Neural Correlates of Risk Perception: HIV vs. Leukemia

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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.

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

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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.

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

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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...

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

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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

Occupation and leukemia in Nordic countries

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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....

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

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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.

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

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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.

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.

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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.

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

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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.

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

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

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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.

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

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

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.

Risk Groups for Childhood Acute Lymphoblastic Leukemia

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... 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 ...

[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

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...

Childhood Leukemia and Primary Prevention

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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

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.)

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.)

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)

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

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)

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.

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...

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.

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

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.)

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.

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 ...

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...

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 ...

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.

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.

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.

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

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

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...

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

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...

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

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

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...

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 ...

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)

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)

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.

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.

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

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...

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.

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.

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 ...

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

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

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

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

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)

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.

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.

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.

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 ...

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.

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.

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.

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

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

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

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.

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.

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.

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).

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)

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)

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.

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.

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...

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

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.

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

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

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

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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

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.

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

Parental and infant characteristics and childhood leukemia in Minnesota

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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.

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.

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...

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

Leukemia -- Chronic T-Cell Lymphocytic

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... 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 ...

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.

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...

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.)

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.

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

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

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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.

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...

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.

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

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.)

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

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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

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

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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

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)

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.

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

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

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

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.

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.

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.

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.

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...

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...

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)

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 ...

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 ...

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

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

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...

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.

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...

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…

[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.

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

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

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.

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.

Leukemia-Initiating Cells in T-Cell Acute Lymphoblastic Leukemia

OpenAIRE

Tan, Shi Hao; Bertulfo, Fatima Carla; Sanda, Takaomi

2017-01-01

T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC) theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs), which can generate leukemia in a xenograft setting, have been found in both human T-AL...

Atomic bomb irradiation-induced leukemias revisited. Summary data of 50 years-long term follow up study on survivors

International Nuclear Information System (INIS)

Tomonaga, Masao; Matsuo, Tatsuki; Preston, D.L.; Bennett, J.M.

1997-01-01

The Life Span Study (LSS) on 93,741 survivors (fixed cohort) and the Open City Study (OCS) on all survivors (unfixed) irrespective of whether they belonged to LSS or not, have been conducted in parallel over 45 years to ensure reliable case detection. We adopted the FAB classification for acute leukemias and for exposure dose of individual survivors, the new dosimetry system 1986 (DS86). In LSS, 221 leukemia cases were analysed. There was strong evidence of radiation-induced risks for acute myeloid leukemia (AML), acute lymphoid leukemia (ALL) and chronic myeloid leukemia (CML), but not for adult T-cell leukemia and chronic lymphocytic leukemia. There was also significant difference between three major types with respect to the effects of age at bombing and sex, and in the temporal pattern of the elevated risks. For AML the dose response function was non-linear, whereas there was no evidence against linearity for ALL and CML. The hypothesis of a 0.5 Gy threshold could be rejected for three major types of leukemia. Excess Absolute Risk (EAR) estimates in cases per 10,000 Person Year Sievert (PYSv) were 0.6, 1.1, 0.9 for ALL, AML and CML, respectively. The corresponding relative risk at 1.0 Sv were 9.1, 3.3, 6.2, respectively. Although childhood exposure <15 age at bombing apparently induced three major types, the age-related highest risk was observed for ALL. In OCS, 413 cases with DS86 estimates were used for analysis. Type specific incidence rates were calculated indirectly by using the over all incidence of leukemia from LSS data and multiplying these values by the corresponding proportions of cases in OCS. In conjunction with LSS data, the effects of radiation were significantly greater on the incidences of ALL and CML than on that of AML. In the high dose group there was a strong evidence for shorter incubation time and faster decline of elevated risk for ALL and CML than for AML. AML risk was apparently persistent through 1980. (K.H.)

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

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.

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)

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...

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. ...

[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

INCIDENCE OF ACUTE MYELOID LEUKEMIA AFTER BREAST CANCER

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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

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)

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.

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.

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 ...

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 ...

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.

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.

