Leucemias y radiación: juicio causal según los criterios de Sir Austin Bradford Hill / Causal judgment by Sir Austin Bradford Hill criteria: leukemias and radiation

El cometido del presente trabajo es la lectura interpretativa con base en la propuesta de inferencia causal de Austin Bradford Hill, del documento Radiation-related leukemia in Hiroshima and Nagasaki, 1946-1964. I. Distribution, incidence and appearance time. El documento informado por el comité de las víctimas de la bomba atómica cumple con la totalidad de los nueve “criterios” propuesto por Hill, y entre las limitaciones se cuentan la presunciones de homogeneidad genética de los sujetos expuestos y linealidad de los efectos de las radiaciones en la leucemia, además del hecho de sólo considerar la edad como variable confusora. Por otra parte, el número de muertes por leucemia, patrón de oro de la sensibilidad y la especificidad del sistema de vigilancia del estudio de duración de la vida, fue 61 muertes por leucemia entre los supervivientes situados dentro de 1500 metros del epicentro de la explosión y 25 muertes en el grupo que recibió radiación estando entre 1501 y 10000 metros, lo que habla de posible subregistro de casos y de sobrediagnóstico por la sumatoria de criterios empleados. Los “criterios” de Hill no son reglas lógicas sino metodológicas, que ayudan en el proceso de decisión sobre la inferencia causal en epidemiología. Se apartan de la discusión de si las inferencias a partir de ellos se ajustan a la lógica inductiva o a la deductiva, y deben entenderse pragmáticamente como “inferencias de la mejor explicación” en el contexto de la abducción. La única conclusión permitida dentro del marco de la “inferencia de la mejor explicación”, es que se tienen buenas razones para considerar seriamente la hipótesis que la asociación estadística que se estudia, es una relación causal.

Occupational Lymphohematopoietic Cancer in Korea

The purpose of this study was to review the existing studies on lymphohematopoietic (LHP) cancer in Korea, estimate the prevalence of workers exposed to carcinogens, and determine the population attributable fraction (PAF) of leukemia. Two case series and 4 case reports were reviewed. Using official statistics, the prevalence of benzene exposure and ionizing radiation exposure was estimated. Based on the prevalence of exposure and the relative risk, The PAF of leukemia was calculated. Between 1996 and 2005, 51 cases of LHP cancer were reported from the compensation system. Greater than 50% of occupational LHP cancer was leukemia, and the most important cause was benzene. In a cohort study, the standardized incidence ratio was 2.71 (95% CI, 0.56-7.91). The prevalence of exposure was 2.5% and 2.2% in 1995 and 2000, respectively. Using the 1995 prevalence, 3.6-4.8% and 0.1% of cases with leukemia were attributable to benzene and ionizing radiation exposure, respectively, which resulted in 39.7-51.4 cases per year. Benzene is the most important cause of occupational leukemia in Korea. Considering the estimated PAF in this study, the annual number of occupational LHP cancer (51 cases during 10-yr period), might be underreported within the compensation system.

Magnetic fields and acute lymphoblastic leukemia in children: a systematic review of case-control studies / Campos magnéticos e leucemia linfocítica aguda em crianças: revisão sistemática de estudos caso-controle

Leukemia incidence in children has increased worldwide in recent decades, particularly due to the rise in acute lymphoblastic leukemia. Studies have associated exposure to non-ionizing radiation generated by low frequency magnetic fields with childhood leukemia. The current article reviews the case-control studies published on this subject. Of 152 articles tracked in different databases, ten studies from North America, Asia, and Europe met the defined selection criteria, with patients diagnosed from 1960 to 2004. Methodological limitations were observed in these articles, including difficulties with the procedures for assessing exposure. An association may exist between exposure to low frequency magnetic fields and acute lymphoblastic leukemia in children, but this association is weak, preventing the observation of consistency in the findings. Future studies from a wider range of geographic regions should focus on the analysis of acute lymphoblastic leukemia, which is the subtype with the greatest impact on the increasing overall incidence of childhood leukemia.

A incidência de leucemias em crianças tem aumentado nas últimas décadas no mundo, com influência predominante da leucemia linfocítica aguda, principal subtipo em crianças. Estudos têm relacionado a exposição às radiações não-ionizantes geradas pelos campos magnéticos de baixa freqüência com leucemia infantil. Neste artigo foram revisados os estudos caso-controle publicados sobre essa questão. Dos 152 artigos localizados em diferentes bases de dados, dez estudos da América do Norte, Ásia e Europa preencheram os critérios de seleção, comportando pacientes diagnosticados entre 1960 e 2004. Algumas limitações metodológicas foram observadas como dificuldades nos procedimentos de avaliação da exposição. É possível a existência de associação entre exposição a campos magnéticos de baixa freqüência e leucemia linfocítica aguda em crianças, porém, a força desta associação é tênue, impedindo observar consistência entre os resultados. Futuros estudos, com maior diversidade de regiões, deveriam concentrar-se na análise da leucemia linfocítica aguda, pois é o subtipo com maior influência na incidência crescente da leucemia infantil.

