms of chronic myeloid leukemia blastic transformation. Curr Hematol Malig Rep. 2012 Jun; ...

  2. Chronic Myelogenous Leukemia (CML) (For Parents)

    Science.gov (United States)

    ... studying the leukemia cells collected from the blood, bone marrow, and/or spinal fluid, doctors can determine the type of leukemia a child has. This is important because treatment varies among different types ... blood or bone marrow, doctors can tell whether the Philadelphia chromosome is ...

  3. Dose-response relationship of leukemia incidence among atomic bomb survivors and their controls by absorbed marrow dose and two types of leukemia Hiroshima and Nagasaki, October 1950 - December 1978

    International Nuclear Information System (INIS)

    Ishimaru, Toranosuke; Otake, Masanori; Ichimaru, Michito; Mikami, Motoko.

    1982-07-01

    Analysis of the relationship of the incidence of leukemia to gamma and neutron dose among atomic bomb survivors until 1971 has been reported previously by RERF. The present inquiry was prompted by the extension of case finding to 1978 and by the recent availability of new dose estimates for this fixed cohort. It is focused on the relationship of absorbed marrow dose of gamma rays and neutrons to the incidence of two types of leukemia in the fixed cohort of A-bomb survivors and their controls, the Life Span Study extended sample, in the period October 1950-December 1978. Three dose-response models have been fitted to the data on acute leukemia and chronic granulocytic leukemia. The relationship of the incidence of acute leukemia to gamma and neutron dose again suggests that the ''best'' fitting model involves a dependence on the square of the gamma dose and a linear dependence on neutrons. The estimated relative biological effectiveness (RBE) of neutrons in the induction of acute leukemia is approximately 44/√Dn(Dn = neutron dose) under this model. Based on the 95% confidence limits of the estimated RBE, the risk of this disease is estimated as 0.0026 - 0.0072 cases per million person-years per rem 2 of marrow dose. This analysis has failed, however, to produce a significant dose-response function for the incidence of chronic granulocytic leukemia in relation to the two kinds of radiation. (author)

  4. Perceptions of the risk of child abduction or loss and the utility of child electronic security devices.

    Science.gov (United States)

    Dixon, R M; Pasnak, R

    1997-09-01

    Perceptions of the susceptibility of young children to becoming lost or being abducted, and of the potential usefulness of child electronic security devices, were examined via a questionnaire. Data were provided by 41 volunteers, most of them from a local government office centre. The questionnaire asked for demographic data, and then for the risk of a child being abducted or lost when under the supervision of different caregivers and in different situations. The probable effectiveness of three common abductor ploys was also addressed. The questionnaire concluded with 10 questions about child electronic security devices. Respondents viewed mothers, fathers, and grandparents as equally responsible caregivers and young adults/babysitters as the least responsible. These effects diminished as the age of the children increased. The garden at home was judged to be the most secure environment for children of all ages, while an amusement park was judged the least secure environment. Children were perceived to be more at risk of an abduction when a stranger asked for physical assistance or to take them to the hospital because their parents were hurt, than when asked for directions. Furthermore, the respondents expressed a moderately strong need for child electronic security devices, and viewed parents who use them as more responsible than those who do not.

  5. Addition of Arsenic Trioxide into Induction Regimens Could Not Accelerate Recovery of Abnormality of Coagulation and Fibrinolysis in Patients with Acute Promyelocytic Leukemia.

    Directory of Open Access Journals (Sweden)

    Ye Zhang

    Full Text Available All-trans retinoic acid combined to anthracycline-based chemotherapy is the standard regimen of acute promyelocytic leukemia. The advent of arsenic trioxide has contributed to improve the anti-leukemic efficacy in acute promyelocytic leukemia. The objectives of the current study were to evaluate if dual induction by all-trans retinoic acid and arsenic trioxide could accelerate the recovery of abnormality of coagulation and fibrinolysis in patients with acute promyelocytic leukemia.Retrospective analysis was performed in 103 newly-diagnosed patients with acute promyelocytic leukemia. Hemostatic variables and the consumption of component blood were comparably analyzed among patients treated by different induction regimen with or without arsenic trioxide.Compared to patients with other subtypes of de novo acute myeloid leukemia, patients with acute promyelocytic leukemia had lower platelet counts and fibrinogen levels, significantly prolonged prothrombin time and elevated D-dimers (P<0.001. Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification presented lower initial fibrinogen level than that of low-risk group (P<0.05. After induction treatment, abnormal coagulation and fibrinolysis of patients with acute promyelocytic leukemia was significantly improved before day 10. The recovery of abnormal hemostatic variables (platelet, prothrombin time, fibrinogen and D-dimer was not significantly accelerated after adding arsenic trioxide in induction regimens; and the consumption of transfused component blood (platelet and plasma did not dramatically change either. Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification had higher platelet transfusion demands than that of low-risk group (P<0.05.Unexpectedly, adding arsenic trioxide could not accelerate the recovery of abnormality of coagulation and fibrinolysis in acute promyelocytic leukemia patients who received all

  6. Predicting Sepsis Risk Using the "Sniffer" Algorithm in the Electronic Medical Record.

    Science.gov (United States)

    Olenick, Evelyn M; Zimbro, Kathie S; DʼLima, Gabrielle M; Ver Schneider, Patricia; Jones, Danielle

    The Sepsis "Sniffer" Algorithm (SSA) has merit as a digital sepsis alert but should be considered an adjunct to versus an alternative for the Nurse Screening Tool (NST), given lower specificity and positive predictive value. The SSA reduced the risk of incorrectly categorizing patients at low risk for sepsis, detected sepsis high risk in half the time, and reduced redundant NST screens by 70% and manual screening hours by 64% to 72%. Preserving nurse hours expended on manual sepsis alerts may translate into time directed toward other patient priorities.

