Epidemiology of secondary leukemia with reference to chromosomal abnormalities

Secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) have been recognized as one of the most feared long-term complications of cancer therapy. The aim of this case-control study was to determine the prevalence of chromosomal abnormalities and family history of cancer among secondary AML/MDS cases and de novo AML/MDS controls. Study population were 332 MD Anderson Cancer Center patients who were registered between 1986 and 1994. Cases were patients who had a prior invasive cancer before diagnoses of AML/MDS and controls were de novo AML/MDS. Cases (166) and controls (166) were frequency matched on age $\pm$5 years, sex and year of diagnosis of leukemia. Cytogenetic data were obtained from the leukemia clinic database of MD Anderson Cancer Center and data on family history of cancer and other risk factors were abstracted from the patients' medical record. The distribution of AML and MDS among cases was 58% and 42% respectively and among controls 67% and 33% respectively. Prevalence of chromosomal abnormalities were observed more frequently among cases than controls. Reporting of family history of cancer were similar among both groups. Univariate analysis revealed an odds ratio (OR) of 2.8 (95% CI 1.5-5.4) for deletion of chromosome 7, 1.9 (95% CI 0.9-3.8) for deletion of chromosome 5, 2.3 (95% CI 0.8-6.2) for deletion of 5q, 2.0 (95% CI 1.0-4.2) for trisomy 8, 1.3 (95% CI 0.8-2.1) for chromosomal abnormalities other than chromosome 5 or 7 and 1.3 (95% CI 0.8-2.0) for family history of cancer in a first degree relative. The OR remained significant for deletion of chromosome 7 (2.3, 95% CI 1.1-4.8) after adjustment for age, alcohol, smoking, occupation related to chemical exposure and family history of cancer in a first degree relative. Of the 166 secondary AML/MDS patients 70% had a prior solid tumor and 30% experienced hematological cancers. The most frequent cancers were breast (21.1%), non-Hodgkin lymphoma (13.3%), Hodgkin's disease (10.2%), prostate (7.2%), colon (6%), multiple myeloma (3.6%) and testes (3.0%). The majority of these cancer patients were treated with chemotherapy or radiotherapy or both. Abnormalities of chromosome 5 or 7 were found to be more frequent in secondary AML/MDS patients with prior hematological cancer than patients with prior solid tumors. Median time to develop secondary AML/MDS was 5 years. However, secondary AML/MDS among patients who received chemotherapy and had a family history of cancer in a first degree relative occurred earlier (median 2.25 $\pm$ 0.9 years) than among patients without such family history (median 5.50 $\pm$ 0.18 years) (p $<$.03). The implication of exposure to chemotherapy among patients with a family history of cancer needs to be further investigated. ^