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Background: Trichloroethylene (TCE) has been widely used as an industrial solvent and degreasing agent., Aims: We conducted a meta-analysis of epidemiologic studies of occupational TCE exposure and multiple myeloma (MM) or leukaemia., Methods: We identified a total of eight cohort or case-control studies that enumerated a TCE-exposed study population and presented relative risk (RR) estimates for MM (n = 7) and/or leukaemia (n = 7). The individual studies included aerospace or aircraft workers (n = 3 studies), workers from a transformer manufacturing plant (n = 1 study) and workers from numerous occupations who, based on biomonitoring or extensive industrial hygiene exposure measurements, were likely exposed to TCE (n = 4). We used random effects models to calculate summary relative risk estimates (SRRE). In addition, we examined heterogeneity across studies and the relative influence of each individual study on the overall meta-analysis., Results: No association was observed for MM (SRRE = 1.05, 95% CI: 0.80-1.38; P value for heterogeneity = 0.94) or leukaemia (SRRE = 1.11, 95% CI: 0.93-1.32; P value for heterogeneity = 0.50), based on TCE-exposed subgroup meta-analyses. Study-specific RR estimates for MM ranged between 0.57 and 1.62. RRs for leukaemia ranged between 1.05 and 1.15 in five studies, while one study reported a 2-fold increased RR and another study reported an inverse association of 0.60. All confidence intervals (CIs) for study-specific estimates included 1.0., Conclusions: The results of this meta-analysis do not support an etiologic association between occupational TCE exposure and risk of MM or leukaemia.

In the context of a population-based case-control study in Italy, the authors investigated the possible association between the personal use of hair dyes and non-Hodgkin's lymphoma (NHL), leukemia, multiple myeloma, and Hodgkin's disease. They collected all incident cases of hematolymphopoietic malignancies; the control group was formed with a random sample of the general population. Overall, the authors interviewed 2,737 research subjects and 1,779 control subjects. Among women, the authors found no association between ever using hair dyes and the risk of hematolymphopoietic malignancies. However, for permanent hair dyes, the authors observed a slightly increased risk of lymphocytic leukemia (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 0.8-2.2) and of follicular subtypes of NHL (OR= 1.3; 95% CI = 0.8-2.0). Women who used black hair dye colors were at an increased risk of developing leukemia (OR = 1.9; 95% CI = 1.0-3.4), in particular chronic lymphocytic leukemia (OR = 3.0; 95% CI = 1.1-7.5). In spite of the lack of information on the timing and frequency of hair dye use and the imprecision of the ORs, associations were suggested between leukemia and permanent black hair dye use and follicular NHL and the use of permanent hair dyes.

Background: Choice of follow-up time for an occupational cohort can influence risk estimates. We examined the effects of follow-up time on relative risk estimates for leukemia and multiple myeloma in a cohort of 1,845 rubber hydrochloride workers., Materials and Methods: We generated standardized mortality ratios (SMRs) for yearly follow-ups, beginning each study in 1940 and increasing study end dates from 1950 through 1996. We used Cox proportional hazards modeling to explore the effects of follow-up time on the exposure-response relationship., Results: The SMR for leukemia rose to 13.55 in 1961 and fell nearly monotonically to 2.47 by 1996. Cox modeling suggested interaction between cumulative exposure and time since exposure. A longer time to peak risk was seen for multiple myeloma., Conclusions: Because summary risk estimates change with follow-up time, exposure limits set using these estimates may not adequately protect workers. Consideration of appropriate follow-up time and use of more complex temporal models are critical to the risk assessment process.

Background: Previous studies of a cohort of rubber hydrochloride workers indicated an association between benzene exposure and excess mortality from leukemia and multiple myeloma. To determine whether risks remain elevated with increasing time since plant shutdown, we extended follow-up from 1981 through 1996., Materials and Methods: We evaluated risk using standardized mortality ratios (SMR) and generalized Cox proportional hazards regression models., Results: Five new leukemia cases were observed in benzene-exposed white males, but the summary SMR for this group declined from 3.37 (95% CI = 1.54-6.41) to 2.56 (95% CI = 1.43-4.22). In regression models, cumulative exposure was significantly associated with elevated relative risks for leukemia mortality. Four new multiple myeloma deaths occurred, three of which were in workers judged to be unexposed., Conclusions: These findings reaffirm the leukemogenic effects of benzene exposure and suggest that excess risk diminishes with time.