  7. Origin of specific chromosome aberration in radiation-induced leukemia

    International Nuclear Information System (INIS)

    Ban, Nobuhiko; Kai, Michiaki; Masuno, Yoko

    2005-01-01

    The theme in the title is discussed from the four aspects of specific chromosome aberration (sAb) patterns in radiation-induced leukemia (RIL), possibility for radiation to induce the sAb in RIL, any evidence for participation of delayed aberration to form sAb and the proportion of such healthy humans as having the specifically rearranged genome. Data of sAb observed in leukemia of 25 A-bomb survivors and of 38 patients post radiotherapy of cancers give a rather common pattern. However, many inconsistent results are obtained for sAb in patients post radiotherapy, A-bomb survivors, residents living in radio-contaminated houses in Taipei, in vitro exposure, and Chernobyl residents. At present, any clear evidence is available neither for sAb derived from the delayed aberration nor for estimating the proportion with the specifically rearranged gene. As above, it is unlikely that radiation induces such a translocation abnormality as BCR-ABL specifically seen in leukemia, and this aspect will be important for studies on the genesis of RIL and its risk assessment. (S.I.)

  8. Population prevalence and control of cardiovascular risk factors: What electronic medical records tell us

    Directory of Open Access Journals (Sweden)

    Arantxa Catalán-Ramos

    2014-01-01

    Conclusions: Hypertension was the most prevalent cardiovascular risk factor in the Catalan population attended at primary care centers. About two thirds of individuals with hypertension or DM2 were adequately controlled; hypercholesterolemia control was particularly low.

  9. Electronic Health Record-Enabled Big-Data Approaches to Nephrotoxin-Associated Acute Kidney Injury Risk Prediction.

    Science.gov (United States)

    Sutherland, Scott M

    2018-06-09

    Nephrotoxin-associated acute kidney injury (NTx-AKI) has become one of the most common causes of AKI among hospitalized adults and children; across acute and intensive care populations, exposure to nephrotoxins accounts for 15-25% of AKI. Although some interventions have shown promise in observational studies, no treatments currently exist for NTx-AKI once it occurs. Thus, nearly all effective strategies are aimed at prevention. The primary obstacle to prevention is risk prediction and the determination of which patients are more likely to develop NTx-AKI when exposed to medications with nephrotoxic potential. Historically, traditional statistical modeling has been applied to previously recognized clinical risk factors to identify predictors of NTx-AKI. However, increased electronic health record adoption and the evolution of "big-data" approaches to predictive analytics may offer a unique opportunity to prevent NTx-AKI events. This article describes prior and current approaches to NTx-AKI prediction and offers three novel use cases for electronic health record-enabled NTx-AKI forecasting and risk profiling. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. [Acute lymphoblastic leukemia: a genomic perspective].

    Science.gov (United States)

    Jiménez-Morales, Silvia; Hidalgo-Miranda, Alfredo; Ramírez-Bello, Julián

    In parallel to the human genome sequencing project, several technological platforms have been developed that let us gain insight into the genome structure of human entities, as well as evaluate their usefulness in the clinical approach of the patient. Thus, in acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, genomic tools promise to be useful to detect patients at high risk of relapse, either at diagnosis or during treatment (minimal residual disease), and they also increase the possibility to identify cases at risk of adverse reactions to chemotherapy. Therefore, the physician could offer patient-tailored therapeutic schemes. A clear example of the useful genomic tools is the identification of single nucleotide polymorphisms (SNPs) in the thiopurine methyl transferase (TPMT) gene, where the presence of two null alleles (homozygous or compound heterozygous) indicates the need to reduce the dose of mercaptopurine by up to 90% to avoid toxic effects which could lead to the death of the patient. In this review, we provide an overview of the genomic perspective of ALL, describing some strategies that contribute to the identification of biomarkers with potential clinical application. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  11. The use and risk of portable electronic devices while cycling among different age groups.

    NARCIS (Netherlands)

    Goldenbeld, C. Houtenbos, M. Ehlers, E. & Waard, D. de

    2012-01-01

    In The Netherlands, a survey was set up to monitor the extent of the use of portable, electronic devices while cycling amongst different age groups of cyclists and to estimate the possible consequences for safety. The main research questions concerned age differences in the self-reported use of

  12. The use and risk of portable electronic devices while cycling among different age groups

    NARCIS (Netherlands)

    Goldenbeld, C.; Houtenbos, M.; Ehlers, E.; De Waard, D.

