EXPOSURE TO MYELOTOXIC AGENTS AND MYELODYSPLASIA - CASE-CONTROL STUDYAND CORRELATION WITH CLINICOBIOLOGICAL FINDINGS

To better define the role of exposure to myelotoxic agents in the gene sis of myelodysplastic syndrome (MDS), we carried out (a) a case-contr ol study for the determination of the relative risk (RR) of developing MDS, including 178 consecutive patients and 178 sex- and age-matched controls; (b) a study of clinicobiological features in MDS arising aft er occupational exposure to myelotoxic agents and in MDS in 'non-expos ed' patients, The definition of the 'exposure' status was based on a p redetermined questionnaire, with calculation of an 'exposure' index (h ours/ day x days/year x years). Cumulative exposure to pesticides or t o organic solvents, for >2400 h, was recorded in 48 and 25 MDS patient s, respectively, compared to 27 and four controls (P<0.00001; RR 3.74; 95% confidence interval 2.02-5.37). Older age and an excess of refrac tory anaemia with ringed sideroblasts and refractory anaemia with exce ss of blasts was noted among 'exposed' MDS-patients (group 1), compare d to non-exposed MDS-patients (group 2), 68.3% patients in group 1 had clonal chromosome changes, compared with 43.2% patients in group 2. C omplex karyotypes, -7/7q-, -5/5q-, +8, 7p and 17p aberrations were see n more frequently in group 1, whereas a normal karyotype, isolated 5q- or 20q- occurred more frequently in group 2, The association of expos ure to myelotoxic agents with older age at presentation and with unfav ourable chromosome changes accounted for the shorter survival observed in 'exposed' patients. These data show that occupational exposure to pesticides and organic solvents in our region resulted in an increased RR of developing MDS and that a distinct cytogenetic profile was asso ciated with MDS in 'exposed' patients. These findings provide strong i ndirect evidence that these agents may play a role in the pathogenesis of MDS, preferentially targeting some of the chromosome regions which are frequently involved in therapy-related myeloid neoplasias.