A multicenter case-control study was conducted in Italy in twelve areas covering a population of 7 million persons with the aim of verifying the hypothesis of an association between exposure to herbicides and to organic solvents and occurrence of lymphoma, leukaemia and multiple myeloma. 3420 cases were recruited in a three-year period (1991-1993), through periodical surveys in the main hospitals in each area. A random sample of the general population (2317 subjects) constitutes the control group. Cases and controls were face to face interviewed by trained personnel. A questionnaire was used asking about personal habits, residential and occupational history, past health status. Preliminary analyses, concerning a total of 1388 cases and 1718 controls, focused risks by occupation. Elevated risks of non Hodgkin's lymphoma (OR: 1.7; IC 95%: 0.92-3.02; based on 28 exposed cases), and of multiple myeloma (OR: 3.6; IC 95%: 1.51-8.63; based on 9 exposed cases) were shown for welders. Among female hairdressers there were elevated risks of non Hodgkin's lymphoma (OR: 1.8; IC 95%: 0.76-4.30; based on 8 exposed cases), multiple myeloma (OR: 3.3; IC 95%: 0.77-14.15; based on 3 exposed cases) and Hodgkin's disease (OR: 2.0; IC 95%: 0.93-4.47; based on 16 exposed cases).

The present case-control study was conducted in an effort to determine if work in the chemical industry is related to excesses of certain hematopoietic and lymphoid neoplasms. Cases who died from non-Hodgkin's lymphoma, multiple myeloma, and leukemia were matched by race, gender, age, year of death, and county of residence to controls who died from cardiovascular disease. A total of 618 (309 matched pairs) white male residents of Kanawha County, WV, aged 23-96, who had died between 1965 and 1990 were identified. Conditional logistic regression was conducted and yielded an association between chemical industry work and death due to non-Hodgkin's lymphoma, multiple myeloma, and lymphoid leukemia among subjects who died at age < 65. These results are consistent with the findings of previous studies linking work in chemical manufacturing to hematopoietic and lymphoid neoplasms, and indicate that the excesses may be related to the occupational exposures in men who died at younger ages.

We utilized data from two Kaiser Permanente medical care programs to evaluate risks of hematopoietic and lymphoproliferative (HLP) malignancies after use of 14 common medications. The subjects were adult cases of non-Hodgkin's lymphoma (NHL) (N = 94), multiple myeloma (N = 159), and leukemia (N = 257) and individually matched controls (N = 695). Abstractors reviewed medical records and recorded medication notations. Using a minimum 5-year exposure lag between first notation and malignancy diagnosis, the risk of NHL was greater among plan members who were prescribed amphetamines [odds ratio (OR) = 2.2; 95% confidence interval (CI) = 1.1-4.8], lidocaine (OR = 2.6; 95% CI = 1.2-5.5), and meprobamate (OR = 2.1; 95% CI = 1.03-4.3). The risk of NHL rose with increasing number of medical record notations for amphetamines; however, there was no association with number of notations for lidocaine or meprobamate. The odds ratio for total leukemia was decreased among patients who took chloramphenicol (OR = 0.4; 95% CI = 0.2-0.97).

The Danish Thorotrast Study was recently reestablished and improved. The cohort has been reidentified and followed up, and now comprises 1003 Thorotrast-exposed patients. For all suspected haematological cases, cytological and histological material has been revised and malignant diseases have been reclassified. The numbers of cases of leukemia and other related haematological disorders were as follows: 16 acute myeloid leukemia (AML); 8 myelodysplastic syndrome (MDS); 1 acute lymphatic leukemia (ALL); 3 chronic myeloid leukemia (CML); 4 non-Hodgkin's lymphoma (NHL); 2 multiple myeloma (MM); 2 myelofibrosis (MF); 2 chronic lymphatic leukemia (CLL). Except for CLL, all cases might be Thorotrast-induced. (Expected number of leukemias: < 2.5.) The findings in the German, Japanese, Portuguese and Danish studies are very similar. Some of the characteristic features include a high incidence of AML with several erythroleukemias, many cases of MDS, and a relatively low incidence of CML. In several studies of leukemia induced by alkylating agents, erythroleukemia is also described as a prominent feature. The possibility exists that a phase of relative predominance of erythroid elements in the bone marrow may be a common and not an unusual feature in the pathogenesis of these secondary leukemias. The findings are also compared with histopathological data from a Danish control group of de novo leukemia patients and from atomic bomb survivors with radiation-induced leukemia. The relative frequency of AML is higher among the Thorotrast-exposed patients than among the Danish control group and the A-bomb survivors. In contrast, low relative frequencies are seen for ALL and CML in Thorotrast cases in comparison with de novo leukemia cases and A-bomb survivors. It can be concluded that differences in relative and absolute frequency of leukemias and myelodysplastic syndrome exist not only between the irradiated populations and the unexposed control group, but even between groups exposed to low-LET (linear energy transfer) and high-LET radiation.

