The use of
combined modality therapy (irradiation and combinations of drugs) in the treatment of
Hodgkin's disease has produced a significant improvement in survival, during which most patients lead an active and productive life. The estimated 1% incidence of
leukemia in treated
Hodgkin's disease patients, however, is greater than would be expected in the general population. There is a vast amount of literature which indicates that
alkylating agents,
procarbazine and irradiation are leukemogenic and immunosuppressive in animals and man. It is than conceivable that the current intensive treatment programs which use these agents are promoting the development of acute non-
lymphocytic leukemia (
ANLL). This
leukemia has occurred most often in patients whose
Hodgkin's disease is poorly controlled and who have received more aggressive
therapy. The latent period from the diagnosis of
Hodgkin's disease to the diagnosis of
leukemia is significantly shorter (p less than .0005) in those patients who have received intensive and near maximal
radiotherapy (total nodal irradiation),
combination chemotherapy (MOPP or equivalent) or a sequential combination of the two modalities than similar patients who were treated with less than total nodal irradiation and or single agent
chemotherapy. The following characteristic features have occurred with sufficient frequency to suggest that the subsequent
leukemia is a distinct clinicopathological entity:
pancytopenia, megaloblastoid marrow, nucleated red blood cells in the peripheral blood, random
chromosomal aberrations of the bone marrow in most patients (94%), and refractoriness to antileukemia
therapy (response rate 6.5%) with a very short survival (median one month).