Risk of secondary acute leukemia and preleukemia after Hodgkin's disease: the Institut Gustave-Roussy experience.
From 1960 to 1984, 871 patients were treated for Hodgkin's disease at the Institut Gustave-Roussy. Twenty-six percent of the cohort were treated with radiotherapy (RT) alone, 6% with chemotherapy (CT) alone, and 68% with a combination of RT and CT, either at first line or for salvage treatment. MOPP chemotherapy was given to 42% of the patients. Overall, 19 secondary acute leukemias or preleukemias were observed, 3 of them after extended RT alone, the other 16 after a combination of RT and MOPP. Among the alkylating agents used, only nitrogen mustard (mechloretamine) was shown in a multivariate analysis to be significantly associated (P less than 0.001) with an increased risk of secondary leukemia. A dose response was observed, with the risk relative to general population incidence rates being 45 in patients having been treated with 1-59 mg (total dose) of nitrogen mustard, 211 in those treated with 60-119 mg, and 636 in those treated with greater than or equal to 120 mg. No other factors were found to be associated with leukemia risk. The 10-year cumulative incidence of leukemia was zero in patients treated with limited RT alone, 2.4% in those treated with extended RT alone, 0% in those treated with a combination of RT and CT without nitrogen mustard, and 12.4% in those treated with RT + nitrogen mustard. Whether other alkylating agents give a similar result remains to be determined; these data suggest that the use of nitrogen mustard at a higher total dose than 60 mg is questionable in the treatment of Hodgkin's disease.
Henry-Amar
M
M
Institut Gustave-Roussy, Villejuif, France.
Pellae-Cosset
B
B
Bayle-Weisgerber
C
C
Hayat
M
M
Cosset
J M
JM
Carde
P
P
Tubiana
M
M
D000328:Adult; D000367:Age Factors; D000477:Alkylating Agents / Q000009:adverse effects; D005260:Female; D006689:Hodgkin Disease / Q000150:complications* / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011289:Preleukemia / Q000209:etiology*; D012307:Risk Factors; D012737:Sex Factors; D013156:Splenectomy
D000477:Alkylating Agents