To evaluate the role of agricultural exposures in the development of lymphatic and haemopoietic tumors a population-based case-referent study has been carried out in three health districts of Southern Italy. All incident cases of leukemia, lymphoma and myeloma from 1 July 1987 to 30 June 1989, aged 14 years or more, have been identified (71 subjects). The control group is formed by subjects with other neoplasms. A Job Exposure Matrix, specific to 10 areas, to 6 major crops and to 4 calendar periods, was built for assessing pesticide exposure. To date 100 interviews (to the index subject or to proxies) have been carried out (26 cases and 74 referents). The odds ratio (OR) of hematologic malignancies for agricultural workers was 1.63 [95% Confidence Intervals (95% CI): 0.69-4.34] in the whole sample and 6.00 (95% CI: 1.21-25.52) in the female group. Significative increased risks have been observed for exposure to DDT and creolin (OR = 4.11; 95% CI: 1.16-14.55) and, for leukemia, for cattle breeders (OR = 6.38; 95% CI: 1.46-27.83).

The study is a population-based case-control study on hematolymphopoietic tumors, conducted in west Liguria with high prevalence of exposure to chemicals suspected (about 10%) of increasing the risk of leukaemias or lymphomas and multiple myeloma (pesticides). Cases and control were identified and confirmed during the period 1/1/1990 through 31/12/1993. Cases are identified through periodic contacts with the Pathology, or Hematology or other relevant Department of the Hospitals of west Liguria and Genoa town or University of Genoa where patients living in these area are referred for hematolymphopoietic malignancies. Controls are a random sample of the general population living in each area (using the demographic health archives). The range of the age is 20-74. After identification each case or control is contacted to have his consent to the interview near the home. Informations collected using a most completed questionnaire regard drinking and smoking habit, the addresses and the conditions of the homes where spending the life, particularly hobbies about exposure of pesticides and/or solvents, more important pathological events on the life and the occupational exposure. Actually we are in the phase of identification of cases and controls.

Background: Use of permanent hair dye has been suggested as a risk factor for several types of cancer, although epidemiologic data have not generally supported this hypothesis. Retrospective studies have reported a possible association between hair dyes and hematopoietic cancers., Purpose: Our purpose was to investigate if permanent hair dye was associated with risks of incident lymphoma, leukemia, and multiple myeloma in the Nurses' Health Study, a prospective cohort study of 99,067 women aged 30-55 years in 1976., Methods: Questionnaires regarding medical history and other health-related variables were sent to Nurses' Health Study participants every 2 years from 1976 to 1990. The follow-up for mortality in this cohort exceeds 98%. We identified 244 newly diagnosed cases of hematopoietic cancers, confirmed by pathology reports. Permanent hair dye use was ascertained over four cycles of questionnaires from 1976-1982; status of hair dye use established in 1982 was then used for the remainder of the follow-up time (through 1990). Age-specific incidence rates were calculated and used to compute relative risks (RRs) with 95% confidence intervals (CIs)., Results: We found no evidence of a positive association between ever use of permanent hair dye and all hematopoietic cancers (age-adjusted RR = 0.9; 95% CI = 0.7-1.2) or specific types (Hodgkin's lymphoma [RR = 0.9; 95% CI = 0.4-2.1], non-Hodgkin's lymphoma [RR = 1.1; 95% CI = 0.8-1.6], multiple myeloma [RR = 0.4; 95% CI = 0.2-0.9], chronic lymphocytic leukemia [RR = 0.6; 95% CI = 0.3-1.5], and other leukemias [RR = 0.8; 95% CI = 0.3-1.9]). Further examination of age at first use, duration, frequency, and time since first use and risk of all hematopoietic cancers or non-Hodgkin's lymphoma (the largest diagnostic group), indicated no material associations., Conclusion: In this prospective cohort study, permanent hair dye use is not adversely related to risks of hematopoietic cancers.