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.

Kelainan Hemostasis pada Leukemia

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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

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.

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.

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 ...

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.

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.)

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%.

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

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

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

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

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...

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)

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

Leukemia incidence in the atomic bomb survivor Life Span Study, 1950 - 87

International Nuclear Information System (INIS)

Preston, D.L.; Mabuchi, K.; Kusumi, S.; Izumi, S.

1992-01-01

The Radiation Effects Research Foundation (RERF) is currently preparing a series of reports on cancer incidence in the Life Span Study (LSS) cohort of atomic bomb survivors for the period from 1950 to 1987. One of these reports will present analyses of the data on the risk of hematopoietic cancers including leukemia, malignant lymphoma, and multiple myeloma. These analyses add an additional 11 years of follow-up to the previous comprehensive analysis of the LSS leukemia data. In this presentation, these data are presented and the methods being used modeling the leukemia risks are outlined. An analysis of the leukemia data pooled over subtypes will be used to illustrate these methods. It is shown that the data suggest a non-linear, concave upward dose response and that the temporal pattern of the radiation-induced excess absolute risks (EARs) depends on age-at-exposure and sex. There is no evidence of city differences in the EAR in this pooled analysis. The results suggest that the EARs for the youngest survivors were initially much higher and have declined more rapidly than those for older survivors. The same general pattern is seen both sexes, but the initial peak incidence is somewhat lower and the rate of decline less rapid for women than for men. (author)

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)

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.

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

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.

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.)

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

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).

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

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)

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.

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.

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...

Population-based case-control study of childhood leukemia in Shanghai

International Nuclear Information System (INIS)

Shu, X.O.; Gao, Y.T.; Brinton, L.A.; Linet, M.S.; Tu, J.T.; Zheng, W.; Fraumeni, J.F. Jr.

1988-01-01

A population-based case-control interview study of 309 childhood leukemia cases and 618 healthy population control children was conducted in urban Shanghai, China. Like some studies in other countries, excess risks for both acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL) were associated with intrauterine and paternal preconception diagnostic x-ray exposure, and with maternal employment in the chemical and agricultural industries during pregnancy. ANLL was linked to maternal occupational exposure to benzene during pregnancy, whereas both ALL and ANLL were significantly associated with maternal exposure to gasoline and the patient's prior use of chloramphenicol. New findings, previously unsuspected, included an association of ANLL with younger maternal age at menarche (odds ratio [OR] = 4.3; 95% confidence interval (CI) = 1.3-13.9); a protective effect for long-term (greater than 1 year) use of cod liver oil containing vitamins A and D for both ALL (OR = 0.4; 95% CI = 0.2-0.9) and ANLL (OR = 0.3; 95% CI = 0.1-1.0); and excess risks of ANLL among children whose mothers were employed in metal refining and processing (OR = 4.6; 95% CI = 1.3-17.2) and of ALL associated with maternal occupational exposure to pesticides (OR = 3.5; 95% CI = 1.1-11.2). No relationships were found with late maternal age, certain congenital disorders, or familial occurrence, which have been related to childhood leukemia in other studies. In contrast with other reports, an excess of leukemia, primarily ANLL, occurred among second or later-born rather than firstborn children

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

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...

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

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.

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

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%.

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....

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)

Acute Lymphoblastic Leukemia in a Man Treated With Fingolimod for Relapsing Multiple Sclerosis

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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.

Atomic bomb and leukemia

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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).

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)

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

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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.

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

Mosaic Down syndrome and acute lymphoblastic B cell-leukemia. Case report

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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.

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

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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.

Leukemia-Initiating Cells in T-Cell Acute Lymphoblastic Leukemia.

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Tan, Shi Hao; Bertulfo, Fatima Carla; Sanda, Takaomi

2017-01-01

T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC) theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs), which can generate leukemia in a xenograft setting, have been found in both human T-ALL patients and animal models, the nature and origin of LICs are largely unknown. In this review, we discuss recent studies on LICs in T-ALL and the potential mechanisms of LIC emergence in this disease. We focus on the oncogenic transcription factors TAL1, LMO2 , and NOTCH1 and highlight the significance of the transcriptional regulatory programs in normal hematopoietic stem cells and T-ALL.

