Haemoprotection against cytostatic drugs by stem cell inhibition.

Cytostatic drug-induced haematopoietic damage is a major problem in tumour chemotherapy, due to the intensive proliferation of many bone marrow constituents and to the drug-induced recruitment of immature pluripotent haematopoietic cells (spleen colony-forming units, CFU-S). Marie-Hélène Moser and Walter Paukovits discuss how it should be possible to minimize such proliferation-associated damage by inhibiting CFU-S during the most dangerous treatment phases, with factors such as transforming growth factor beta, tumour necrosis factor alpha, macrophage inflammatory protein 1 alpha, and the CFU-S-inhibitory peptides N-acetyl-Ser-Asp-Lys-Pro and pyroGlu-Glu-Asp-Cys-Lys (pEEDCK). Clinically relevant data are available for pEEDCK, showing that application of this peptide leads to a delayed, shorter, and less severe neutropenia, combination of pEEDCK with a stimulator avoids neutropenia, and stem cell preservation with pEEDCK improves long-term reconstitution of the haematopoietic system. Stem cell inhibition by synthetic peptides like pEEDCK may provide a useful strategy for bone marrow protection.