Document 7MVknN780XYkG8E1Vdv30RRN8

Scb fuema101(1983)30.227-131 /783 Chromosome Pattern and Survival in Acute Non-Lymphocytic Leukaemia in Relation to Age and Occupational Exposure to Potential Mutagenic/Carcinogenic Agents L. BRANDT,F?. MITELMANR:' P. G. N r ~ s s o ~ . ' Deparrmenls of 'Clinical Genetics, 'Internal .Medicine and 30ncologx, University Hospiral. Lund. Sweden The bone marrow karyotype was investigated in 98 patients with acute non-lymphocytic leukaemia (ANLL). The patients were divided into tu'o groups according to age. (1) 47 patients were 2C-54 (median 40)years old. 21 had a histoq of occupational exposure t o chemical solvents, insecticides, or petrol products. and 26 were considered occupationally not having been exposed to such agents. In 4 exposed patients ( I O ' 2 )all bone marrow cells had clonal chromosomal aberrations (designated AA). while also 1 of the non-exposed patients (15 92j were AA. Thus in young ANLL patients. there was no significant association between occupational exposure to potential mutagenicicarcinogenic agents and the AA constitution of the leukaemic cells. (2) 5 1 patients were 55 years of age o r older (median 65 years). 16 were exposed and 8 of a)these (50 had the .4A constitution. 35 patients were non-exposed and only 4 (11%) were AA. It is known from previous studies that the sunival of KYLL patients with A A is extraordinarily short. Accordingly the overrepresentation of A A in exposed patients 55 years or older, was associated with a shorter survival than that of the non-exposed elderly patients. l 3 e results suggest that etiologic factors may influence the clinical course of ANLL. especially in elderly patients. Key wordr: acute leukaemia -cytogenetics -occupational exposure - survi\al Accepted for publication September 7 , 1982 Correspondence to: Dr. L. Brandt, Department of Oncolog). Uni\ersity Hospital, S-22185 Lund. Sueden \dult acute non-lymphocytic leukaemia INLL) is characterized by the incidence chromosome abnormalities in some 507'% the cases (First International Workshop Chromosomes in Leukemia 1978); about of these patients have a mixture of ''rmal and abnormal bone marrow meta'itases (AN) and half have only abnormal metaphases (AX). It is known that survival is especially short in the AA patients (Sakurai & Sandberg 1976, First International Workshop on Chromosomes in Leukemia 1978, Mitelman et al 1978, 1981). Chromosomal abnormality is decidedly more common in patients with a history of occupational exposure to potential mutagenic/ 15' ! I I I I i ! 1 I i I1 i , ! I 1 i i i 228 BRANDT. MITELMAN & NILSSON carcinogenic agents than in those without such exposure (Mitelman et a1 1978, 1979, 1981). Below we present data indicating that the presence or absence of chromosomal abnormality may be related to age: at the time of diagnosis, the proportion of AA patients is especially large in exposed patients who are 55 years or older. MATERIAL AND METHODS This report is based on 98 adult patients with ANLL (47 women and 51 men) aged 20-84 years (median 56 years) in whom the bone marrow kaqotype was established by banding technique. and whose case records contained sufficient information on present or previous occupations to make it possible to classify each of them as either professionally exposed or not exposed to mutagenic!carcinogenic chemical agents. T h e material comprised about 7 5 - 8 0 8 of all ANLL patients in the age group studied who were treated at our hospital during the period 1972-1981. About 2& 25 5% of the total number of patients studied cytogenetically during this period had to be excluded because ambigous or no data were available regarding their previous profession(s) or because chromosome banding examination failed. The case records of all patients were reviewed and the occupation categorized by one of us without any knowledge of the clinical and cytogenetic data. The exposure criteria have been described and discussed previously (Mitelman et a1 1978. 1981). Whenever possible, the information contained in the case records was supplemented by interviews with patients or relatives. or both. Social and private habits were not considered. Patients with leukaemia developing after treatment for another malignant disease. or after a myeloproliferative disorder, were not included. The patients were divided into 2 categories: exposed and non-exposed. Patients occupationally exposed to chemical solvents. insecticides, and petrol products or their combustion residues were referred to the exposed groups. The non-exposed group included mainly house-wives, students and whitecollar workers but also some other occupations were represented where n o history of exposure to chemical agents was apparent. The chromosomes were studied at the time of diagnosis in direct bone marrow preparations or after short term (12-20 h) cultures of bone marrow: the preparh tion and staining methods were described previous, (Mitelman et al 1981). Only clonal chromosomal a h : rations were recorded. An abnormal clone was define; as at least 2 cells with the same extra chromosome c . structural rearrangement, or 3 cells with the sarr,: missing chromosome. The detailed karyotype findinp in 89 of the patients were reported previously (iqire man et a1 1981). In the total material of 98 patients the number ~ , , metaphases analyzed varied between 5-108 (mean XJ, The patients were divided into 2 groups: 20 patient with abnormal metaphases only and 78 patients w , ~ : either only normal metaphases or a mixture of nom, and abnormal metaphases. The mean numbers of me12 phases analyzed in the 2 groups were 29.3 and 29 - respectively. All patients were classified according to the triter,, established by the French-American-British (FAB) c(: operative group [Bennett et al 1976). Survival time u a . calculated from the day of diagnosis. Response to trea: ment was not evaluated since different chemotherap.. schedules were used during the period of study. RESULTS The proportions of patients with abnormai metaphases only (AA) were recorded in : age groups. 