Long term hematopoietic damage after chemotherapy and cytokine.

Cancer chemotherapy causes severe damage to hematopoietic stem cells in both experimental animals and humans. While all levels of differentiation may be impacted, the most pivotal target of damage is the most primitive hematopoietic stem cell, PHSC. This cell not only suffers defective repopulating activity but also is quantitatively depleted. The causes of this damage are not clear. Severe possible explanations for this damage are discussed. They include: ineffective stromal support of stem cell function and reproduction; residual DNA damage preventing replication; accelerated cycling; and decreased responsiveness to normal physiologic growth stimuli. Efforts at chemoprotection, including manipulation of glutathione or aldehyde dehydrogenase levels, cytostatic peptides, immunomodulatory chemicals and cytokines are detailed. In particular, concern has been raised regarding potential deleterious consequences of combined chemotherapy-cytokine use, but substantiation of the cited data is warranted.