The applied therapy affects disease and patient leading to treatment failure or cure, and side effects, respectively. This in term may lead to therapy changes. For drugs with high therapeutic indices, therapy modifications is mainly determined by the response of the disease, whereas for drugs with low therapeutic indices, feedback through both the therapy-patient axis and the therapy-patient axis is likely to modify the therapy. Patient and disease interact directly via immune responses, bone marrow stroma support of leukemia, and suppression of hematopoesis etc. In addition to affecting the therapy-patient interaction, the patient's pharmacogenetic profile affects the therapy-disease axis through its effect on drug clearance, metabolism, distribution etc.