Leukemia following Hodgkin's disease.

To investigate the effect of different treatments for Hodgkin's disease on the risk of leukemia, we used an international collaborative group of cancer registries and hospitals to perform a case-control study of 163 cases of leukemia following treatment for Hodgkin's disease. For each case patient with leukemia, three matched controls were chosen who had been treated for Hodgkin's disease but in whom leukemia did not develop. The use of chemotherapy alone to treat Hodgkin's disease was associated with a relative risk of leukemia of 9.0 (95 percent confidence interval, 4.1 to 20) as compared with the use of radiotherapy alone. Patients treated with both had a relative risk of 7.7 (95 percent confidence interval, 3.9 to 15). After treatment with more than six cycles of combinations including procarbazine and mechlorethamine, the risk of leukemia was 14-fold higher than after radiotherapy alone. The use of radiotherapy in combination with chemotherapy did not increase the risk of leukemia above that produced by the use of chemotherapy alone, but there was a dose-related increase in the risk of leukemia in patients who received radiotherapy alone. The peak in the risk of leukemia came about five years after chemotherapy began, and a large excess persisted for at least eight years after it ended. After adjusting for drug regimen, we found that patients who had undergone splenectomy had at least double the risk of leukemia of patients who had not, and an advanced stage of Hodgkin's disease carried a somewhat higher risk of leukemia than Stage I disease. We conclude that chemotherapy for Hodgkin's disease greatly increases the risk of leukemia and that this increased risk appears to be dose-related and unaffected by concomitant radiotherapy. In addition, the risk is greater for patients with more advanced stages of Hodgkin's disease and for those who undergo splenectomy.