Leukemia-Initiating Cells in T-Cell Acute Lymphoblastic Leukemia

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Shi Hao Tan

2017-09-01

Full Text Available T-cell acute lymphoblastic leukemia (T-ALL is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs, which can generate leukemia in a xenograft setting, have been found in both human T-ALL patients and animal models, the nature and origin of LICs are largely unknown. In this review, we discuss recent studies on LICs in T-ALL and the potential mechanisms of LIC emergence in this disease. We focus on the oncogenic transcription factors TAL1, LMO2, and NOTCH1 and highlight the significance of the transcriptional regulatory programs in normal hematopoietic stem cells and T-ALL.

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

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

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.

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

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.

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.

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.

Occurrence of chronic lymphocytic leukemia in patients with chronic myelogenous leukemia

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Pritish K Bhattacharyya

2013-01-01

Full Text Available Chronic lymphocytic leukemia (CLL is the most common leukemia of adults in the western world and constitutes about 33% of all leukemia′s. The incidence of CLL increases with age and are more common in older population. Chronic myeloid leukemia (CML on the contrary occurs in both young adults and elderly and is a chronic myeloproliferative disease that originates from abnormal pluripotent stem cells and results in involvement of multiple hematopoietic lineages, but predominantly myeloid and less commonly lymphoid. Association between CLL and myeloid malignancies (CML, acute myeloid leukemia and MDS, myelodysplastic syndrome is rare. In literature documenting CLL and CML in same patients, occur either simultaneously or CML is preceded by CLL.

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)

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)

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

DEFF Research Database (Denmark)

Schmiegelow, Kjeld; Müller, Klaus Gottlob; Mogensen, Signe Sloth

2017-01-01

During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal...... useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall...... obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically...

Donor T cells primed on leukemia lysate-pulsed recipient APCs mediate strong graft-versus-leukemia effects across MHC barriers in full chimeras.

Science.gov (United States)

Ghosh, Arnab; Koestner, Wolfgang; Hapke, Martin; Schlaphoff, Verena; Länger, Florian; Baumann, Rolf; Koenecke, Christian; Cornberg, Markus; Welte, Karl; Blazar, Bruce R; Sauer, Martin G

2009-04-30

Antigen-presenting cells (APCs) of host origin drive graft-versus-leukemia (GVL) effects but can also trigger life-threatening graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) across major histocompatibility complex (MHC) barriers. We show that in vitro priming of donor lymphocytes can circumvent the need of recipient-derived APCs in vivo for mediating robust GVL effects and significantly diminishes the risk of severe GVHD. In vitro, generated and expanded T cells (ETCs) mediate anti-leukemia effects only when primed on recipient-derived APCs. Loading of APCs in vitro with leukemia cell lysate, chimerism status of the recipient, and timing of adoptive transfer after HCT are important factors determining the outcome. Delayed transfer of ETCs resulted in strong GVL effects in leukemia-bearing full chimera (FC) and mixed chimera (MC) recipients, which were comparable with the GVL/GVHD rates observed after the transfer of naive donor lymphocyte infusion (DLI). Upon early transfer, GVL effects were more pronounced with ETCs but at the expense of significant GVHD. The degree of GVHD was most severe in MCs after transfer of ETCs that had been in vitro primed either on nonpulsed recipient-derived APCs or with donor-derived APCs.

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

Addition of Arsenic Trioxide into Induction Regimens Could Not Accelerate Recovery of Abnormality of Coagulation and Fibrinolysis in Patients with Acute Promyelocytic Leukemia.

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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

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

Experimental studies of leukemia

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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.)

Extramedullary leukemia in children with acute myeloid leukemia

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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....

Leukemia-associated antigens in man.

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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.

Secondary leukemia associated with a conventional dose of etoposide: review of serial germ cell tumor protocols.

