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Annals of Oncology 13:40-43, 2002
© 2002 European Society for Medical Oncology

Genetic susceptibility to Hodgkin's disease and secondary neoplasias: FISH analysis reveals patients at high risk of developing secondary neoplasia

D. M. Lillington1, I. N. M. Micallef1, E. Carpenter1, M. J. Neat1, J. A. L. Amess2, J. Matthews1, N. J. Foot1, T. A. Lister1, B. D. Young1 and A. Z. S. Rohatiner1

1 Cancer Research UK, Department of Medical Oncology 2 Department of Hematology, St Bartholomew's Hospital, London, UK

Abstract

Background: Cytotoxic drugs administered before high-dose therapy (HDT) represent a significant factor in the development of leukemic complications in patients with lymphoid malignancies. This retrospective study was used to detect evidence of abnormal therapy-related myelodysplasia/secondary acute myeloid leukaemia (tMDS/sAML) clones before HDT in a subset of patients who subsequently developed secondary neoplasia.

Patients and methods: 230 patients with non-Hodgkin's lymphoma (NHL) underwent HDT comprising cyclophosphamide and total body irradiation (TBI) with autologous hematopoietic progenitor-cell support. Thirty-three patients have developed tMDS/sAML and 20 of these were screened for the presence of emerging therapy-related abnormalities before HDT. A further 24 patients without evidence of secondary neoplasia were screened using fluorescence in situ hybridisation (FISH).

Results: Significant levels of abnormal cells were identified in 20/20 patients screened who have developed secondary neoplasia compared with only three of 24 patients in the HDT control group who have not. The latter three patients have since died.

Conclusions: The triple FISH assay was developed to detect loss of chromosomal material from 5q31, 7q22 and 13q14. It can potentially identify those patients at risk of alkylating agent-induced leukaemia before they proceed to HDT. Used in a prospective manner, the triple FISH assay could permit more informed clinical management.

cytogenetics; FISH; lymphoma; secondary acute myeloid leukaemia; secondary myelodysplasia; susceptibilty


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