Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.

The prognostic score we developed may be useful in designing clinical trials for the treatment of advanced Hodgkin's disease and in making individual therapeutic decisions, but a distinct group of patients at very high risk could not be identified on the basis of routinely documented demographic and clinical characteristics.

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.

Combined modality treatment in patients with advanced-stage Hodgkin's disease overall has a significantly inferior long-term survival outcome than CT alone if CT is given over an appropriate number of cycles. The role of RT in this setting is limited to specific indications.

The objective of this study was to design and validate a bedside decision instrument to be used by patients with chronic myeloid leukemia and their physicians in deciding between the therapeutic alternatives of bone marrow transplantation and conservative management during the early phase of disease. A decision board was constructed containing detailed scenarios associated with the treatment alternatives, together with estimates of survival probabilities at various periods of followup. The instrument was tested on 42 healthy hospital personnel and validated by measuring the extent to which systematic alterations in the scenarios with respect to toxicities and survival probabilities produced predicted shifts in treatment preferences. A subgroup of respondents was randomized to receive information through the decision board alone or a shorter and less informative version of the instrument, followed by the decision board. The direction and strength of stated preferences were compared, together with satisfaction for these preferences. The direction and strength of preferences between bone marrow transplantation or conservative chemotherapy were influenced in a predictable way by changes in the toxicity and survival descriptions in the scenarios. Using the test-retest method in 16 subjects, the stated preferences were found to be highly reliable (intraclass correlation coefficient, 0.87). The mean level of satisfaction with the stated preference, on a scale from not at all satisfied = 1 to very satisfied = 5, was higher for those exposed to the decision board (3.7, SD 1.06) compared with those presented with the short version (2.95, SD 0.67) (P < 0.01). The results demonstrate the feasibility and acceptability of the instrument in healthy individuals. The preferences elicited by the instrument appear to be reliable and valid according to prespecified constructs of the relation between the information provided and the preferences predicted. These results support further testing of this approach in actual patients.