Lymphoma, multiple myeloma and leukaemia mortality among French male farmers and farm laborers (1984-1986) has been studied geographically. In each geographical area (89 "départements") exposure to pesticides in arable land has been characterized by an index taking into account different practices in the treatment of various crops as well as an estimate of the time per farmer spent cultivating each crop in 1970. The farmers population as a whole presented an increased mortality for multiple myeloma (SMR = 1.59, 95% CI = 1.32-1.89) and leukaemia (SMR = 1.33, 95% CI = 1.19-1.49) but not for lymphoma (SMR = 1.09, 95%, CI = 0.94-1.26). Using Poisson regression, leukaemia mortality appeared significantly linked to the pesticide exposure index (P = 0.04), after adjustment of farmers' economic status and a linear geographical gradient, whereas no significant relationship was found for lymphoma or multiple myeloma. This result reinforces a similar link reported from a previous French geographical study conducted at a smaller scale within a region.

Mortality was updated another 11 years through 1986 for a previously studied cohort of 2904 male chemical workers who were potentially exposed to styrene and related materials for a year or more between 1937 and 1971. Substantial deficits in mortality from all causes and total cancer were observed in the cohort when it was compared with white males in the United States, and also other chemical workers who were unexposed to styrene-based products. Mortality from leukemia was slightly less than expected during the updated period, in contrast to an excess of lymphatic leukemia observed in the original period. Yet small elevations in risk of other types of lymphatic cancer, particularly multiple myeloma, persisted. The risk of these cancers did not increase with estimated intensity or duration of styrene exposure. The findings are discussed in context with those of studies of similarly exposed workers in related industries.

Exposures to organic solvents (including benzene), ionizing radiation and low frequency electromagnetic fields have been suggested as risk factors for leukemias in adults. Exposure to herbicides of the phenoxyacid variety (2, 4, 5-T; 2, 4-D) has been reported to be associated with an increased risk of non-Hodgkin's lymphomas. In addition several studies have suggested that agricultural workers have an excess risk of hematolymphopoietic malignancies, although no specific agent has yet been identified. Italy is particularly attractive for investigating further these associations, because: a) there is a high prevalence of exposure to solvents in industrial areas (estimated to be 10-16% in the province of Torino, Varese and Florence), and a high prevalence of exposure to herbicides (including phenoxyacides) in agricultural areas; b) there is also considerable extra-occupational exposure to solvents and pesticides; c) competent groups of hematologists exist in several towns, using advanced diagnostic techniques including cytogenetics. We propose therefore to conduct a multicenter population-based case-control study in 11 italian areas, chosen on the basis of a high exposure prevalence. In three years, we intend to interview approximately 1100 cases of leukemia, 1900 cases of lymphoma (Hodgkin and non-Hodgkin) and 400 cases of myeloma; 1900 randomly selected individuals, residents of the same areas, will serve as a population control group. Cases will be all those occurring in the study period among residents of the 11 areas, newly diagnosed. Particular care will be dedicated to diagnostic aspects, including B- and T- cell characterization. Cases and controls will be blindly interviewed by trained personnel.(ABSTRACT TRUNCATED AT 250 WORDS)

There is no doubt about the leukemogenic effect of benzene in man. The evidence is as follows: (1) The incidence of leukemia in shoeworkers exposed to benzene in a period of 8 years in Istanbul was 13.6/100,000, which is significantly higher than that for leukemia in the general population. (2) Following the phase-out of benzene in Istanbul, the number of leukemic workers decreased and none were reported in the subsequent 3 years. (3) The development of leukemia in pancytopenic patients with benzene exposure was observed in 13 out of 51 patients. (4) The differences in the distribution of the types of leukemia in individuals exposed and in nonexposed groups were as follows: acute leukemia 96.1% in the former group, and 46% in the latter group. The high percentages of acute erythroleukemia and preleukemia were other interesting findings in the exposed group. (5) Two cases of leukemia were observed in a 6-year period at a tire cord manufacturing plant with 550 workers. At one location in the plant the concentration of benzene measured by gas chromatography was nearly 110 ppm. Additionally, we have studied 12 cases of malignant lymphoma, four cases of multiple myeloma, and six cases of lung cancer, all of whom were chronically exposed to benzene. The possible role of benzene in the etiology of these malignancies is discussed.

Today there seems to be sufficient data to incriminate benzene as a potent carcinogenic agent causing leukemia, malignant lymphoma, multiple myeloma and lung cancer, as well as numerous disorders of the bone marrow depression. Other factors (such as genetic and individual susceptibility) may have a role in the development of these different types of malignancies and hematologic disorders. In this paper, data concerning all these problems are presented and discussed.