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Risk of secondary leukemia after treatment with etoposide VP‐16) for Langerhans cell histiocytosis in Italian and Austrian‐German populations
Author(s) -
Haupt Riccardo,
Fears Thomas R.,
Heise Ansgar,
Gadner Helmut,
Loiacono Giuseppe,
De Terlizzi Marino,
Tucker Margaret A.
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970328)71:1<9::aid-ijc3>3.0.co;2-y
Subject(s) - etoposide , medicine , cumulative incidence , leukemia , incidence (geometry) , acute promyelocytic leukemia , cohort , langerhans cell histiocytosis , chemotherapy , oncology , pediatrics , disease , biology , retinoic acid , physics , biochemistry , optics , gene
Abstract To estimate the risk of secondary leukemias after treatment with etoposide (VP‐16), we evaluated subjects treated for Langerhans' cell histiocytosis (LCH) according to cooperative protocols in Italy or in Austria, Germany, Holland nd Switzerland (AGDS). For each subjects, information was collected on the cumulative dosages of chemotherapy and radiotherapy received, vital status and occurrence of secondary leukemia. The expected number of leukemias was estimated using age‐specific incidence rates from the cancer registries in Italy and Germany. Standardized incidence ratios (SIR) were used to measure the risk of secondary leukemia among LCH patients. Five leukemias occurred among the 241 Italian study patients (SIR 520), whereas no cases were reported among the 363 AGDS patients. Interestingly, and in contrast to previous descriptions of epipodophyltotoxin‐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 subjects 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 suggests 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 Italian 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 aberrations on chromosomes 15 and 17. Int. J. Cancer, 71:9–13, 1997. © 1997 Wiley‐Liss, Inc.