Risk of secondary leukemia after treatment with etoposide (VP-16) for Langerhans' cell histiocytosis in Italian and Australian-German populations

Riccardo Haupt, Thomas R. Fears, Ansgar Heise, Helmut Gadner, Giuseppe Loiacono, Marino De Terlizzi, Margaret A. Tucker

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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 and Switzerland (AGDS). For each subject, 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 epipodophylotoxin-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/m2. 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.

Original languageEnglish
Pages (from-to)9-13
Number of pages5
JournalInternational Journal of Cancer
Volume71
Issue number1
DOIs
Publication statusPublished - 1997

Fingerprint

Langerhans Cell Histiocytosis
Etoposide
Leukemia
Population
Germany
Austria
Switzerland
Netherlands
Therapeutics
Incidence
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hispanic Americans
Italy
Radiotherapy Dosage
Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 17
Registries
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Risk of secondary leukemia after treatment with etoposide (VP-16) for Langerhans' cell histiocytosis in Italian and Australian-German populations. / Haupt, Riccardo; Fears, Thomas R.; Heise, Ansgar; Gadner, Helmut; Loiacono, Giuseppe; De Terlizzi, Marino; Tucker, Margaret A.

In: International Journal of Cancer, Vol. 71, No. 1, 1997, p. 9-13.

Research output: Contribution to journalArticle

Haupt, Riccardo ; Fears, Thomas R. ; Heise, Ansgar ; Gadner, Helmut ; Loiacono, Giuseppe ; De Terlizzi, Marino ; Tucker, Margaret A. / Risk of secondary leukemia after treatment with etoposide (VP-16) for Langerhans' cell histiocytosis in Italian and Australian-German populations. In: International Journal of Cancer. 1997 ; Vol. 71, No. 1. pp. 9-13.
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