RISK OF SECONDARY LEUKEMIA AFTER TREATMENT WITH ETOPOSIDE (VP-16) FORLANGERHANS CELL HISTIOCYTOSIS IN ITALIAN AND AUSTRIAN-GERMAN POPULATIONS

To estimate the risk of secondary leukemias after treatment with etopo side (VP-16), we evaluated subjects treated for Langerhans' cell histi ocytosis (LCH) according to cooperative protocols in Italy or in Austr ia, Germany, Holland and Switzerland (AGDS). For each subject, informa tion was collected on the cumulative dosages of chemotherapy and radio therapy received, vital status and occurrence of secondary leukemia. T he expected number of leukemias was estimated using age-specific incid ence rates from the cancer registries in Italy and Germany. Standardiz ed incidence ratios (SIR) were used to measure the risk of secondary l eukemia among LCH patients. Five leukemias occurred among the 241 Ital ian study patients (SIR 520), whereas no cases were reported among the 363 AGDS patients. Interestingly, and in contrast to previous descrip tions of epipodophyl-lotoxin-related leukemias which are mostly FAB M4 or M5, these leukemias showed typical FAB M3 features, and received a dose of VP-16 >4,000 mg/m(2). Among the AGDS cohort, very few subject s were exposed to high doses of VP-16. The risk of secondary acute non -lymphoblastic leukemia (s-ANLL) among the Italian subjects exposed to VP-16 was more than 1,000 times greater than expected. The study sugg ests that high doses of VP-16 appear to increase the risk of s-ANLL in LCH patients. The fact that all the leukemias described in the Italia n LCH cohort were promyelocytic, and evidence of a higher incidence of promyelocytic leukemias among Italians and Latinos, suggest that high doses of etoposide in subjects of Latino origin may lead to aberratio ns on chromosomes 15 and 17. (C) 1997 Wiley-Liss, Inc.