    Introduction: In the Netherlands, a survey was set up to monitor the extent of the use of portable, electronic devices while cycling amongst different age groups of cyclists and to estimate the possible consequences for safety. Method: The main research questions concerned age differences in the

  13. RESULTS OF HEMATOPOIETIC CELL TRANSPLANTATION IN PEDIATRIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    A. Mousavi

    2008-05-01

    Full Text Available Hematopoietic cell transplantation (HCT is an accepted treatment for acute myeloid leukemia (AML in first remission, the treatment of choice for chronic myeloid leukemia (CML and high risk groups of ALL who relapse with conventional chemotherapy. We assessed results of HCT for pediatric leukemia in our center. A total of 92 children, 63 with diagnose of AML, 23 with ALL and 6 with CML received allogeneic transplantation from HLA full matched siblings (57.6% and autologous transplantation (42.4%. Source of hematopoietic cells were peripheral blood 83.7%, bone marrow 15.2% and cord blood 1.6%. The median transplanted nucleated cells were 6.4 ± 4.7 ×108 /Kg (body weight of patients and mononuclear cells were 5.5 ± 2.9×108/Kg. The most common conditioning regimens were cyclophosphamide + busulfan. Prophylaxis regimen for GVHD was cyclosporin ± methotrexate. GVHD occurred in 50 (54.3% patients. Eighty five of children had engraftment, 26 (28.6% relapsed and 57 (62% are alive. The most common cause of death was relapse (68.6%. Five years overall survival of patients with AML and ALL were 49% and 44% respectively and disease free survival of them were 52% and 49%. One year overall survival and disease free survival of CML was 57%. Overall survival increased with increasing age of patients at transplantation time (P = 0.06. Longer survival significantly related to earlier WBC and platelet recovery (P < 0.0001 and P = 0.006 respectively. Considering acceptable overall and disease free survival of patients after HCT, we concluded that is a good modality in treatment of leukemia of children.

  14. Cytogenetic, clinical, and cytologic characteristics of radiotherapy-related leukemias

    International Nuclear Information System (INIS)

    Philip, P.; Pedersen-Bjergaard, J.

    1988-01-01

    From 1978 to 1985, we observed eight cases of acute nonlymphocytic leukemia or preleukemia, three cases of acute lymphoblastic leukemia, and three cases of chronic myeloid leukemia in patients previously treated exclusively with radiotherapy for other tumor types. The latent period from administration of radiotherapy to development of leukemia varied between 12 and 243 months. Clonal chromosome aberrations reported previously as characteristic of acute nonlymphocytic leukemia following therapy with alkylating agents were observed in three of the eight patients with acute nonlymphocytic leukemia (5q- and -7) and in two of the three patients with acute lymphoblastic leukemia (-7 and 12p-). All three patients with radiotherapy-related chronic myeloid leukemia presented a t(9;22)(q34;q11). The results suggest that cytogenetic characteristics may reflect the etiology in radiation-induced acute leukemias, whereas radiation-related chronic myeloid leukemia does not seem to differ chromosomally from de novo cases of the disease

  15. Fetal Growth and Childhood Acute Lymphoblastic Leukemia: Findings from the Childhood Leukemia International Consortium (CLIC)

    Science.gov (United States)

    Milne, Elizabeth; Greenop, Kathryn R.; Metayer, Catherine; Schüz, Joachim; Petridou, Eleni; Pombo-de-Oliveira, Maria S.; Infante-Rivard, Claire; Roman, Eve; Dockerty, John D.; Spector, Logan G.; Koifman, Sérgio; Orsi, Laurent; Rudant, Jérémie; Dessypris, Nick; Simpson, Jill; Lightfoot, Tracy; Kaatsch, Peter; Baka, Margarita; Faro, Alessandra; Armstrong, Bruce K.; Clavel, Jacqueline; Buffler, Patricia A.

    2013-01-01

    Positive associations have been reported between measures of accelerated fetal growth and risk of childhood acute lymphoblastic leukemia (ALL). We investigated this association by pooling individual-level data from 12 case-control studies participating in the Childhood Leukemia International Consortium. Two measures of fetal growth – weight-for-gestational-age and proportion of optimal birth weight (POBW) – were analysed. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, and combined in fixed effects meta-analyses. Pooled analyses of all data were also undertaken using multivariable logistic regression. Subgroup analyses were undertaken when possible. Data on weight for gestational age were available for 7,348 cases and 12,489 controls from all 12 studies and POBW data were available for 1,680 cases and 3,139 controls from three studies. The summary ORs from the meta-analyses were 1.24 (95% CI 1.13, 1.36) for children who were large for gestational age relative to appropriate for gestational age, and 1.16 (95% CI: 1.09, 1.24) for a one standard deviation increase in POBW. The pooled analyses produced similar results. The summary and pooled ORs for small-for-gestational-age children were 0.83 (95% CI: 0.75, 0.92) and 0.86 (95% CI 0.77, 0.95) respectively. Results were consistent across subgroups defined by sex, ethnicity and immunophenotype, and when the analysis was restricted to children who did not have high birth weight. The evidence that accelerated fetal growth is associated with a modest increased risk of childhood ALL is strong and consistent with known biological mechanisms involving insulin like growth factors. PMID:23754574

  16. Rhabdomyosarcoma presenting as acute leukemia.

    Science.gov (United States)

    Morandi, S; Manna, A; Sabattini, E; Porcellini, A

    1996-08-01

    We describe a case of a very unusual presentation of rhabdomyosarcoma. An 18-year-old woman presented with symptoms and signs compatible with acute leukemia. The bone marrow picture showed diffuse involvement sustained by undifferentiated blasts that turned out to be of striated muscle origin by immunochemistry. While it is well known that rhabdomyosarcoma may metastasize to the bone marrow, extensive marrow involvement with leukemic spread as a unique clinical manifestation is extremely rare. Our observation further confirms the need to consider rhabdomyosarcoma among the possible differential diagnoses in patients who present with a leukemic picture and atypical blasts lacking all hematopoietic markers.

