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 cell activity, and the formation of blood cells in the bone marrow, and their response to toxic (e.g. chemotherapeutic) agents show biologic rhythms in several frequencies of which the circadian rhythms are most extensively explored. Some of these rhythms show large enough amplitudes to be clinically important, especially if consecutive samples of the same patients are to be evaluated. Rhythm disturbances characterize hematologic and immune related disease states like, e.g., infection with HIV. Circadian rhythms in the aggregability and adhesiveness of blood platelets contribute to the transient state of hypercoagulability during the morning hours which is thought to lead to the peak incidence at this time of myocardial infarction, cerebral infarct, and sudden cardiac death. The rhythmic, and thus in their timing to a certain degree, predictable changes in responsiveness of the hematopoietic and immune system provide an opportunity to improve the effects of growth factors and cytokines, and decrease their undesirable side effects. Timing of cancer chemotherapy at the time of maximal resistance of the hematopoietic 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 diminished, but also efficacy may be improved. This approach is made difficult by the large individual differences in the timing of the rhythms, and by the interaction of circadian, circaseptan, and circannual rhythms which have, thus far, been only incompletely explored.