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Nichols, C R; Breeden, E S; Loehrer, P J; Williams, S D; Einhorn, L H

1993-01-06

Case reports have suggested that treatment with high-dose etoposide can result in development of a unique secondary leukemia. This study was designed to estimate the risk of developing leukemia for patients receiving conventional doses of etoposide along with cisplatin and bleomycin. We reviewed the records at Indiana University of all untreated patients entering clinical trials using etoposide at conventional doses (cumulative dose, 2000 mg/m2 or less) for germ cell cancer between 1982 and 1991. The records of all patients who received a chemotherapy regimen containing etoposide, ifosfamide, or cisplatin after failing to respond to primary chemotherapy were also reviewed. Between 1982 and 1991, 538 patients entered serial clinical trials with planned cumulative etoposide doses of 1500-2000 mg/m2 in combination with cisplatin plus either ifosfamide or bleomycin. Of these 538 patients, 348 received an etoposide combination as initial chemotherapy and 190 received etoposide as part of salvage treatment. To date, 315 patients are alive, with median follow-up of 4.9 years, and 337 patients have had follow-up beyond 2 years. Two patients (0.37%) developed leukemia. One developed acute undifferentiated leukemia with a t(4;11) (q21;q23) cytogenetic abnormality 2.0 years after starting etoposide-based therapy, and one developed acute myelomonoblastic leukemia with no chromosome abnormalities 2.3 years after beginning chemotherapy. During this period, several hundred patients were treated with etoposide-based chemotherapy and did not enter clinical trials. Three of these patients are known to have developed hematologic abnormalities, including one patient with acute monoblastic leukemia with a t(11;19)(q13;p13) abnormality. Secondary leukemia after treatment with a conventional dose of etoposide does occur, but the low incidence does not alter the risk-to-benefit ratio of etoposide-based chemotherapy in germ cell cancer. The reports of leukemia associated with high doses of

Vorinostat in Treating Patients With Acute Myeloid Leukemia

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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

Driving Toward Precision Medicine for Acute Leukemias: Are We There Yet?

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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

Leukemia in humans following exposure to ionizing radiation. A summary of the findings in Hiroshima and Nagasaki and comparison with other human experience

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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.

Total body irradiation in the bone marrow transplantation in leukemia:an experience

International Nuclear Information System (INIS)

Zapatero, A.; Martin de Vidales, C.; Pinar, B.; Marin, A.; Cerezo, L.; Dominguez, P.; Perez, A.

1996-01-01

The purpose of this report was to evaluate long-term survival and morbidity of fractioned total body irradiation (TBI) prior to allogeneicbone marrow transplantation (BMT) for leukemia. From June 1985 to May 1992, 94 patients with acute leukemia and chronic myelogenous leukemia (CML), were treated with high dose cyclophosphamide(CY) and fractionated TBI to a total dose of 12 Gy in six fractions prior to allogeneic BMT. The Kaplan-Meier 5-year overall survival and disease-free survival were 53% +-6 and 48%+- respectively for patients with standard risk disease (first remission of acute leukemia and first chronic phase of CML), and 24%+-7 and 21%+-6 for patients with more advanced disease (p=3D0.01). The incidence of interstitial pneumonitis (IP), venoocclusive disease of the liver (VOD) and grade=3D>II acute graft-versus-host disease (GVHD) were respectively 15%, 29% and 51%. Fractionated TBI combined with high dose CY before allogeneic BMT for leukemia is an effective treatment in prolonging relapse-free survival witha low incidence of lung toxicity. (Author) 13 refs

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

Pregnancy, maternal tobacco smoking and early age leukemia in Brazil

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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.

Acute Lymphocytic Leukemia

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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 ...

Acute Myeloid Leukemia

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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 ...

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. ...

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. ...

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.)

Acute lymphoblastic leukemia in children with Down syndrome

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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...

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.

The Role of Hematopoietic Stem-Cell Transplantation in First Remission in Pediatric Acute Lymphoblastic Leukemia: A Narrative Review

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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.