  17. Hairy cell leukemia-variant

    International Nuclear Information System (INIS)

    Quadri, Mohammad I.; Al-Sheikh, Iman H.

    2001-01-01

    Hairy cell leukaemia variant is a very rare chronic lymphoproliferative disorder and is closely related to hairy cell leukemia. We hereby describe a case of hairy cell leukaemia variant for the first time in Saudi Arabia. An elderly Saudi man presented with pallor, massive splenomegaly, and moderate hepatomegaly. Hemoglobin was 7.7 g/dl, Platelets were 134 x109/l and white blood count was 140x10 9/l with 97% being abnormal lymphoid cells with cytoplasmic projections. The morphology, cytochemistry, and immunophenotype of the lymphoid cells were classical of hairy cell leukaemia variant. The bone marrow was easily aspirated and findings were consistent with hairy cell leukaemia variant. (author)

  18. Leukemia in humans following exposure to ionizing radiation. A summary of the findings in Hiroshima and Nagasaki and comparison with other human experience

    Energy Technology Data Exchange (ETDEWEB)

    Brill, A B; Tomonaga, Masanobu; Heyssel, R M

    1960-10-01

    A review of the Hiroshima-Nagasaki leukemia experience thirteen years after the atomic bomb explosion in those two cities, and comparisons with other collected series of leukemia cases following radiation has again demonstrated beyond reasonable doubt the leukemogenic effect of ionizing radiation on humans. In spite of the heterogeneity of the various study groups there are surprisingly consistent findings. An increased risk of leukemia following doses probably as low as 50 to 100 rads (air-entry dose) whole body radiation has been demonstrated. Above this dose the increase in incidence of leukemia may be related linearly to dose of radiation. When extrapolated to zero dose this line intersects the expected spontaneous incidence. In the lower range it is impossible to be certain regarding the presence or absence of a threshold. As in other series the acute lymphocytic variety of leukemia in the very young is most increased. Chronic granulocytic leukemia was seen most commonly among the Japanese in the older age groups. The predilection of the various types of leukemia for specific age groups does not appear to be markedly altered although possibly the incidence of chronic granulocytic leukemia has been shifted to younger ages. Males and children in the age group below ten appear to be most sensitive to induction of leukemia by irradiation. The increased occurrenc of leukemia in an irradiated population appears to start about eighteen months after the event. In Japan the increased risk has persisted for thirteen years with the time of maximum risk approximately four to eight years following radiation. 128 references, 2 figures, 14 tables.

  19. Predicting Readmission at Early Hospitalization Using Electronic Clinical Data: An Early Readmission Risk Score.

    Science.gov (United States)

    Tabak, Ying P; Sun, Xiaowu; Nunez, Carlos M; Gupta, Vikas; Johannes, Richard S

    2017-03-01

    Identifying patients at high risk for readmission early during hospitalization may aid efforts in reducing readmissions. We sought to develop an early readmission risk predictive model using automated clinical data available at hospital admission. We developed an early readmission risk model using a derivation cohort and validated the model with a validation cohort. We used a published Acute Laboratory Risk of Mortality Score as an aggregated measure of clinical severity at admission and the number of hospital discharges in the previous 90 days as a measure of disease progression. We then evaluated the administrative data-enhanced model by adding principal and secondary diagnoses and other variables. We examined the c-statistic change when additional variables were added to the model. There were 1,195,640 adult discharges from 70 hospitals with 39.8% male and the median age of 63 years (first and third quartile: 43, 78). The 30-day readmission rate was 11.9% (n=142,211). The early readmission model yielded a graded relationship of readmission and the Acute Laboratory Risk of Mortality Score and the number of previous discharges within 90 days. The model c-statistic was 0.697 with good calibration. When administrative variables were added to the model, the c-statistic increased to 0.722. Automated clinical data can generate a readmission risk score early at hospitalization with fair discrimination. It may have applied value to aid early care transition. Adding administrative data increases predictive accuracy. The administrative data-enhanced model may be used for hospital comparison and outcome research.

  20. Risk Factors for Gambling Problems on Online Electronic Gaming Machines, Race Betting and Sports Betting.

    Science.gov (United States)

    Hing, Nerilee; Russell, Alex M; Browne, Matthew

    2017-01-01

    Growth of Internet gambling has fuelled concerns about its contribution to gambling problems. However, most online gamblers also gamble on land-based forms, which may be the source of problems for some. Studies therefore need to identify the problematic mode of gambling (online or offline) to identify those with an online gambling problem. Identifying most problematic form of online gambling (e.g., EGMs, race betting, sports betting) would also enable a more accurate examination of gambling problems attributable to a specific online gambling form. This study pursued this approach, aiming to: (1) determine demographic, behavioral and psychological risk factors for gambling problems on online EGMs, online sports betting and online race betting; (2) compare the characteristics of problematic online gamblers on each of these online forms. An online survey of 4,594 Australian gamblers measured gambling behavior, most problematic mode and form of gambling, gambling attitudes, psychological distress, substance use, help-seeking, demographics and problem gambling status. Problem/moderate risk gamblers nominating an online mode of gambling as their most problematic, and identifying EGMs ( n = 98), race betting ( n = 291) or sports betting ( n = 181) as their most problematic gambling form, were compared to non-problem/low risk gamblers who had gambled online on these forms in the previous 12 months ( n = 64, 1145 and 1213 respectively), using bivariate analyses and then logistic regressions. Problem/moderate risk gamblers on each of these online forms were then compared. Risk factors for online EGM gambling were: more frequent play on online EGMs, substance use when gambling, and higher psychological distress. Risk factors for online sports betting were being male, younger, lower income, born outside of Australia, speaking a language other than English, more frequent sports betting, higher psychological distress, and more negative attitudes toward gambling. Risk factors for

