BIOLOGIC RHYTHMS IN HEMATOLOGY

The number of circulating blood cells and their function, as expressed by phagocytosis, the response to mitogens or by the natural killer ce ll activity, and the formation of blood cells in the bone marrow, and their response to toxic (e.g. chemotherapeutic) agents show biologic r hythms in several frequencies of which the circadian rhythms are most extensively explored. Some of these rhythms show large enough amplitud es to be clinically important, especially if consecutive samples of th e same patients are to be evaluated. Rhythm disturbances characterize hematologic and immune related disease states like, e.g., infection wi th HIV; Circadian rhythms in the aggregability and adhesiveness of blo od platelets contribute to the transient state of hypercoagulability d uring the morning hours which is thought to lead to the peak incidence at this time of myocardial infarction, cerebral infarct, and sudden c ardiac death. The rhythmic, and thus in their timing to a certain degr ee, predictable changes in responsiveness of the hematopoietic and imm une system provide an opportunity to improve the effects of growth fac tors and cytokines, and decrease their undesirable side effects. Timin g of cancer chemotherapy at the time of maximal resistance of the hema topoietic system to a certain drug may improve the often dose limiting toxicity of the agent. Some preliminary results suggest that not only treatment toxicity may be diminushed, but also efficacy may be improv ed. This approach is made difficult by the large individual difference s in the timing of the rythms, and by the interaction of circadian, ci rcaseptan, and circannual rhythms which have, thus far, been only inco mpletely explored.