1 group comprised 37 patiem 20-54 years old (median 40 years) and the other group 51 patients aged 55 years or older (median 65 years). Among 21 exposed patients in the young age group. TABLE 1 Number of .4A-panenrs (in whom all bone marrow cei! had clonal chromosome aberrarionsl in relarion fo occuparional exposure and age Age 20-54 years 2 55 years Exposed patients Non-exposed patlents Total no. of patients 4/21 (19%) 8/16 ( 5 0 5 ) 4/26 (15 %) 4/35' (11 5 I 47 51 * P < 0.01 ANNL-CHROMOSOblES OCCUPATIONS AND SL!R\.'I\'.AL 229 thelL were 4 (19%) with the A A consti- non-exposed patients was not significantly tution. 4 out of the 26 non-exposed young different, 11and 9 months. respectively. patients ( I 55%) had this chromosomal pat- tern, i.e. the proportion of A A patients was wnilar in young exposed and non-exposed patients. In the old age group. 8 out of 16 exposed patients had the AA-constitution (50 7G) *hereas only 4 out of 35 non-exposed :Iderly patients (11%) were A,4. The dif- ference between exposed and non-exposed tiderl) patients is significant (x' = 9.08. P :0.01). The results are summarized in Table 1. Because there was a predominance Jf men (12 men and 4 women) in the group I f elderly exposed patients compared to the Ion-exposed elderly group (17 men and 18 *omen) it was considered possible that the 4.A constitution might be characteristic for Aderly men with ANLL, thereby explaining DISCCSSIOS Most of the patients in the present study were analyzed with techniques that do not yield an adequate number of metaphases with elongated chromosomes, and therefore subtle rearrangements. such as those recently reported by Yunis et al (1981). would have been o\erlooked. It is therefore possible that the incidence of chromosomal abnormality is underestimated. Nevertheless, the data collected in this investigation support observations made previously by us and others. We have shosn that patients with a history of occupational exposure to potential he difference between exposed and non:\posed patients in the old age group. {owever, among the non-exposed elderly mutagenic/carcinogenic asents have a higher incidence of chromosomal abnormality in their leukaemic cells than those without any l e out of 17 had the AA constitution such history (Mitelman et al 1978, 1979. ! ? Y O ) whereas 7 out of the 12 exposed lderly men (58 %) had this cytogenetic pat- :m (2' = 7.13, P < 0.01). Thus the over- 1981). Thus. clonal chromosomal aberrations were present in 39 of 52 (75%) exposed patients, but in onl! 35 of 110 (32%) -Presentation of the AA constitution non-exposed patients. This observation was mong elderly patients was related to recently confirmed by Golomb et a1 (1982). XPosure but not to sex distribution. These authors anal!zed 74 patients on the AS expected, the different frequency of basis of occupational data classified in the \A-patients was associated with a different same manner as by our group and found 'ognosis in the exposed and non-exposed that 25 of the 58 (43%) non-exposed papatients. 15 exposed (median age 63 tients had a clonal chromosomal abnormai- :ars) and 34 non-exposed patients (median ity, compared with 12 of 16 (75%) exposed 68.5 years) in the old age group have patients, Le. similar figures as found by our :en followed after diagnosis. All exposed group. The present stud! contributes the I h t s died within 9 months with a additional information that the proportion cdian survival time of 2 months. Among of AA-patients is significantly higher among *e34 elderly non-exposed patients, 10 sur- elderly exposed,patients. compared to non- for 9 months or longer with a median exposed patients of this age group. Such ,miVal time of 4.5 months (P = 0.02). The difference was not found among younger survival in the young exposed and ANLL patients. . ANNL-CHROMOSOMES OCCUPATIONS AND SCR\'IV.AL 23 1 p than in the non-exposed patients may therefore support the concept that etiologic factors may influence the clinical course of XNLL. REFERENCES Bennett J M. Catovsky D. Daniel M-T. mandrin G. Galton D A G. Gralnick H R & Sultan C (1976) Proposals for the classification of the acute leukaemias. Br J Haemarol33.451-58. First International Workshop on Chromosomes in Leukemia (1978) Chromosomes in acute non-lymphocytic leukemia. Br J Haemarol39. 311-16. Etzgerald P & McEwan C (1977) Total aneuploidy and agerelated sex chror.;osome aneuploidy in cultured lymphocytes of normal men and women. Hum Genet 39,329-37. Golomb H M, Alimena G. Rowley J D, Vardiman J W, Testa J R & Sovik C (1982) Correlation of Occupation and karyotype in adults with acute nonlymphocytic leukemia. Blood 60,404-11. Hcdner K, Hogstedt B. Kolnig A-M. Mark-Vendel E. 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