  1. Risk Factors for Gambling Problems on Online Electronic Gaming Machines, Race Betting and Sports Betting

    Directory of Open Access Journals (Sweden)

    Nerilee Hing

    2017-05-01

    Full Text Available Growth of Internet gambling has fuelled concerns about its contribution to gambling problems. However, most online gamblers also gamble on land-based forms, which may be the source of problems for some. Studies therefore need to identify the problematic mode of gambling (online or offline to identify those with an online gambling problem. Identifying most problematic form of online gambling (e.g., EGMs, race betting, sports betting would also enable a more accurate examination of gambling problems attributable to a specific online gambling form. This study pursued this approach, aiming to: (1 determine demographic, behavioral and psychological risk factors for gambling problems on online EGMs, online sports betting and online race betting; (2 compare the characteristics of problematic online gamblers on each of these online forms. An online survey of 4,594 Australian gamblers measured gambling behavior, most problematic mode and form of gambling, gambling attitudes, psychological distress, substance use, help-seeking, demographics and problem gambling status. Problem/moderate risk gamblers nominating an online mode of gambling as their most problematic, and identifying EGMs (n = 98, race betting (n = 291 or sports betting (n = 181 as their most problematic gambling form, were compared to non-problem/low risk gamblers who had gambled online on these forms in the previous 12 months (n = 64, 1145 and 1213 respectively, using bivariate analyses and then logistic regressions. Problem/moderate risk gamblers on each of these online forms were then compared. Risk factors for online EGM gambling were: more frequent play on online EGMs, substance use when gambling, and higher psychological distress. Risk factors for online sports betting were being male, younger, lower income, born outside of Australia, speaking a language other than English, more frequent sports betting, higher psychological distress, and more negative attitudes toward gambling. Risk

  2. Identifying risk factors for healthcare-associated infections from electronic medical record home address data

    Directory of Open Access Journals (Sweden)

    Rosenman Marc B

    2010-09-01

    Full Text Available Abstract Background Residential address is a common element in patient electronic medical records. Guidelines from the U.S. Centers for Disease Control and Prevention specify that residence in a nursing home, skilled nursing facility, or hospice within a year prior to a positive culture date is among the criteria for differentiating healthcare-acquired from community-acquired methicillin-resistant Staphylococcus aureus (MRSA infections. Residential addresses may be useful for identifying patients residing in healthcare-associated settings, but methods for categorizing residence type based on electronic medical records have not been widely documented. The aim of this study was to develop a process to assist in differentiating healthcare-associated from community-associated MRSA infections by analyzing patient addresses to determine if residence reported at the time of positive culture was associated with a healthcare facility or other institutional location. Results We identified 1,232 of the patients (8.24% of the sample with positive cultures as probable cases of healthcare-associated MRSA based on residential addresses contained in electronic medical records. Combining manual review with linking to institutional address databases improved geocoding rates from 11,870 records (79.37% to 12,549 records (83.91%. Standardization of patient home address through geocoding increased the number of matches to institutional facilities from 545 (3.64% to 1,379 (9.22%. Conclusions Linking patient home address data from electronic medical records to institutional residential databases provides useful information for epidemiologic researchers, infection control practitioners, and clinicians. This information, coupled with other clinical and laboratory data, can be used to inform differentiation of healthcare-acquired from community-acquired infections. The process presented should be extensible with little or no added data costs.

  3. Differential effects of atomic bomb irradiation in inducing major leukemia types

    International Nuclear Information System (INIS)

    Tomonaga, Masao; Matsuo, Tatsuki; Carter, R.L.

    1993-05-01

    In this report we utilize data from the additional 517 cases from the leukemia registry together with the Life Span Study (LSS) cohort data to study the effects of atomic bomb irradiation on major leukemia types. The French-American-British classification and other improved diagnostic methods were used to reclassify cases into 21 categories, including new disease entities such as adult T-cell leukemia (ATL). These categories were then grouped into four major types for analysis: (1) acute lymphocytic leukemia (ALL), (2) acute myeloid leukemia (AML) including myelodysplastic syndromes (MDS), (3) chronic myeloid leukemia (CML), and (4) OTHER types including ATL. Analyses of radiation effects were based on the updated Dosimetry System 1986(DS86). Incidence rates of all four leukemia types increased with increasing exposure level. The effects of radiation were significantly greater on the incidence of ALL and CML than on that of AML and OTHER. In the two lowest dose categories (1-49 and 50-499 mGy), estimated incidence either remained constant or increased slightly as the population of survivors aged. In the two highest dose categories (500-1,499 and ≥ 1,500 mGy). Among unexposed persons, the estimated risk of CML in Nagasaki relative to Hiroshima was significantly less than that of AML, whereas that of OTHER types was significantly greater. The time to onset of ALL, AML, and CML declined with increasing dose. The rate of decline, however, was greater for ALL and CML than for AML. The resulting differences at high doses reflect shorter incubation times for atomic-bomb-induced ALL and CML than for AML. (J.P.N.)

