The problem of permanent bone marrow damage after cytotoxic drug treatment

The majority of cytotoxic drugs exert a dose-dependent injury to the hemopoietic bone marrow. In experimental systems, two different types of damage to the hemopoietic stem cell compartments have been demonstrated to occur following cytotoxic drug exposure. First, a reversible reduction of the size of these stem cell compartments; recovery of compartment size results from a transiently increased proliferative activity of those stem cells surviving the cytotoxic drug exposure. Second, irreversibly decreased proliferative potential of pluripotent stem cells has been observed after some cytotoxic agents. Experimental evidence indicates that such permanent stem cell damage may lead to the failure of the hemopoietic bone marrow to produce sufficient numbers of blood cells. There are indications that a similar permanent damage to the hemopoietic system may occur in man following repeated exposure to at least some cytotoxic agents.