Epipodophyllotoxins, alkylating agents, and radiation and risk of secondary leukaemia after childhood cancer.
OBJECTIVE
To investigate the incidence and aetiology of secondary leukaemia after childhood cancer in Britain.


METHODS
Cohort study and a case-control study.


METHODS
Britain and population based National Register of Childhood Tumours.


METHODS
Cohort of 16,422 one year survivors of childhood cancer diagnosed in Britain between 1962 and 1983, among whom 22 secondary leukaemias were observed. A case-control study of 26 secondary leukaemias observed among survivors of childhood cancer diagnosed in Britain between 1940 and 1983; 96 controls were selected matched for sex, type of first cancer, age at first cancer, and interval to diagnosis of secondary leukaemia.


METHODS
Dose of radiation averaged over patients' active bone marrow and total accumulated dose of epipodophyllotoxins, alkylating agents, vinca alkaloids, antimetabolites, and antibiotics (mg/m2) given for the original cancer.


RESULTS
Cumulative risk of secondary leukaemia within the cohort did not exceed 0.5% over the initial five years beyond one year survival, except that after non-Hodgkin's lymphomas 1.4% of patients developed secondary leukaemia. Corresponding figure for patients treated for non-Hodgkin's lymphomas in the early 1980s was 4%. The relative risk of secondary leukaemia increased significantly with exposure to epipodophyllotoxins and dose of radiation averaged over patients' active bone marrow. Ten patients developed leukaemia after having an epipodophyllotoxin-teniposide in nine cases, etoposide in one. Chromosomal translocations involving 11q23 were observed relating to two secondary leukaemias from a total of six for which there were successful cytogenetic studies after administration of an epipodophyllotoxin.


CONCLUSIONS
Epipodophyllotoxins acting alone or together with alkylating agents or radiation seem to be involved in secondary leukaemia after childhood cancer.
Hawkins
M M
MM
Childhood Cancer Research Group, University of Oxford.
Wilson
L M
LM
Stovall
M A
MA
Marsden
H B
HB
Potok
M H
MH
Kingston
J E
JE
Chessells
J M
JM
D000477:Alkylating Agents / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007938:Leukemia / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000209:etiology*; D011034:Podophyllotoxin / Q000009:adverse effects*; D011878:Radiotherapy / Q000009:adverse effects*; D012307:Risk Factors
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D011034:Podophyllotoxin