  4. Racial/ethnic differences in electronic cigarette knowledge, social norms, and risk perceptions among current and former smokers.

    Science.gov (United States)

    Webb Hooper, Monica; Kolar, Stephanie K

    2017-04-01

    Psychosocial factors that may affect electronic cigarette (e-cigarette) initiation or maintenance among racial/ethnic minorities are not well-understood. This study examined racial/ethnic differences in e-cigarette knowledge, risk perceptions, and social norms among current and former smokers. Individuals with a tobacco smoking history and an awareness of e-cigarettes (N=285) were recruited from the community from June to August 2014. Telephone-administered surveys assessed demographics, smoking status, and e-cigarette knowledge, risk perceptions, and normative beliefs. Analyses of covariance and multinomial logistic regression tested associations by race/ethnicity. Controlling for sociodemographics and smoking status, White participants scored significantly higher on e-cigarette knowledge, compared to both Hispanics and African Americans/Blacks. Knowledge was lower among African Americans/Blacks compared to Hispanics. Compared to both Whites and Hispanics, African American/Black participants held lower perceptions regarding e-cigarette health risks and were less likely to view e-cigarettes as addictive. Normative beliefs did not differ by race/ethnicity. In conclusion, e-cigarette knowledge, health risk perceptions, and perceived addictiveness differed by race/ethnicity. The variation in e-cigarette knowledge and beliefs among smokers and former smokers has implications for use, and potentially, dual use. Understanding these relationships in unrepresented populations can inform future research and practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Development of an Electronic Medical Record Based Alert for Risk of HIV Treatment Failure in a Low-Resource Setting

    Science.gov (United States)

    Puttkammer, Nancy; Zeliadt, Steven; Balan, Jean Gabriel; Baseman, Janet; Destiné, Rodney; Domerçant, Jean Wysler; France, Garilus; Hyppolite, Nathaelf; Pelletier, Valérie; Raphael, Nernst Atwood; Sherr, Kenneth; Yuhas, Krista; Barnhart, Scott

    2014-01-01

    Background The adoption of electronic medical record systems in resource-limited settings can help clinicians monitor patients' adherence to HIV antiretroviral therapy (ART) and identify patients at risk of future ART failure, allowing resources to be targeted to those most at risk. Methods Among adult patients enrolled on ART from 2005–2013 at two large, public-sector hospitals in Haiti, ART failure was assessed after 6–12 months on treatment, based on the World Health Organization's immunologic and clinical criteria. We identified models for predicting ART failure based on ART adherence measures and other patient characteristics. We assessed performance of candidate models using area under the receiver operating curve, and validated results using a randomly-split data sample. The selected prediction model was used to generate a risk score, and its ability to differentiate ART failure risk over a 42-month follow-up period was tested using stratified Kaplan Meier survival curves. Results Among 923 patients with CD4 results available during the period 6–12 months after ART initiation, 196 (21.2%) met ART failure criteria. The pharmacy-based proportion of days covered (PDC) measure performed best among five possible ART adherence measures at predicting ART failure. Average PDC during the first 6 months on ART was 79.0% among cases of ART failure and 88.6% among cases of non-failure (pART initiation were added to PDC, the risk score differentiated between those who did and did not meet failure criteria over 42 months following ART initiation. Conclusions Pharmacy data are most useful for new ART adherence alerts within iSanté. Such alerts offer potential to help clinicians identify patients at high risk of ART failure so that they can be targeted with adherence support interventions, before ART failure occurs. PMID:25390044

  6. Development of an electronic medical record based alert for risk of HIV treatment failure in a low-resource setting.

    Directory of Open Access Journals (Sweden)

    Nancy Puttkammer

    Full Text Available The adoption of electronic medical record systems in resource-limited settings can help clinicians monitor patients' adherence to HIV antiretroviral therapy (ART and identify patients at risk of future ART failure, allowing resources to be targeted to those most at risk.Among adult patients enrolled on ART from 2005-2013 at two large, public-sector hospitals in Haiti, ART failure was assessed after 6-12 months on treatment, based on the World Health Organization's immunologic and clinical criteria. We identified models for predicting ART failure based on ART adherence measures and other patient characteristics. We assessed performance of candidate models using area under the receiver operating curve, and validated results using a randomly-split data sample. The selected prediction model was used to generate a risk score, and its ability to differentiate ART failure risk over a 42-month follow-up period was tested using stratified Kaplan Meier survival curves.Among 923 patients with CD4 results available during the period 6-12 months after ART initiation, 196 (21.2% met ART failure criteria. The pharmacy-based proportion of days covered (PDC measure performed best among five possible ART adherence measures at predicting ART failure. Average PDC during the first 6 months on ART was 79.0% among cases of ART failure and 88.6% among cases of non-failure (p<0.01. When additional information including sex, baseline CD4, and duration of enrollment in HIV care prior to ART initiation were added to PDC, the risk score differentiated between those who did and did not meet failure criteria over 42 months following ART initiation.Pharmacy data are most useful for new ART adherence alerts within iSanté. Such alerts offer potential to help clinicians identify patients at high risk of ART failure so that they can be targeted with adherence support interventions, before ART failure occurs.