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

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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....

Radiotherapy for leukemia in children, (1). Radiotherapy for central nervous system leukemia

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Miyazaki, Toru; Konishi, Kiyosaburo; Sato, Noriko; Fujiwara, Fumihiro [Maizuru National Hospital, Kyoto (Japan)

1983-07-01

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.

Is high dose methotrexate without irradiation of the brain sufficiently effective in prevention of CNS disease in children with acute lymphoblastic leukemia?

International Nuclear Information System (INIS)

Cap, J.; Foltinova, A.; Kaiserova, E.; Mojzesova, A.; Sejnova, D.; Jamarik, M.

1998-01-01

We present 5-year results of treatment in 93 children suffering from acute lymphoblastic leukemia using two therapeutic protocols containing multidrug chemotherapy including high dose methotrexate. We could ascertain different results in standard and high risk patients. In a group of 62 children with standard risk we observed improvement in complete remission rate being 98.9% after induction phase of therapy, only one patient died on septicemia. Relapse rate in this group was 21.2% and that 14. 7% in the bone marrow and 6.5% in CNS and no testicular relapse at all. In the group of 31 children with high risk leukemia all patients achieved complete remission. Only one of them died on acute pancreatitis due to toxicity. Overall relapse rate in this group was 28.9% with 12.8% of medullary relapse and 16.1 % of CNS relapse. The last one was significantly higher than in the previous study when brain irradiation was a part of therapeutic procedure. It seems that this treatment is effective mainly in the standard risk leukemia, however, in the high risk leukemias this procedure appears to be less effective in preventing CNS leukemia. In this group of patients irradiation of the brain need to be enclosed in the therapy. (authors)

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

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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.

HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse.

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Martelli, Massimo F; Di Ianni, Mauro; Ruggeri, Loredana; Falzetti, Franca; Carotti, Alessandra; Terenzi, Adelmo; Pierini, Antonio; Massei, Maria Speranza; Amico, Lucia; Urbani, Elena; Del Papa, Beatrice; Zei, Tiziana; Iacucci Ostini, Roberta; Cecchini, Debora; Tognellini, Rita; Reisner, Yair; Aversa, Franco; Falini, Brunangelo; Velardi, Andrea

2014-07-24

Posttransplant relapse is still the major cause of treatment failure in high-risk acute leukemia. Attempts to manipulate alloreactive T cells to spare normal cells while killing leukemic cells have been unsuccessful. In HLA-haploidentical transplantation, we reported that donor-derived T regulatory cells (Tregs), coinfused with conventional T cells (Tcons), protected recipients against graft-versus-host disease (GVHD). The present phase 2 study investigated whether Treg-Tcon adoptive immunotherapy prevents posttransplant leukemia relapse. Forty-three adults with high-risk acute leukemia (acute myeloid leukemia 33; acute lymphoblastic leukemia 10) were conditioned with a total body irradiation-based regimen. Grafts included CD34(+) cells (mean 9.7 × 10(6)/kg), Tregs (mean 2.5 × 10(6)/kg), and Tcons (mean 1.1 × 10(6)/kg). No posttransplant immunosuppression was given. Ninety-five percent of patients achieved full-donor type engraftment and 15% developed ≥grade 2 acute GVHD. The probability of disease-free survival was 0.56 at a median follow-up of 46 months. The very low cumulative incidence of relapse (0.05) was significantly better than in historical controls. These results demonstrate the immunosuppressive potential of Tregs can be used to suppress GVHD without loss of the benefits of graft-versus-leukemia (GVL) activity. Humanized murine models provided insights into the mechanisms underlying separation of GVL from GVHD, suggesting the GVL effect is due to largely unopposed Tcon alloantigen recognition in bone marrow. © 2014 by The American Society of Hematology.

Occupational exposure to solvents and acute myeloid leukemia

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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...

Secondary Leukemia Associated with the Anti-Cancer Agent, Etoposide, a Topoisomerase II Inhibitor

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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<...