Four Cases of Hematologic Malignancy Following Radioactive Iodine Therapy for Thyroid Cancer / 대한진단검사의학회지

Ionizing radiation including I131 might produce chromosomal translocation, causing hematologic malignancy. The incidence of leukemia following radioactive iodine treatment for thyroid cancer has been reported to be approximately 0.1 to 2.0% in Western countries, whereas fewer cases have been reported in Korea. We hereby report four cases of secondary hematologic malignancy, who received iodine therapy for thyroid cancer after thyroidectomy: two cases of acute lymphoblastic leukemia with t(9;22)(q34;q11.2), a case of MDS with 5q deletion, and a case of MDS with normal karyotype. Three cases of hematologic malignancy have developed after cumulative dosage of less than 800 mCi. The treatment intervals in two cases were less than 12 months, and the other two cases had I131 therapy only once. Assessment of causality using the Naranjo probability scale for adverse drug reactions showed that a 'possible' relationship existed between the use of I131 and secondary hematologic malignancy in all of the four cases in this report.

Acute childhood leukemias and exposure to magnetic fields generated by high voltage overhead power lines - a risk factor in Iran.

Many investigators have studied the effects of Extremely Low Frequency-Magnetic Fields generated by ordinary and domestic power lines, as a risk factor in acute leukaemias of children, but there are limited information available regarding very high voltage overhead power lines. Children in developing countries sometimes live very close to such structures and we have registered several patients with acute leukaemias appearing in clusters. In the present study we have analyzed 60 consecutively diagnosed patients with acute leukaemias, and 59 matched controls in a provincial capital city in North-Western Iran. After provision of consent, a detailed form was filled in, and a visit to the present (or previous) residential areas of both groups was arranged. The locations of the very high voltage power lines (123, 230, 400 kilo volts), were noted in each area, if present, and their distances from the houses under study were detected. The expected intensities of the Magnetic Fields (B) were calculated having the mean intensity of the electrical current and other line characteristics, by means of relevant equations. Fourteen patients in the case group (23.5%) were living near the high voltage power lines in distances < or = 500 meters. (Mean B = 0.6 microTeslas, microT). In the control group at the same distance, the figure was 2 children (3.3%) (Mean B = 0.35 microT). Statistically, the likelihood of leukaemia was increased considerably in this distance (Odds ratio (OR) = 8.67, 95% Confidence Interval (CI) = 1.74- 58.4, P value= 0.001). On the other hand 15 pts (25 %) in the leukaemia group were experiencing Magnetic fields above 0.45 microT in comparison to 5 in the control group ( 8.5% )(OR = 3.60, 95% CI = 1.11-12.39, P = 0.01). More children in developing countries like Iran live close to very high voltage lines, and they experience relatively more harmful effects from the Magnetic Fields, in comparison with children in developed countries. Residence near very high voltage overhead power lines, in distances < or = 500 meters, and Magnetic Fields >0.45 microT, should be considered a risk factor for the pathogenesis of acute leukaemias in children.

Gamma radiation induced leukemia in ICRC strain of mice: a murine model closely simulating human disease for experimental chemotherapy.

We report here a murine model of transplantable lymphoblastic leukemia closely simulating human disease in albino mice of ICRC strain. Both male and female mice of this strain developed leukemia with high incidence (approximately 70%) following whole body exposure to 60Co Gamma Rays (Dose: 1.5 Gray/Week x4). The latent period for development of leukemia was six months. In the leukemic mice there is marked leucocytosis with presence of lymphoblasts in peripheral blood. These blasts infiltrate various organs like liver, spleen, kidney, lymph nodes, testes and brain, Neoplastic cells are T lymphoblasts expressing weak Thy 1.2 membrane antigen and found sensitive to anticancer drugs. Salient features of the murine model are described.

Therapy related acute non-lymphocytic leukemia: report of 4 cases.

Four cases of acute myelodysplastic-non-lymphocytic leukemia secondary to cytotoxic agents were reported. Primary diseases were breast cancer (1 patient), ovarian cancer (2 patients) and multiple myeloma (1 patient). All except one (with multiple myeloma) were in clinical remission of their primary diseases. Common cytotoxic agent used was melphalan. Median total drug dose and median latent period from diagnosis of primary diseases were 1299 mg and 63 months respectively. None with the exception of one received specific treatment. All died except one who is in a very poor condition. Survival from the diagnosis of hematologic diseases ranged from 3-9 months. Clinical features, cytogenetic findings, pathogenetic mechanism and risk of the disease were briefly discussed.