  7. Radiotherapy for leukemia in children, (1)

    International Nuclear Information System (INIS)

    Miyazaki, Toru; Konishi, Kiyosaburo; Sato, Noriko; Fujiwara, Fumihiro

    1983-01-01

    Following the development of effective chemotherapy for producing remissions of acute lymphocytic leukemia (ALL), a new phenomenon has emerged in this disease--central nervous system (CNS) leukemia. CNS leukemia has become an increasingly frequent obstacle to prolongation of initial complete remission. Prophylactic irradiation of the CNS concomitant with intrathecal administration of methotrexate (IT-MTX) has proved to be effective in the reduction of CNS involvement. The purpose of this paper is to describe the results of irradiation for prevention of CNS leukemia and to discuss their implications. The patients consisted of 32 children with acute leukemia, admitted to MAIZURU National Hospital from 1966 to 1980; 22 patients of them had ALL, the others ANLL (acute non-lymphocytic leukemia). Preventive CNS therapy was started in 1974, (group A), but there was no prevention before 1974 (group B). 1. In group B, six patients was treated by therapeutic cranial irradiation, but all cases resulted in death. 2. In group A, seven patients was treated by prophylactic cranial irradiation combined with IT-MTX, and all of them have been alive without CNS relapse for 2 to 4 2/3 years after therapy. 3. In group A, none of 7 patients (0 %) relapsed CNS leukemia initially as compared to 7 (50 %) of 14 in group B, thus preventive efficacy was clear. 4. There were no severe complications attributable to the radiotherapy, with or without IT-MTX. (author)

  8. Health Risks Awareness of Electronic Waste Workers in the Informal Sector in Nigeria.

    Science.gov (United States)

    Ohajinwa, Chimere M; Van Bodegom, Peter M; Vijver, Martina G; Peijnenburg, Willie J G M

    2017-08-13

    Insight into the health risk awareness levels of e-waste workers is important as it may offer opportunities for better e-waste recycling management strategies to reduce the health effects of informal e-waste recycling. Therefore, this study assessed the knowledge, attitude, and practices associated with occupational health risk awareness of e-waste workers compared with a control group (butchers) in the informal sector in Nigeria. A cross-sectional study was used to assess health risk awareness of 279 e-waste workers (repairers and dismantlers) and 221 butchers from the informal sector in three locations in Nigeria in 2015. A questionnaire was used to obtain information on socio-demographic backgrounds, occupational history, knowledge, attitude, and work practices. The data was analysed using Analysis of Variance. The three job designations had significantly different knowledge, attitude, and practice mean scores ( p = 0.000), with butchers consistently having the highest mean scores. Only 43% of e-waste workers could mention one or more Personal Protective Equipment needed for their job compared with 70% of the butchers. The health risk awareness level of the e-waste workers was significantly lower compared with their counterparts in the same informal sector. A positive correlation existed between the workers' knowledge and their attitude and practice. Therefore, increasing the workers' knowledge may decrease risky practices.

  9. Health Risks Awareness of Electronic Waste Workers in the Informal Sector in Nigeria.

    NARCIS (Netherlands)

    Ohajinwa, Chimere M; Van Bodegom, Peter M; Vijver, Martina G; Peijnenburg, Willie J G M

    2017-01-01

    Insight into the health risk awareness levels of e-waste workers is important as it may offer opportunities for better e-waste recycling management strategies to reduce the health effects of informal e-waste recycling. Therefore, this study assessed the knowledge, attitude, and practices associated

  10. Chronic Lymphocytic Leukemia: Current Concepts.

    Science.gov (United States)

    Yu, Eun-Mi; Kittai, Adam; Tabbara, Imad A

    2015-10-01

    Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, and while in early, asymptomatic stages treatment is not indicated, the threat to the quality of life and increased mortality of patients posed by more advanced-stage disease necessitate therapeutic intervention. Guidelines of when and how to treat are not well-established because CLL is a disease of the elderly and it is important to balance preservation of functional status and control of the disease. Advances in molecular and genetic profiling has led to the ability to identify sub-groups of patients with CLL whose disease may respond to selected therapy. This review discusses current standard therapies in the major sub-groups of CLL based on age and functional status, in both the front-line and relapsed/refractory settings. It also provides a concise review of novel agents that have shown considerable efficacy in CLL. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  11. Hairy cell leukemia: current concepts.

    Science.gov (United States)

    Cannon, Timothy; Mobarek, Dalia; Wegge, Julia; Tabbara, Imad A

    2008-10-01

    Hairy cell Leukemia (HCL) is a chronic lymphoproliferative disorder that was characterized in the late 1950s. HCL is defined, according to the WHO classification, as a mature (peripheral) B-cell neoplasm (1). HCL accounts for between 2-3% of all leukemia cases, with about 600 new cases diagnosed in the U.S. each year (1). HCL occurs more commonly in males, with an overall male to female ratio of approximately 4:1. The median age of onset is 52 years. This disease is seen more commonly in Caucasians and appears to be especially frequent in Ashkenazi Jewish males, with rare occurrence in persons of Asian and African descents (1). Hairy cells are distinct, clonal B cells arrested at a late stage of maturation. They are small B lymphoid cells that possess oval nuclei and abundant cytoplasm with characteristic micro-filamentous ("hairy") projections. They strongly express CD103, CD22, and CD11c (2). These cells typically infiltrate the bone marrow, the spleen, and to a lesser extent the liver, lymph nodes, and skin. Many patients present with splenomegaly and pancytopenia. Other clinical manifestations include recurrent opportunistic infections and vasculitis. Historically, HCL was considered uniformly fatal (2). However, recent treatment advances, using purine analogues such as Cladribine and Pentostatin, led to a significant improvement in prognosis with achievement of high response rates and durable remissions (2).

