Two hundred patients treated with curative intent for
Hodgkin's disease between October 1964 and April 1984 at a single institution were studied retrospectively for development of
second malignancies. The minimum follow-up was 2 years (median, 11 years). The staging distribution was IA-B, 61; IIA, 54; IIB, 20; IIIA, 46; and IIIB, 19. Sixty-one percent of the patients had
laparotomy. Initial management was irradiation alone (RA) in 143 patients and a combination of
chemotherapy and irradiation (CB) in 57 patients. Actuarial 10-year survival rates were 82%, IA-B; 78%, IIA; 66%, IIB; 66%, IIIA; and 24%, IIIB. Cause-specific deaths due to
Hodgkin's disease or complications of initial or
salvage therapy occurred in 3% of IA-B patients, 18% of IIA-B patients, and 35% of IIIA-B patients. One patient had a prior T3N1
squamous cell carcinoma of the retromolar trigone, and a second was diagnosed with concurrent
Hodgkin's disease and
granulocytic sarcoma. Subsequent solid
tumors have occurred in six patients from 5 to 21 years
after treatment, including
papillary carcinoma of the thyroid,
renal cell carcinoma, unilateral
breast carcinoma, cervix
carcinoma in situ, and lung
carcinoma after RA, and bilateral
breast carcinoma after CB. Seven fatal hematopoietic disorders (HPDs) were observed, including four acute
leukemias, one dysmyeloproliferative syndrome (
DMPS), one
autoimmune hemolytic anemia, and one
aplastic anemia. Two occurred in patients initially managed with RA who subsequently required
chemotherapy for relapse. Five HPDs occurred in patients initially managed with CB who never relapsed. All HPDs were observed between 2 and 7.5 years after administration of
chemotherapy. Statistical analysis of the data using a rerandomization test on Gehan ranks of treatment and clinical variables showed significant correlations between development of a secondary HPD and (1) initial management with CB; (2) higher doses of
chemotherapy; and (3) more advanced disease, particularly IIIB. When only the five events generally associated with treatment (i.e. the four
leukemias and one
DMPS) were considered, there was a significant correlation with exposure to
chemotherapy and presentation with advanced disease. The patient population was small so that interdependence between treatment factors and initial extent of disease in affecting the risk of a secondary HPD cannot be discounted but should be further investigated with larger patient populations.