Occupational exposure and cytogcnetics in MDWAML Exposure to occupational and environmental factors in MDS. Preliminary results of a case control study.

CNisse, CLorthois, VDorp. E.Eloy, J.M.Haguenoer, P.Fenaux. CHU Lille, France

Apart from cases secondary to antineoplastic agents, ionizing radiation and benzene derivative, etiological factors of MDS are poorly known, and very few case control studies have addressed this subject. We performed a case control study in “de nova” MDS lie without orfor chemo or radiotheraovl. accordino to the method of Siemiatvcki. Contr& (l/patieit) were matched for sex, a&. and areaof residence. The questioiaire (similar to that used by the Cardfff group, Leukemia 1989,3,33) analyzed medical history and environmental and occupational exposure to potentially hazardous toxic compounds by assessing (1) previous jobs (classified by job titles) (2) exposure to a list of 70 chemicals known or suspected to be leukemogenic (3) exposure index (combining the level and duration of exposure) to a given compound. Results of the first 100 pts tested are reported. Median age of the pts was 70 (range 31-87) and there were 28 RA, 10 RARS, 26 RAEB, 12 RAEB-T and 24 CMML, and 54 males and 48 females. No differences in media4 history and hobbies was found in MDS cases and controls, but there were 59 smokers or ex smokers in MDS, and 44 in controls (p<O.O5). For occupational exposure, analysis of job titles found significantly more plant and machine operators and assembfers and significantly less technicians and associate professionals in MDS than in controls (p=O.O12 and p=O.O04, respectively) , ie a higher incidence of jobs with potential exposure to chemicals in MDS cases. Former coal miners were significantly more frequent in MDS cases than in controls (p<O.O5). and there was a trend for more farmers in MDS cases. Analysis of exposure to a list of 70 compounds found significantly more frequent exposure to stone dust. (especially silica, in coal miners) exhaust gases and cereal dust in MDS patients and also a trend for more frequent exposure to binitrotoluene. Finally, in pts and controls previously exposed to a given compound, the exposure index was significantly higher in MDS for petrol and diesel derivatives and for fertilizers. These findings suggest that several compounds may be involved in the pathogen&s of MDS, especially chemicals contained in tobacco smoke, exhaust fumes, petrol and diesel compounds, which probably include benzene and derivatives. Fertilizers and/or cereal dusts could be imolicated in the sliohtlv hiaher number of MDS in farmers. For the exces of MDS in coal r&r& stone dust; a&& exhaust fumes could be implicated. In this study, we could not confirm the higher incidence of MDS in childless persons, and persons exposed to ammonia and to some metals which was found by the Cardiff group.

Epidemiology of MDS in childhood

Henrik Hasle, Gitte Kemdrup, Department of Pediatrics and Pathology, Odense University Hospital, 5000 Odense C, Denmark

Background. Very little is published on the epidemiology of MDS in childhood. Here we present the preliminary results of a population based study. Methods. A data file was constructed from The Danish National Hospital Discharge Registry to include all admissions from 1980 through 1991 of children with a diagnosis of myeloid leukemia or blood cytopenia. All charts were reviewed. Blood and bone marrow smears

from all cases of suspected MDS were reviewed. The cases were categorized according to the FAB classification of MDS, with the exception of CMML in which more than 5 % of myeloblasts in the blood was accepted. Results. A total of 44 cases of MDS were identified (10 RA, 15 RAEB, 5 RAEB-T, I3 CMML) representing 8.6 % of the hematological malignancies in children. The annual incidence was 3.8/million. Boys/girls: 25/l 9. The median age at presentation was 2.2 years (mean 4.9, range 0.2 -14.9). The median age of children with CMML was considerably lower (0.7 years). One child was previously exposed to

chemotherapy, seven had Down syndrome, two had Fanconi anemia. There was no trend in the incidence within the 12-year study period. Conclusion. The incidence of childhood MDS seems to he higher than generally assumed and approximates the incidence of AML in children. Most cases occur in children without any known risk factors. Secondary MDS is relatively uncommon.

K.F. Wong, M.R.C.Path., Y.L. Kwong, M.A.C.Palh , L C Ghan. M.R.C Path.. T.K. Chan, F.R.C.P. Department of Pathology. Dueen Elizabeth Hospital, and Department of Medicme and Pathology, Queen Mary Hospital. Hong Kong

Occupational exposure fo chemicals and solvenfs has been shown lo increase the risk of acufe my&id leukemia (AMi- thaf IS often associated with distinct cytoganetic abnormalities. However. such an association has not been clearly demonstrated I” myelodvsplastic syndrome (MDSI. As part of fm on-going case-conlrol prcmpe~ttve study, we have evaluated the correlation between OccupatIonal exposure fo chemicals and karyotypic abnormalities m MDS and AML. Seventv-six patients diagnosed 8s having MDS and AML sccordlng 10 the FA8 classification &n fw~ regional hospitals in Hong Kong were studied. Those w#th prior chemotherapV or rsdiotherspv were excluded from the studv. Cytogenetic studies were performed of diagnosis. The patients were interviewed by one ol the two invesfioators 1K.F.W.. V.L.K.1 on possible relevant occupsticnal exposures wnhout prior knowledge of the cyfogenetic resulfs using a standard quesuonnase. 56 AML and 20 MDS pafients were Included in the study, comprtsrng 40 females and 36 males with a h.en age of 53 years (range: 17-66 Vesrsl. A hlsfory of occupafional exposure was obtained from 5 pattents an the MDS group and 9 pstlenfs in the AML group ITable 1 I. The agents involved included pesticide. benzene. dyes. glues. lacquers, kerosene and petroleum. On non-parametric analysis, occupallonal exposure and karyotyptc aberrations are nor correlated III AML patienfs (p=O.33). buf are significantly related in MDS p&ems Ip=O.Wl. Moreover. wtfhin the group of pataents with occupatwnal exposure. karyotypic eberratu~ns are more frequently detected In MDS than in AML pafienls lp=O.O2l. These observations WIII be validated by a larger number of patients.

TabI* 1: Correlation of occupdcml .xporur. snd keryotype in MDS end AML

DV3pKlSlS

MDS

AML

Occupational Cvtoaenet~c fmdtnas exposure normal abnormal

+ ,n = 51 0 5 In = 16) a 7

+ I” = 91 6 3 In = 471 23 24