  12. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

    NARCIS (Netherlands)

    Berndt, Sonja I; Camp, Nicola J; Skibola, Christine F; Vijai, Joseph; Wang, Zhaoming; Gu, Jian; Nieters, Alexandra; Kelly, Rachel S; Smedby, Karin E; Monnereau, Alain; Cozen, Wendy; Cox, Angela; Wang, Sophia S; Lan, Qing; Teras, Lauren R; Machado, Moara; Yeager, Meredith; Brooks-Wilson, Angela R; Hartge, Patricia; Purdue, Mark P; Birmann, Brenda M; Vajdic, Claire M; Cocco, Pierluigi; Zhang, Yawei; Giles, Graham G; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Montalvan, Rebecca; Burdett, Laurie; Hutchinson, Amy; Ye, Yuanqing; Call, Timothy G; Shanafelt, Tait D; Novak, Anne J; Kay, Neil E; Liebow, Mark; Cunningham, Julie M; Allmer, Cristine; Hjalgrim, Henrik; Adami, Hans-Olov; Melbye, Mads; Glimelius, Bengt; Chang, Ellen T; Glenn, Martha; Curtin, Karen; Cannon-Albright, Lisa A; Diver, W Ryan; Link, Brian K; Weiner, George J; Conde, Lucia; Bracci, Paige M; Riby, Jacques; Arnett, Donna K; Zhi, Degui; Leach, Justin M; Holly, Elizabeth A; Jackson, Rebecca D; Tinker, Lesley F; Benavente, Yolanda; Sala, Núria; Casabonne, Delphine; Becker, Nikolaus; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; McKay, James; Staines, Anthony; Chaffee, Kari G; Achenbach, Sara J; Vachon, Celine M; Goldin, Lynn R; Strom, Sara S; Leis, Jose F; Weinberg, J Brice; Caporaso, Neil E; Norman, Aaron D; De Roos, Anneclaire J; Morton, Lindsay M; Severson, Richard K; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Masala, Giovanna; Weiderpass, Elisabete; Chirlaque, María-Dolores; Vermeulen, Roel C H|info:eu-repo/dai/nl/216532620; Travis, Ruth C; Southey, Melissa C; Milne, Roger L; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Clavel, Jacqueline; Zheng, Tongzhang; Holford, Theodore R; Villano, Danylo J; Maria, Ann; Spinelli, John J; Gascoyne, Randy D; Connors, Joseph M; Bertrand, Kimberly A; Giovannucci, Edward; Kraft, Peter; Kricker, Anne; Turner, Jenny; Ennas, Maria Grazia; Ferri, Giovanni M; Miligi, Lucia; Liang, Liming; Ma, Baoshan; Huang, Jinyan; Crouch, Simon; Park, Ju-Hyun; Chatterjee, Nilanjan; North, Kari E; Snowden, John A; Wright, Josh; Fraumeni, Joseph F; Offit, Kenneth; Wu, Xifeng; de Sanjose, Silvia; Cerhan, James R; Chanock, Stephen J; Rothman, Nathaniel; Slager, Susan L

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and

  13. Hyperglycemia during induction therapy is associated with increased infectious complications in childhood acute lymphocytic leukemia

    Science.gov (United States)

    Children with acute lymphocytic leukemia (ALL) are at high risk for developing hyperglycemia. Hyperglycemic adult ALL patients have shorter remissions, more infections, and increased mortality. No corresponding data are available in children. We hypothesized that children with ALL who become hypergl...

  14. Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia | Office of Cancer Genomics

    Science.gov (United States)

    NCI's TARGET Initiative reported the discovery of a novel genetic marker for children with acute lymphoblastic leukemia (ALL) in the January 7, 2009, advance online edition of The New England Journal of Medicine. The genetic alteration identified, IKZF1, should improve clinicians' ability to identify high-risk patients and better assign these patients to appropriate therapy.

  15. Placing of tunneled central venous catheters prior to induction chemotherapy in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Handrup, Mette Møller; Møller, Jens Kjølseth; Frydenberg, Morten

    2010-01-01

    BACKGROUND: Tunneled central venous catheters (CVCs) are inevitable in children with acute lymphoid leukemia (ALL). The aim of this study was to evaluate the risk of CVC-related complications in children with ALL in relation to timing of catheter placement and type of catheter. PROCEDURE: All...

  16. Karyotyping, FISH, and PCR in acute lymphoblastic leukemia: competing or complementary diagnostics?

    NARCIS (Netherlands)

    Olde Nordkamp, Louise; Mellink, Clemens; van der Schoot, Ellen; van den Berg, Henk

    2009-01-01

    BACKGROUND: Chromosomal abnormalities, such as t(9;22)(q34;q11) (ABL/BCR), t(12;21)(p13;q22) (TEL/AML1), and t(11q23) (MLL) are independent