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


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.
Lillington
D M
DM
Cancer Research UK, Department of Medical Oncology, St Bartholomew's Hospital, London. D.Lillington@cancer.org.uk
Micallef
I N M
IN
Carpenter
E
E
Neat
M J
MJ
Amess
J A L
JA
Matthews
J
J
Foot
N J
NJ
Lister
T A
TA
Young
B D
BD
Rohatiner
A Z S
AZ
D000208:Acute Disease; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000235:genetics* / Q000628:therapy; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation
D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide